sirolimus and Coronary-Restenosis

A drug-eluting balloon is a non-stent technology in which the effective homogenous delivery of anti-proliferative drugs is processed by the vessel wall through an inflated balloon. This is done to restore luminal vascularity in order to treat atherosclerosis, in-stent restenosis and reduce the risk of late thrombosis without implanting a permanent foreign object. The balloon technology relies on the concept of targeted drug delivery, which helps in the rapid healing of the vessel wall and prevents the proliferation of smooth muscle cells. Several drug eluting devices in the form of coated balloons are currently in clinical use, namely DIOR

Topics: Angioplasty, Balloon; Animals; Atherosclerosis; Brachytherapy; Coated Materials, Biocompatible; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; Lasers; Materials Testing; Paclitaxel; Polymers; Prosthesis Design; Sirolimus; Treatment Outcome

The novel dual-therapy COMBO stent aims to promote vessel healing after percutaneous coronary intervention (PCI) in patients with coronary artery disease. The pro-healing technique consists of an anti-CD34+ antibody layer that attracts circulating endothelial progenitor cells (EPCs), which bind to the stent surface and allow rapid endothelialization by differentiation of the EPCs into normal endothelial cells. The COMBO stent combines this pro-healing technique with an abluminal drug elution of sirolimus. The promise of this dual-therapy stent is that it may safely allow a shortened duration of dual-antiplatelet therapy (DAPT) after stent placement. Moreover, with a mature endothelial layer, lower rates of in-stent restenosis may be expected. Clinical outcomes after COMBO stent implantation have been recently evaluated in both randomized trials and large, prospective, multicenter registries, showing low clinical event rates of in-stent restenosis and stent thrombosis. Randomized clinical trials (HARMONEE and RECOVERY) have demonstrated the non-inferiority of COMBO versus "first in class" second generation and newer generation drug-eluting stents. Safety and efficacy of 3 months of DAPT after COMBO stent placement in patients presenting with acute coronary syndrome has been evaluated in the large REDUCE randomized controlled trial, showing non-inferiority to standard duration of 12-month DAPT. In this review we provide an overview of the current pre-clinical and clinical evidence for the performance of the COMBO stent.

Topics: Acute Coronary Syndrome; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Endothelial Progenitor Cells; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Sirolimus

The present manuscript reviews the mechanism of action of drug-coated balloons (DCBs), offering a brief summary of the main clinical evidence on these devices.. DCBs are regular semi-compliant balloons coated with antiproliferative agents that are rapidly released on contact with the vessel intima, exerting an anti-restenotic effect. This technology may offer some benefits of drug-eluting stents, in particular for the treatment of restenotic lesions, small vessels, and in patients at high-bleeding risk, when the prolonged dual antiplatelet regimen should be avoided. Most recent data have pointed to a possible benefit of these devices in treating bare metal stents (BMS) or drug-eluting stents in-stent restenosis (DES ISR), effectively reducing the recurrence of restenosis and avoiding additional layers of metal in the same coronary segment. In other clinical scenarios such as bifurcations, small vessels, and de novo lesions, data is more scarce and the benefits are still unclear. There are potential benefits related to the use of DCB in selected populations. However, larger clinical trials with longer follow-up are still needed to confirm the enthusiastic initial results.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Equipment Failure; Foreign-Body Migration; Humans; Neointima; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

Treatment of coronary artery disease has made strides over the last decades. Development of drug eluting stents (DES), coated with a polymer layer and an anti-proliferative drug to reduce neointimal hyperplasia, has reduced the incidence of in-stent-restenosis relative to treatment with bare metal stents. Patients treated with first generation DES more likely suffer from (very) late events which can be cause by the permanent presence of a polymer. Therefore second generation DES with more biocompatible coatings, and third generation DES, with very thin struts coated with biodegradable polymers, were developed. Areas covered: The MiStent SES is one of these third generation DES and is designed to limit the duration of polymer exposure, optimize coronary vessel healing and more precisely and consistently control drug elution to improve safety and clinical outcomes. This review provides a detailed description of the technique behind the MiStent SES, and describes the pre-clinical and clinical trials conducted with this device to date. Expert commentary: Recent clinical trials have shown non-inferiority of very thin strut biodegradable polymer coated DES compared to durable polymer coated DES, whilst maintaining an excellent safety profile. Longer follow-up, to see the real potential benefits of these devices, is mandatory however.

Topics: Absorbable Implants; Animals; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Drug Implants; Drug Liberation; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Polymers; Propensity Score; Prosthesis Design; Sirolimus; Swine; Time Factors; Treatment Outcome

Drug-eluting balloons (DEB) may be considered as a 'quiet revolution' in percutaneous coronary interventions. Early-generation DEB eluting paclitaxel proved to be very effective in animal models to reduce neointimal hyperplasia. Areas covered: Review of DEB efficacy in patients with coronary de novo lesions and in-stent restenosis (ISR). Expert opinion: Many randomized clinical trials and meta-analyses have demonstrated the value of DEB in patients with ISR. In this setting, DEB are safe and effective with clinical and angiographic results superior to plain balloon angioplasty and at least equivalent to first generation drug-eluting stents (DES). In selected 'de novo' lesions (bifurcation lesions, small vessels, diffuse disease, myocardial infarction) DEB represent an attractive alternative although additional evidence in these 'niche' indications is still required before a widespread clinical utilization can be recommended. Recently, new generation DEB have become available, offering interesting new possibilities (paclitaxel and also sirolimus) for coronary interventions. Further studies are required to compare the results of novel generation DEB with those of second-generation DES.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome; Tubulin Modulators

Although first-generation drug-eluting stents (DES) have significantly reduced the risk of in-stent restenosis, they have also increased the long-term risk of stent thrombosis. This safety concern directly triggered the development of new generation DES, with innovations in stent platforms, polymers, and anti-proliferative drugs. Stent platform materials have evolved from stainless steel to cobalt or platinum-chromium alloys with an improved strut design. Drug-carrying polymers have become biocompatible or biodegradable and even polymer-free DES were introduced. New limus-family drugs (such as everolimus, zotarolimus or biolimus) were adopted to enhance stent performances. As a result, these new DES demonstrated superior vascular healing responses on intracoronary imaging studies and lower stent thrombotic events in actual patients. Recently, fully-bioresorbable stents (scaffolds) have been introduced, and expanding their applications. In this article, the important concepts and clinical results of new generation DES and bioresorbable scaffolds are described.

Topics: Absorbable Implants; Coated Materials, Biocompatible; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Inventions; Percutaneous Coronary Intervention; Polymers; Postoperative Complications; Randomized Controlled Trials as Topic; Sirolimus; Thrombosis

Drug-eluting stents (DES) have dramatically improved the long-term efficacy of percutaneous coronary intervention (PCI). Over the last decade there have been numerous advances in DES platforms, however, all but one currently approved DES in the United States and many of the approved DES worldwide still have 3 common features: a metal stent platform, an anti-proliferative drug, and a permanent polymer. In this context, the polymer is critical to control drug release, but the polymer serves no purpose after the drug is eluted. While designed to be completely biocompatible, synthetic polymers have the potential to illicit an inflammatory response within the vessel including but not limited to delayed healing and hypersensitivity. Adverse vascular reactions to these polymers have been implicated as a cause of very late stent thrombosis, ongoing intimal hyperplasia and late "catch-up" in addition to neoatherosclerosis. To avoid the long-term risks associated with prolonged polymer exposure, DES with bioabsorbable polymers have been developed. The MiStent® Sirolimus-Eluting Absorbable Polymer Coronary Stent System (MiStent SES) (MiCell Technologies, Durham, NC, USA) combines crystalline sirolimus, a rapidly absorbing polylactide-co-glycolic acid (PLGA) coating and a thin-strut cobalt chromium alloy stent platform (Genius MAGIC® Stent System, EuroCor GmbH, Germany). MiCell's supercritical fluid technology allows a rigorously controlled, solvent-free drug and polymer coating to be applied to a bare-metal stent. This solvent-free application of drug uniquely allows a crystalline form of sirolimus to be used on the MiStent SES potentially providing improved clinical benefits. It avoids the uncontrolled burst of drug seen with other DES, provides uniform drug delivery around and between the stent struts, and allows the anti-inflammatory and anti-restenotic drug (sirolimus) to be present in the tissue through the entire polymer absorption period and for months after the polymer has been absorbed. On the MiStent SES, the PLGA/crystalline sirolimus combination is cleared from the stent within 45-60 days and PLGA is fully absorbed within 90 days. The crystalline form of sirolimus uniquely remains in the tissue and continues to expose the surrounding tissue to therapeutic levels of drug for up to 9 months which is long after the polymer is resorbed.

Topics: Absorbable Implants; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus

Device technology in interventional cardiology is continuously evolving. Self-expandable (SE) coronary artery stents were the first device to be implanted within a human coronary artery. However, because of their initial limitations, balloon-expandable (BE) stents were predominantly developed and used in the last 30 years. Unfortunately, in challenging anatomical settings such as bifurcation lesions, large, ectatic or aneurysmal vessels, tapered vessels or vasoconstricted arteries, outcomes with BE stents are not always optimal. The Stentys (Stentys SA, Paris, France) SE nitinol stents were initially developed for the treatment of coronary bifurcation lesions. The understanding of the underlying mechanism involved in incomplete stent apposition and subsequent stent thrombosis led to the introduction of self-apposing stents in the treatment of acute coronary syndrome in order to overcome the limitations of drug-eluting stents in presence of high thrombus burden. In this regard, Stentys allows a progressive stent expansion which could reduce the rates of incomplete stent apposition by conforming to vascular remodeling. Enhancing the advantages of this technology by adding the release of an antiproliferative drug to prevent restenosis is even more attractive and potentially effective. Recently, the results of the new Stentys sirolimus-eluting stent have been reported. This article provides an overview of the pathobiological rational, device characteristics and results of the new Stentys self-expandable sirolimus-eluting stent.

Topics: Acute Coronary Syndrome; Alloys; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus

Compared with the zotarolimus-eluting stent (ZES), the everolimus-eluting stent (EES) has reduced the risk of stent restenosis and thrombosis as found in a number of randomized-controlled trials (RCTs). However, the benefits have been variable.. We evaluate the long-term effect of EES and ZES on the risk of stent thrombosis and target lesion revascularization in patients receiving PCI. We identified RCTs by a systematic search of MEDLINE, EMBASE, and Cochrane Database.. Five RCTs (9853 patients) were included. Overall, EES significantly reduced the risk of target lesion revascularization [odds ratio (OR), 0.77; 95% confidence interval (CI), 0.62-0.95; P=0.01] compared with ZES therapy. However, there was no difference in the risk of target vessel revascularization (OR, 0.93; 95% CI, 0.78-1.10; P=0.38) and definite/probable stent thrombosis (OR, 0.83; 95% CI, 0.56-1.25; P=0.37) between the two groups. Furthermore, the risk of mortality (OR, 1.04; 95% CI, 0.84-1.27; P=0.73), myocardial infarction (OR, 0.95; 95% CI, 0.74-1.23; P=0.70), and major adverse cardiac event (OR, 0.96; 95% CI, 0.84-1.10; P=0.53) was similar between the two groups.. The new-generation Resolute-ZES and EES have a similar long-term safety and efficacy profile.

Topics: Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Percutaneous coronary intervention (PCI) has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stent (BMS) and then first- and second-generation drug-eluting stents (DES) have enhanced the results of PCI by improving early results and reducing the risk of restenosis and stent thrombosis (ST). The delay of re-endothelialization and recovery of endothelial function after stenting as well as inhibition of vascular repair after DES implantation, in part related to permanent polymers, are consider important part of ST pathophysiology mechanism. Several progresses have been made to overcome this issue, among them the development of new more biocompatible - first - and completely biodegradable - then - polymer coatings. A third-generation DES using a biodegradable polymer and eluting sirolimus (Ultimaster®, Terumo Corporation, Tokyo, Japan) has been recently introduced to overcome the long-term adverse vascular reactions. Thanks to the polymer coating applied to the outside surface only (abluminal side), the total drug dose applied on the stent platform has been reduced, leaving the luminal side of the stent free from drug and polymer to enhance endothelial coverage. Indeed, 3-4 months after implantation, the Ultimaster® DES has lost most of its coating, acquiring a profile similar to conventional BMS. This article reviews the recent publications investigating the safety and effectiveness of the bioresorbable polymer sirolimus-eluting Ultimaster® stent (BP-SES), for the treatment of coronary artery lesions.

Topics: Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Polymers; Sirolimus; Thrombosis; Time Factors

Coronary atherosclerosis often involves small-caliber coronaries, yet the safety and efficacy of 2.25-mm DES have been poorly defined, with a general lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head 2.25 mm DES studies have been reported. There are several single-arm prospective studies, and we aim to systematically review all published specific 2.25-mm data to estimate composite DES-specific performance and highlight current knowledge gaps.. We performed a systematic literature search of PubMed, EMBASE, Web of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic and composite clinical outcomes were compared with descriptive statistics.. 2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum chromium EES DES-specific outcomes have been reported. Death at 12 months for SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of target vessel revascularization at 12 months for SES, PES, EES and platinum chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was 0.15 ± 0.11-mm, 0.28 ± 0.11-mm, and 0.16 ± 0.41-mm and mean diameter restenosis for SES, PES, and EES were 29.5 ± 6.2%, 34.7 ± 4.2%, and 20.9 ± 22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0% to 2.2% in up to 24-months of follow-up.. This systematic review summarizes and tabulates all available specific data on 2.25-mm DES. Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions.

Topics: Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Sirolimus

Drug-eluting stents (DES) have become more widely used by cardiologists than bare metal stents (BMS) because of their better ability to control restenosis. However, recognized negative events, particularly including delayed or incomplete endothelialization and late stent thrombosis, have caused concerns over the long-term safety of DES. Although stent-based drug delivery can facilitate a drug's release directly to the restenosis site, a burst of drug release can seriously affect the pharmacological action and is a major factor accounting for adverse effects. Therefore, the drug release rate has become an important criterion in evaluating DES. The factors affecting the drug release rate include the drug carrier, drug, coating methods, drug storage, elution direction, coating thickness, pore size in the coating, release conditions (release medium, pH value, temperature), and hemodynamics after the stent implantation. A better understanding of how these factors influence drug release is particularly important for the reasonable use of efficient control strategies for drug release. This review summarizes the factors influencing the drug release from DES and presents strategies for enhancing the control of the drug's release, including the stent design, the application of absorbable stents, the development of new polymers, and the application of nanocarriers and improvements in the coating technology. Therefore, this paper provides a reference for the preparation of novel controlled slow-release DES.

Topics: Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; Prosthesis Design; Sirolimus

Restenosis following vascular revascularization remains an important clinical problem. Local drug delivery which can provide enough drug concentration in the lesion location without causing adverse systemic effect is an excellent solution for this question. We conducted a systematic literatory search on PubMed and CKNI through May 2014. After reviewing all related papers, we provided a comprehensive overview of the available drugs and techniques for local drug delivery that have been developed to prevent restenosis after peripheral vascular interventions, including innovations that have been tested only in animals as well as those already approved for clinical use. In brief, anti-proliferative drugs such as paclitaxel and sirolimus are the most used and suitable drugs for local delivery system. Additionally, some promising drugs including anti-inflammatory drugs, antioxidant drugs and drugs inhibiting cell proliferation and migration are already being tested in pre-clinical trials or animal models. At the same time, intraluminal and extraluminal delivery devices have also got a rapid development during the past decades. The efficacy of drug-eluting stent, drug-eluting balloon, porous and microporous balloon and the most recent drug-eluting bioresobable scaffold for preventing of restenosis in peripheral vessels have been demonstrated in humans or in animals, some of them even have received the CE mark in Europe. Endovascular microinfusion catheter and drug-loaded perivascular wraps have only been tested in animal models, more researches are needed. With the development of pharmacology and bioengineering, great strides will be made in the prevention of restenosis in the near future.

Topics: Animals; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Arteries; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; Myocardial Revascularization; Paclitaxel; Sirolimus

Percutaneous coronary intervention (PCI) with drug-eluting stents is the standard of care for treatment of native coronary artery stenoses, but optimum treatment strategies for bare metal stent and drug-eluting stent in-stent restenosis (ISR) have not been established. We aimed to compare and rank percutaneous treatment strategies for ISR.. We did a network meta-analysis to synthesise both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomised controlled trials published up to Oct 31, 2014, of different PCI strategies for treatment of any type of coronary ISR. The primary outcome was percent diameter stenosis at angiographic follow-up. This study is registered with PROSPERO, number CRD42014014191.. We deemed 27 trials eligible, including 5923 patients, with follow-up ranging from 6 months to 60 months after the index intervention. Angiographic follow-up was available for 4975 (84%) of 5923 patients 6-12 months after the intervention. PCI with everolimus-eluting stents was the most effective treatment for percent diameter stenosis, with a difference of -9·0% (95% CI -15·8 to -2·2) versus drug-coated balloons (DCB), -9·4% (-17·4 to -1·4) versus sirolimus-eluting stents, -10·2% (-18·4 to -2·0) versus paclitaxel-eluting stents, -19·2% (-28·2 to -10·4) versus vascular brachytherapy, -23·4% (-36·2 to -10·8) versus bare metal stents, -24·2% (-32·2 to -16·4) versus balloon angioplasty, and -31·8% (-44·8 to -18·6) versus rotablation. DCB were ranked as the second most effective treatment, but without significant differences from sirolimus-eluting (-0·2% [95% CI -6·2 to 5·6]) or paclitaxel-eluting (-1·2% [-6·4 to 4·2]) stents.. These findings suggest that two strategies should be considered for treatment of any type of coronary ISR: PCI with everolimus-eluting stents because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer.. None.

Topics: Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Myocardial Revascularization; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

The advent of fully bioresorbable stent technology and specifically the ABSORB™, a bioresorbable vascular scaffold (BVS) stent, is heralded as breakthrough technology in the current era of percutaneous coronary interventions. This article reviews the current understanding of this technology along with the clinical evidence from trials and registries of ABSORB BVS that included patients with both simple as well as more complex "real-world" coronary lesions. In addition, considering the current limitations of this device-mostly associated with the mechanical properties of the polymeric scaffold structure-a review of guidelines on successful implantation of the ABSORB BVS is presented. Although expert feedback suggests extensive use of this device in routine clinical practice outside the United States despite a paucity of data on long-term safety in this setting, attention to procedural details and implantation technique is obligatory to achieve optimal clinical outcomes.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Evidence-Based Medicine; Female; Follow-Up Studies; Humans; Male; Prosthesis Design; Risk Assessment; Severity of Illness Index; Sirolimus; Survival Analysis; Time Factors; Tissue Scaffolds; Treatment Outcome

In-stent restenosis (ISR) remains a difficult problem in interventional cardiology. The relative efficacy and safety of available interventions is not clear. We aimed to perform a network meta-analysis using both direct evidence and indirect evidence to compare all available interventions.. We systematically searched electronic databases for randomized trials comparing ≥2 treatments for ISR. A network meta-analysis was performed using a Bayesian approach. Eleven treatments were compared in 31 studies with 8157 patient-years follow-up. Compared with balloon angioplasty, everolimus-eluting stent (hazard ratio [95% credibility interval], 0.13 [0.048-0.35]), paclitaxel-eluting balloon (0.32 [0.20-0.49]), paclitaxel-eluting cutting balloon (0.054 [0.0017-0.5]), paclitaxel-eluting stent (0.39 [0.24-0.62]), and sirolimus-eluting stent (0.32 [0.18-0.50]) are associated with lower target vessel revascularization. Balloon angioplasty is not different from cutting balloon (0.73 [0.31-1.5]), excimer laser (0.89 [0.29-2.7]), rotational atherectomy (0.96 [0.53-1.7]), and vascular brachytherapy (0.60 [0.35-1.0]). In drug-eluting stent ISR, balloon angioplasty was inferior to everolimus-eluting stent (0.19 [0.049-0.76]), paclitaxel-eluting balloon (0.43 [0.18-0.80]), paclitaxel-eluting stent (0.35 [0.13-0.76]), and sirolimus-eluting stent (0.36 [0.11-0.86]) for target vessel revascularization. There was no difference between treatments in probable or definitive stent thrombosis. The results of binary restenosis and target lesion revascularization were similar. Paclitaxel-eluting cutting balloon, everolimus-eluting stent, and paclitaxel-eluting balloon have the highest probability of being in the top 3 treatments based on low target lesion revascularization, but there was no statistical significant difference between them.. Balloon angioplasty is inferior to all drug-eluting treatments for ISR, including drug-eluting stent ISR. Drug-eluting stent, particularly everolimus-eluting stent, or paclitaxel-eluting cutting balloon and paclitaxel-eluting balloon should be preferred for treating ISR.

Topics: Angioplasty, Balloon; Blood Vessel Prosthesis Implantation; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Percutaneous Coronary Intervention; Postoperative Complications; Proportional Hazards Models; Randomized Controlled Trials as Topic; Sirolimus

Our aim was to evaluate the five-year clinical impact of side branch (SB) stenting with a drug-eluting stent (DES) following Axxess stent implantation in coronary bifurcation lesions.. Four hundred patients treated with Axxess were pooled from the AXXESS Plus and DIVERGE five-year follow-up studies. We compared unadjusted and propensity-adjusted major adverse clinical events (MACE) between Axxess with no SB stenting ("Axxess provisional") versus Axxess with SB stenting ("Axxess additional"). "Axxess additional" had no impact on the MACE rate, with unadjusted and adjusted HR 1.59 (95% CI: 0.95-2.64) and 1.37 (95% CI: 0.88-2.13), respectively. No differences were seen in the individual components of death, myocardial infarction and ischaemia-driven target lesion revascularisation, respectively, both in unadjusted (HR 0.92 [95% CI: 0.38-2.19]; HR 1.73 [95% CI: 0.78-3.82]; HR 1.65 [95% CI: 0.84-3.26]) and adjusted analysis (HR 0.92 [95% CI: 0.41-2.09]; HR 1.13 [95% CI: 0.59-2.17]; HR 1.31 [95% CI: 0.74-2.31]). No differences in definite stent thrombosis were seen with unadjusted HR 2.1 (95% CI: 0.45-9.88) and adjusted HR 1.0 (95% CI: 0.32-3.1).. Stenting the SB following Axxess implantation does not impact on long-term clinical outcomes compared to MV stenting only. The Axxess stent system offers a safe and tailored alternative for the treatment of coronary bifurcation lesions.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Propensity Score; Proportional Hazards Models; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

To establish whether technological improvements in drug-eluting stent (DES) technology introduced in second-generation (G2) DES have contributed to improving patient-focused outcomes.. We performed a systematic review of randomised clinical trials (RCT) comparing first-generation (G1) and G2 DES with a>9-month clinical follow-up. The primary endpoint for efficacy was ischaemia-driven target lesion revascularisation (ID-TLR); safety endpoints were all-cause death, myocardial infarction (MI) and stent thrombosis (ST). Sixteen RCTs involving 25,427 patients met eligibility criteria (17 comparisons). In these trials, paclitaxel (PES) and sirolimus (SES) were compared with everolimus (EES), zotarolimus (ZES) or biolimus A9 (BES) DES. G2 varied in metal alloy, strut thickness and type of drug-eluting matrix. Overall, G2 DES were associated with a 26% relative risk reduction (RRR) of MI (relative risk [RR]=0.74, 95% CI: 0.61-0.90, p=0.003) and ST (RR=0.70, 95% CI: 0.55-0.89, p=0.004), while no significant benefit was observed for ID-TLR and death. Use of 2G DES was associated with a significant reduction in the risk of ID-TLR (RR=0.66, 95% CI: 0.51-0.85, p=0.002), MI (RR=0.60, 95% CI: 0.49-0.72, p<0.001) and ST (RR=0.41, 95% CI: 0.26-0.65, p=0.001) when compared with PES. Strut thickness ≤91 µm in G2 DES was associated with a significantly lower risk of MI (RR=0.54, 95% CI: 0.51-0.86, p=0.002).. The introduction of thinner stent struts and other technological improvements made in G2 DES technology have translated into better patient outcomes. Overall, the net benefit of G2 DES over G1 DES is expressed in terms of ID-TLR and ST risk reduction but it could be masked by heterogeneities in the use of G1 comparators and the use of non-inferiority study designs in RCTs.

Topics: Antineoplastic Agents; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Patient Outcome Assessment; Percutaneous Coronary Intervention; Prosthesis Design; Randomized Controlled Trials as Topic; Sirolimus

The occurrence of stent thrombosis is one of the major obstacles limiting the long-term clinical efficacy of percutaneous coronary intervention. The anti-smooth muscle proliferation drugs coated on drug-eluting stents (DES) often indistinguishably block re-endothelialization, an essential step toward successful vascular repair, due to their nonspecific effect on endothelial cells (ECs). Therefore, identification of therapeutic targets that differentially regulate vascular smooth muscle cell (VSMC) and EC proliferation may lead to the development of ideal drugs for the next-generation DES. Our recent studies have shown that CTP synthase 1 (CTPS1) differentially regulates the proliferation of VSMC and EC after vascular injury. Therefore, CTPS1 inhibitors are promising agents for DES. In addition to CTPS1, other factors have also shown cell-specific effects on VSMC and/or EC proliferation and thus may become potential molecular targets for developing drugs to coat stents.

Topics: Coronary Restenosis; Drug-Eluting Stents; Endothelial Cells; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Sirolimus

Incomplete stent apposition (ISA) is characterized by the lack of contact of at least 1 stent strut with the vessel wall in a segment not overlying a side branch; it is more commonly found in drug-eluting stents than bare-metal stents. The accurate diagnosis of ISA, initially only possible with intravascular ultrasound, can currently be performed with higher accuracy by optical coherence tomography, which also enables strut-level assessment due to its higher axial resolution. Different circumstances related both to the index procedure and to vascular healing might influence ISA occurrence. Although several histopathology and clinical studies linked ISA to stent thrombosis, potential selection bias precluded definitive conclusions. Initial studies usually performed single time point assessments comparing overall ISA percentage and magnitude in different groups (i.e., stent type), thus hampering a comprehensive understanding of its relationship with vascular healing. Serial intravascular imaging studies that evaluated vascular response heterogeneity recently helped fill this gap. Some particular clinical scenarios such as acute coronary syndromes, bifurcations, tapered vessels, overlapping stents, and chronic total occlusions might predispose to ISA. Interventional cardiologists should be committed to optimal stent choices and techniques of implantation and use intravascular imaging guidance when appropriate to aim at minimizing acute ISA. In addition, the active search for new stent platforms that could accommodate vessel remodeling over time (i.e., self-expandable stents) and for new polymers and/or eluting drugs that could induce less inflammation (hence, less positive remodeling) could ultimately reduce the occurrence of ISA and its potentially harmful consequences.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Prognosis; Prosthesis Failure; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Survival Rate; Tomography, Optical Coherence

Percutaneous coronary intervention (PCI) with stent implantation has revolutionized the treatment of obstructive coronary artery disease. However, the main limitation of this therapy is stent failure, which is usually caused by in-stent restenosis.. The aim of this article is to critically review the literature on the prevention of in-stent restenosis focusing on drug compounds that have reached clinical testing.. The pathophysiological response following PCI includes many possible targets for antirestenosis treatment. Most notable success is seen with sirolimus (and its analogs) and paclitaxel, both of which target vascular smooth muscular cell proliferation. In view of the systemic side effects of both drugs, the high efficacy of local drug delivery methods reduced enthusiasm for systemic therapy. Cilastazol has shown benefit in restenosis reduction particularly in patients at high risk for stent failure, though further study in broader populations is warranted. Probucol showed variable results, but local drug delivery in combination with sirolimus seems promising. A hypothesized independent antirestenotic effect of pioglitazone in patients with diabetes has not been clearly demonstrated. Initial encouraging results with tranilast have not been replicated in a recent large-scale randomized trial. Colchicine and prednisone have shown promising results but require further investigation in larger clinical trials.

Topics: Anti-Bacterial Agents; Antioxidants; Cilostazol; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; ortho-Aminobenzoates; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Probucol; Sirolimus; Tetrazoles; Tubulin Modulators; Vasodilator Agents

The role of oral immunosuppressive therapy (OIT) to prevent restenosis after percutaneous coronary intervention (PCI) and stenting is still controversial. This study evaluates the impact of oral administration of prednisone or sirolimus to prevent restenosis.. We conducted a meta-analysis of trials in which PCI-patients were randomized to bare metal stents (BMS) plus OIT (BMS + OIT group) versus BMS or drug-eluting stents alone (BMS/DES group). Primary endpoints were target lesion revascularization and death/myocardial infarction (MI). Secondary endpoints were death, MI, stent thrombosis and in-stent late lumen loss. Hazard ratio and weighted geometric mean difference [95% confidence intervals] served as summary statistics.. Individual data of seven trials (1246 patients [BMS + OIT, n = 608 versus BMS/DES, n = 638] with 1456 coronary lesions) were merged. At a median follow-up of 360 days, BMS + OIT versus BMS/DES significantly reduced the risk of revascularization (0.49 [0.24-0.98], P = 0.04). In particular, BMS + OIT reduced the risk of revascularization (0.38 [0.21-0.67], P < 0.001) and late lumen loss (-0.39 mm [-0.67, -0.11], P < 0.001) as compared with BMS alone. BMS + OIT versus BMS/DES showed a similar risk of death/MI (0.67 [0.29-1.53], P = 0.34), death (0.82 [0.25-2.69], P = 0.71), MI (0.58 [0.24-1.39], P = 0.22) and stent thrombosis (0.43 [0.10-1.87], P = 0.26).. In patients undergoing PCI the use of BMS and oral immunosuppressive therapy reduces the risk of revascularization as compared with BMS alone but not as compared with DES alone, while these therapies display a similar risk of death/MI. The advantage of adding oral immunosuppressive therapy to BMS is due to a lower risk of restenosis as compared with BMS alone.

Topics: Administration, Oral; Aged; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Metals; Middle Aged; Percutaneous Coronary Intervention; Prednisone; Proportional Hazards Models; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Drug-eluting stents (DES) have transformed interventional cardiology over the past decade. Whilst their efficacy has rarely been called into question, there have been concerns over the safety of the early devices, which has prompted the development of new coronary stents. Many of these new devices have entered clinical practice, however questions remain as to whether they offer the improvements in clinical outcomes that were originally anticipated. In addition, there is a debate whether the reported high efficacy of these devices enables percutaneous coronary intervention (PCI) to be performed in patient and lesion sub-groups previous entirely the domain of the cardiac surgeon. This review paper addresses these outstanding questions.

Topics: Biocompatible Materials; Clinical Trials as Topic; Combined Modality Therapy; Comorbidity; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Diabetes Complications; Disease-Free Survival; Drug-Eluting Stents; Humans; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Polymers; Postoperative Complications; Sirolimus; Thrombolytic Therapy; Treatment Outcome

To evaluate clinical and angiographic outcomes after successful recanalization of chronic total coronary occlusion (CTO) with implantation of a long total stent length (SL).. Routine follow-up angiogram (RFUA) data after successful recanalization of CTO with a long SL are lacking.. RFUAs were performed at 6 months after successful recanalization of 106 CTOs using drug-eluting stents (DESs) with a long SL (≥ 20 mm) in 102 consecutive patients.. Mean number of stents was 3.9 ± 1.8 and mean total SL was 78 ± 32 mm (range, 23-174 mm). Sirolimus-eluting stents (SESs) were used in 100 lesions. In-stent total reocclusion occurred in 2 cases (1 SES and 1 non-SES DES). Restenosis rate was 18% in the 100 SES subgroup (total SL, 79 ± 33 mm; range, 23-174 mm; mean number of stents, 3.9 ± 1.8); younger age and longer total SL were found to be independent predictors of restenosis (longer age: hazard ratio, 0.939; 95% confidence interval, 0.885-0.996; P=.035; longer total SL: hazard ratio, 1.017; 95% confidence interval, 1.00-1.03; P=.045). Restenosis type was diffuse in only 11% and 89% were successfully treated by repeat percutaneous coronary intervention. During a median follow-up of 2 years (interquartile range, 1-4.3 years), major cardiac events other than those angiographically driven at RFUA occurred in 2 patients.. Angiographic restenosis rate remains acceptable in patients with complex CTO successfully treated by DES despite a long SL.

Topics: Aged; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Percutaneous Coronary Intervention; Retrospective Studies; Sirolimus; Treatment Outcome

Neointimal hyperplasia after percutaneous coronary intervention is a major determinant of in-stent restenosis (ISR). Drug-eluting stents (DES) mitigate neointimal hyperplasia and thereby lead to a lower rate of ISR compared with bare-metal stents (BMS). Recent studies have demonstrated that short-term use of oral sirolimus after BMS leads to a significant reduction in ISR. We therefore sought to do a systematic review of studies to determine the angiographic and clinical benefits of early short-term use of oral sirolimus after BMS of native coronary arteries. We conducted PubMed, Embase, Cochrane database review, and Web of Science search of studies comparing oral sirolimus after BMS to BMS alone or DES. Outcomes analyzed were ISR and target lesion revascularization (TLR) as well as major adverse cardiovascular events. A total of 488 patients from 4 studies were included in the review (2006 to 2010). Three studies, comparing BMS alone versus BMS plus oral sirolimus, demonstrated significant reduction in ISR in the oral sirolimus group. Two of these studies also demonstrated significant reduction in TLR at 6-12 month follow-up. The fourth study comparing BMS plus oral sirolimus versus DES showed a lower but nonsignificant reduction in TLR in addition to significant cost saving in the group treated with oral sirolimus. In conclusion, our systematic review demonstrates that early short-term systemic use of sirolimus after BMS resulted in a significant reduction in ISR and TLR. In addition, ISR rates were comparable to DES with the added benefit of cost saving.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Humans; Immunosuppressive Agents; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Stents

This study sought to investigate whether the everolimus-eluting stent (EES) is superior to the paclitaxel-eluting stent (PES) with respect to long-term individual clinical outcomes.. Individual studies have indicated a clinical advantage of coronary EES compared with PES with respect to restenosis and the composite endpoint of major adverse cardiac events. However, these trials were not powered for superiority in low-frequency event rates and have reported limited data beyond 1-year follow-up.. We conducted a meta-analysis of the final 3-year results from the international SPIRIT (Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) II, III, and IV clinical trials. Individual patient data from 4,989 patients who were prospectively randomized to treatment with EES (n = 3,350) or PES (n = 1,639) were pooled for analysis.. At 3-year follow-up, EES was superior to PES in reducing the following event rates: target lesion failure (8.9% vs. 12.5%, hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.59 to 0.85; p = 0.0002), all-cause mortality (3.2% vs 5.1%, HR: 0.65, 95% CI: 0.49 to 0.86; p = 0.003), myocardial infarction (3.2% vs. 5.1%, HR: 0.64, 95% CI: 0.48 to 0.85; p = 0.002), cardiac death or myocardial infarction (4.4% vs. 6.3%, HR: 0.70, 95% CI: 0.54 to 0.90; p = 0.005), ischemia-driven target lesion revascularization (6.0% vs. 8.2%, HR: 0.72, 95% CI: 0.58 to 0.90; p = 0.004), stent thrombosis (0.7% vs. 1.7%, HR: 0.45, 95% CI: 0.26 to 0.78; p = 0.003), and major adverse cardiac events (9.4% vs. 13.0%, HR: 0.71, 95% CI: 0.60 to 0.85; p = 0.0002). No interaction was present between stent type and the 3-year relative rates of target lesion failure across a broad range of subgroups, with the exception of diabetes and vessel (left anterior descending vs. other).. In this large dataset with 3-year follow-up, coronary implantation of EES compared with PES resulted in reduced rates of all-cause mortality, myocardial infarction, ischemia-driven target lesion revascularization, stent thrombosis, and target lesion failure. Further research is warranted to characterize possible interactions between stent type, diabetes, and vessel.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Proportional Hazards Models; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Whether ZES can further improve angiographic and clinical outcomes compared to SES still remains uncertain.. The aim of this study was to assess the efficacy and safety of zotarolimus-eluting stents (ZES) compared with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary interventions (PCI).. Major electronic information sources were explored for randomized controlled trials comparing ZES with SES among patients undergoing PCI during at least 9 months follow-up. The primary efficacy outcomes were target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE); safety outcomes were stent thrombosis (ST), myocardial infarction (MI), and cardiac death.. Seven comparative studies were identified (a total of 5983 patients). When compared with ZES at 12-month follow-up, SES significantly reduced risk of MACE (relative risk [RR]: 0.74, 95% confidence interval [CI]: 0.61 to 0.89, p=0.002), and TLR (RR:0.39; 95% CI: 0.29 to 0.52; p<0.00001), without significant differences in terms of TVR (RR:0.68, 95% CI: 0.38 to 1.20; p=0.18), ST (RR:0.71; 95% CI: 0.39 to 1.31; p=0.28), cardiac death (RR:0.83; 95% CI: 0.49-1.42, p=0.50) or MI (RR:1.08; 95%CI: 0.80 to 1.45; p=0.62).. At 12-month follow-up, SES are superior to ZES in reducing the incidences of TLR and MACE in patients undergoing PCI, without significant differences in terms of TVR, ST, cardiac death, and MI.

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Sirolimus; Treatment Outcome

Relative efficacy and safety of sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) remains controversial. It is unknown whether there are different effect and safety in coronary bifurcation treatment between SES and PES.. The meta-analysis was performed to compare the clinical outcomes of SES and PES in coronary bifurcation intervention.. Five head-to-head clinical trials of SES versus PES in coronary bifurcation intervention were included. A total of 2,567 patients were involved in the meta-analysis. Mean follow-up period ranged from 6 to 35 months. The primary end points were the need for target lesion revascularization (TLR) and main-branch restenosis. Secondary end points were target vessel revascularization (TVR), cardiac death, major adverse cardiac events (MACE), and stent thrombosis.. Compared with PES, SES significantly reduced the risk of TLR (5.3% vs. 10.6%, odds ratio (OR) 0.52; 95% confidence interval (CI) = 0.38-0.70, P < 0.001), main-branch restenosis (4.59% vs. 12.59%, OR 0.31; 95% CI = 0.18-0.55, P < 0.001) and TVR (7.05% vs. 12.57%, OR 0.58; 95% CI = 0.42-0.81, P = 0.001) in coronary bifurcation intervention. In addition, SES group also had a significantly lower incidence of MACE (8.20% vs. 14.13%, OR 0.58; 95% CI = 0.40-0.84, P = 0.004) than PES group. However, there were no statistical difference with respect to the incidence of cardiac death (1.64% vs. 1.09%, P = 0.19) and stent thrombosis (0.84% vs. 1.08%, P = 0.64) between SES and PES groups.. Compared with PES, SES reduced the incidence of TLR, main-branch restenosis and MACE in coronary bifurcation intervention, while the risk of stent thrombosis was similar between SES and PES groups.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Odds Ratio; Paclitaxel; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents.. For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted.. 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up.. In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift.. The Cardiovascular Research Foundation.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Evidence-Based Medicine; Female; Humans; Incidence; Italy; Male; Paclitaxel; Prognosis; Prosthesis Failure; Radiography; Randomized Controlled Trials as Topic; Risk Assessment; Sirolimus; Stents; Survival Analysis; Thrombosis

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Prognosis; Prosthesis Failure; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Sirolimus; Treatment Outcome

Bare metal stents have a proven safety record, but limited long-term efficacy due to in-stent restenosis. First-generation drug-eluting stents successfully countered the restenosis rate, but were hampered by concerns about their long-term safety. Second generation drug-eluting stents have combined the low restenosis rate of the first generation with improved long-term safety. We review the evolution of drug-eluting stents with a focus on the safety, efficacy, and unique characteristics of everolimus-eluting stents.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Patient Selection; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Treatment Outcome

Exaggerated neointimal hyperplasia is considered as the primary mechanism for increased restenosis in patients with diabetes mellitus (DM) treated with bare-metal stent. However, the vessel response in DM and non-DM treated with different drug-eluting stents (DES) has not been systematically evaluated.. We investigated 3D intravascular ultrasound (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391), or everolimus- (n=173) eluting stents. Volumetric data were standardized by length as volume index (VI). At postprocedure, lumen VI at the stented segment was significantly smaller in DM than in non-DM, whereas vessel VI was similar between the 2 groups. At follow-up, neointimal obstruction and maximum cross-sectional narrowing (neointimal area/stent area) were not significantly different between the 2 groups with no interaction for the DES type. Consequently, lumen VI was smaller in DM than in non-DM at follow-up. In the reference segments, residual plaque burden at postprocedure was significantly greater in DM than in non-DM, although change in lumen VI was similar between the 2 groups. The arterial responses at the reference segments also showed no interaction for the DES type.. DM and non-DM lesions showed similar vessel response in both in-stent and reference segments regardless of the DES type. In the DES era, the follow-up lumen in DM patients seems to be determined primarily by the smaller lumen at postprocedure rather than exaggerated neointima within the stent or plaque proliferation at the reference segments.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Linear Models; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The zotarolimus-eluting stent (ZES) is a new drug-eluting stent that delivers zotarolimus, a synthetic analogue of sirolimus, through a biocompatible phosphorylcholine polymer coating. ZES has shown promising results compared with bare-metal stents, but its safety and efficacy against sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents is yet to be established.. We aimed to summarize current evidence from randomized trials comparing ZES with SES and PES.. We searched the Medline, Embase and CENTRAL databases for randomized studies comparing ZES with SES and PES for percutaneous coronary intervention. Relevant clinical and angiographic outcomes were extracted and combined using random and fixed-effect models for heterogeneous and homogenous outcomes, respectively.. Seven randomized trials met the inclusion criteria: ZES group, n=3787; SES group, n=2606; PES group, n=1966. Compared with SES, ZES was associated with significantly higher odds of clinically driven target vessel revascularization (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.78-3.14) and target lesion revascularization (OR 2.46, 95% CI 1.36-4.46). Compared with SES, ZES had higher in-stent restenosis (OR 6.13, 95% CI 3.96-9.50), late lumen loss 'in-stent' (mean difference [MD] 0.39 mm, 95% CI 0.34-0.44) and late lumen loss 'in-segment' (MD 0.18 mm, 95% CI 0.15-0.21). ZES was associated with higher in-stent late lumen loss than PES (MD 0.18 mm, 95% CI 0.07-0.28). There were no differences in mortality, reinfarction or stent thrombosis with ZES compared with SES and PES.. ZES is not superior to PES and is inferior to SES in terms of angiographic outcomes and clinically driven revascularization.

Topics: Coated Materials, Biocompatible; Confidence Intervals; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Equipment Failure; Follow-Up Studies; Humans; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Phosphorylcholine; Randomized Controlled Trials as Topic; Sirolimus; Thrombosis; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Sirolimus; Stents

To perform a systematic review and meta-analysis of studies reporting outcomes after drug-eluting stent (DES) implantation in chronic total occlusions (CTOs).. A review of publications and online databases in January 2010 retrieved 17 published studies that reported outcomes after DES implantation in CTOs: eight uncontrolled studies, seven nonrandomized comparative studies with bare-metal stents (BMS), one post-hoc analysis of a randomized trial, and one randomized trial. Data were pooled using random-effects meta-analysis models.. All published studies evaluated sirolimus- or paclitaxel-eluting stents. All studies reporting comparative angiographic outcomes revealed less binary angiographic restenosis with DES implantation compared to BMS (odds ratio: 0.15, 95% CI: 0.08, 0.26). Over a mean follow-up period of 18.9±16.5 months, the cumulative incidence of death, myocardial infarction, or stent thrombosis was similar between DES and BMS in all studies. Target lesion revascularization (odds ratio: 0.13, 95% CI: 0.06, 0.26) and target vessel revascularization (odds ratio 0.18, 95% CI: 0.11, 0.31) at 6-12 months were consistently lower among DES-treated patients. Similar patterns of safety and efficacy event rates were also observed in studies reporting>12 month outcomes.. Compared with BMS, treatment of chronic total coronary occlusions with DES is associated with significant reductions in angiographic and clinical restenosis with similar safety. The consistency and magnitude of treatment effect across both individual trials and the pooled analysis establish DES as the preferred therapy for percutaneous revascularization of CTOs.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Paclitaxel; Patient Selection; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

First generation drug-eluting stents have shown differential efficacy in high-risk patient subsets at one year. It is unclear whether these differences endure over the medium- to long-term. We compared the five-year clinical efficacy and safety of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in a population of high-risk patients.. The patient cohorts of the ISAR-DESIRE, ISAR-DIABETES, and ISAR-SMART-3 randomized trials were followed up for five years and data were pooled. The primary efficacy endpoint of the analysis was the need for target lesion revascularization (TLR) during a five-year follow-up period. The primary safety endpoint was the combination of death or myocardial infarction (MI) after five years.. A total of 810 patients (405 patients in the SES group and 405 patients in the PES group) was included. Over five years TLR was reduced by 39% with SES compared with PES stent (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.44-0.85; P = 0.004). No difference was observed according to death or MI rates between the two groups (HR 1.10; 95% CI 0.80-1.50; P = 0.57). Definite stent thrombosis occurred in 0.2% (n = 1) in the SES group and in 1.6% (n = 6) in the PES group (HR 0.16; 95% CI 0.02-1.34; P = 0.12).. In high-risk patient subsets the lower rate of 12-month TLR observed with SES in comparison PES is maintained out to five years. In terms of safety, although there was no difference in the overall incidence of death or MI, there was a trend towards more frequent stent thromboses with PES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Disease-Free Survival; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

the everolimus-eluting stent (EES) is a second-generation drug-eluting stent (DES) which is designed to provide better stent deliverability, deployment, safety, and efficacy. We performed a meta-analysis to evaluate the relative safety and efficacy of the EES compared with the paclitaxel-eluting stent (PES).. the published literature was scanned by formal searches of electronic databases from January 2001 to August 2010. All randomized trials comparing EES versus PES and reporting the clinical outcomes were examined for analysis.. a total of four randomized trials were included, involving 6,788 patients. EES were superior to PES with respect to the major adverse cardiac events (cardiac death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (TLR)) within 1-year follow-up (OR 0.57; P < 0.001). The 1-year rates of MI, ischemia-driven TLR, and definite or probable stent thrombosis (ST) were also lower with EES than with PES (OR 0.57, P < 0.001 for MI; OR 0.48, P < 0.001 for TLR; OR 0.34, P < 0.001 for ST). There was no significant difference between EES and PES with respect to cardiac mortality (OR 0.93; P = 0.81).. the EES is superior to the PES in terms of 1-year safety and efficacy.

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Treatment Outcome; Tubulin Modulators

Evidence supporting the use of drug-eluting stents (DES) in saphenous vein graft (SVG) disease is uncertain. Previous studies have suggested that DES might reduce the re-intervention rate in SVG disease, with conflicting data on mortality. Thus, a meta-analysis was performed to compare outcomes of DES vs. bare metal stent (BMS) in SVG disease.. Medline and Web databases were searched for studies comparing DES and BMS for SVG disease, reporting rates of overall mortality, target vessel revascularization (TVR) and myocardial infarction (MI) with a follow-up of ≥6 months. The meta-analysis included 23 studies (7,090 patients). Compared with BMS, DES-treated patients had lower rates of TVR (odds ratio (OR), 0.53; confidence interval (CI), 0.39-0.72; P<0.0001) and overall mortality (OR, 0.63; CI, 0.40-0.99; P=0.05), but similar rates of MI (OR, 0.92; CI, 0.64-1.33; P=0.7). Subgroup analysis highlighted differences between non-randomized studies, in which DES improved mortality rates, and randomized trials, in which benefit from DES was not evident. Meta-regression analysis showed that DES were more effective in the presence of older grafts and type 2 diabetes.. The present meta-analysis showed that, in SVG disease, DES significantly reduced TVR, but did not provide clear benefits on mortality and MI, with an opposite direction of results in mortality observed from randomized and observational data.

Topics: Aged; Aged, 80 and over; Angioplasty; Bias; Clinical Trials as Topic; Coronary Artery Bypass; Coronary Disease; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Paclitaxel; Postoperative Complications; Randomized Controlled Trials as Topic; Regression Analysis; Saphenous Vein; Sirolimus; Stents; Treatment Outcome

Percutaneous coronary intervention (PCI) is an important treatment approach in the management of symptomatic coronary artery disease (CAD). A significant development in PCI in the mid 1970s was balloon angioplasty, followed by bare-metal stents a decade later, and now, the widespread use of drug-eluting stents (DES). While PCI has conferred remarkable benefit to millions of CAD patients, restenosis, and late stent thrombosis associated with DES remain problematic, and improvements are keenly sought. This article reviews recent developments in DES.

Topics: Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Polymers; Sirolimus; Thrombosis; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Atherosclerosis; Coronary Restenosis; Drug Hypersensitivity; Drug-Eluting Stents; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Paclitaxel; Shear Strength; Sirolimus

The cellular and molecular processes that control vascular injury responses after percutaneous coronary intervention involve a complex interplay among vascular cells and progenitor cells that control arterial remodeling, neointimal proliferation, and re-endothelialization. Drug-eluting stents (DES) improve the efficacy of percutaneous coronary intervention by modulating vascular inflammation and preventing neointimal proliferation and restenosis. Although positive effects of DES reduce inflammation and restenosis, negative effects delay re-endothelialization and impair endothelial function. Delayed re-endothelialization and impaired endothelial function are linked to stent thrombosis and adverse clinical outcomes after DES use. Compared with bare-metal stents, DES also differentially modulate mobilization, homing, and differentiation of vascular progenitor cells involved in re-endothelialization and neointimal proliferation. The effects of DES on vascular inflammation and repair directly impact clinical outcomes with these devices and dictate requirements for extended-duration dual antiplatelet therapy.

Topics: Angioplasty, Balloon, Coronary; Antigens, CD34; Cardiovascular Diseases; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Endothelium, Vascular; Humans; Inflammation; Leukocytes; Risk Factors; Sirolimus

Although originally the practice of using balloon catheters proved successful in the short term, the long-term prognosis was less promising because of restenosis, which occurred in >or=30% of patients. This prompted the development of new techniques and mechanical adjuncts, or stents, to maintain lumen patency after balloon angioplasty. Bare metal stents (BMS), the first type of stent used in percutaneous coronary intervention, were designed to address the issues met by balloon angioplasty. BMS reduced the angiographic and clinical restenosis rates in de novo lesions compared to percutaneous transluminal coronary angioplasty alone and decreased the need for emergency coronary artery bypass graft surgery. BMS substantially reduced the incidence of abrupt artery closure, but restenosis still occurred after 6 months in about 20% of cases, necessitating repeat procedures. Drug-eluting stents (DES) improved on the principle of BMS by also delivering drugs locally to inhibit neointimal hyperplasia. DES greatly reduced the incidence of restenosis and resulted in a better safety profile as compared to radiation or systemic drug administration. These advantages and a lower cost compared to surgical interventions make DES an attractive option to treat coronary artery disease. Currently, five DES are available in the USA: the CYPHER sirolimus-eluting stent from Cordis (approved by FDA on 24 April 2003), the TAXUS Express(2) and Liberté paclitaxel-eluting stents from Boston Scientific (approved by FDA on 4 March 2004 and 10 October 2008, respectively) (hereafter TAXUS Express is referred to as TAXUS), the ENDEAVOR zotarolimus-eluting stent from Medtronic (approved by FDA on 1 February 2008), and the XIENCE V everolimus-eluting stent from Abbott Vascular (approved by FDA on 2 July 2008). Following the approval of CYPHER and TAXUS, the clinical data suggested a potential small increase in the rate of stent thrombosis (ST) in DES compared with BMS after implantation. To determine the differences in ST and other rare events between different stents, some modifications have been made to DES clinical trial design, and postmarket surveillance programs have been included to further evaluate the safety and efficacy of each DES. In this review, we will discuss the key clinical outcomes of DES clinical trials, design and key features of the current coronary stents, and major clinical development programs. Postmarket trials, designed to establish long-term safety around ST and o

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Evidence-Based Medicine; Humans; Metals; Myocardial Infarction; Prosthesis Design; Risk Assessment; Sirolimus; Stents; Thrombosis; Treatment Outcome

Drug-eluting stents (DES) offer an attractive option for the treatment of acute thrombotic lesions during acute ST-elevation myocardial infarction (STEMI) due to their ability to inhibit restenosis. Several randomised trials have demonstrated the efficacy of DES in reducing target vessel revascularisation (TVR) in this setting. However, several registries of real-world patients receiving DES for STEMI have raised long-term safety concerns about DES use in this patient subset. Given the inherent limitations of registry data, this issue is likely to remain unresolved until further data is made available from large-scale ongoing trials with long-term follow-up such as the HORIZONS-AMI trial.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coronary Restenosis; Drug-Eluting Stents; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Meta-Analysis as Topic; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Registries; Sirolimus

To assess the safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the TAXUS paclitaxel-eluting stent (PES) in women at two years.. In this pooled analysis, a cohort of 395 women and 906 men was studied by using patient level and lesion level clinical data from SPIRIT II and SPIRIT III studies. Women enrolled in these two studies had higher demographic and lesion risk characteristics than their male counterparts. In-stent and in-segment late loss (LL) was significantly less in the women in the EES group compared to the women in the PES group (in-stent 0.15+/-0.44 mm vs. 0.45+/-0.51 mm; P<0.01, in-segment 0.09+/-0.46 mm vs. 0.29+/-0.40 mm; P<0.01). In women, EES compared to PES resulted in significant reductions in major adverse cardiac events (MACE) (8.5% vs 16.4%; p=0.02) and in target vessel failure (TVF) (11.2% vs 19.5%; p=0.02) at two years. In men, a significant difference was seen in in-stent LL and in-stent % diameter stenosis (DS) favouring EES (in-stent LL 0.14+/-0.33 mm vs. 0.28+/-0.47 mm; P<0.01, in-stent %DS 9.28+/-13.86 vs. 13.64+/-18.31; P<0.01). MACE rates at two years were lower in males treated with EES compared to PES (6.7% vs. 10.9%; p=0.03). The interaction between gender and stent type was not found to be significant for MACE at two years.. In this pooled analysis of two randomised trials, at two years, EES compared to PES resulted in reduced angiographic LL, fewer MACE and TVF events in women and reduced angiographic LL and %DS and fewer MACE events in men.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Paclitaxel; Prosthesis Design; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Single-Blind Method; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

Drug-eluting stents (DES) have revolutionized interventional cardiology. The first bare-metal stents successfully prevented abrupt artery closure and reduced the likelihood of clinical restenosis compared with balloon angioplasty. They were, however, limited by the frequent occurrence of restenosis owing to smooth muscle proliferation, and resultant neointimal hyperplasia and target lesion revascularization. By coating stents with drugs that target smooth muscle cell proliferation, it has been possible to considerably attenuate in-stent restenosis. This innovative technology still has shortcomings, however, and novel approaches are needed to improve the safety and efficacy of DES. The main components that determine the performance of a stent are the stent backbone, active drug, polymer and delivery system, and each of these factors need to be examined to optimize DES platforms. Improvements include the use of new coating technologies, bioabsorbable stents, non-drug-based stent coatings, and tailored lesion therapy. Efforts to develop this technology further will greatly enhance the outcome for patients with coronary artery disease.

Topics: Absorbable Implants; Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Biocompatible Materials; Coronary Restenosis; Drug-Eluting Stents; Hormones; Humans; Immunosuppressive Agents; Muscle, Smooth, Vascular; Paclitaxel; Sirolimus

Sirolimus and tacrolimus are potent immunosuppressants that are delivered by drug-eluting stents (DES) for the prevention of in-stent restenosis. Balloon angioplasty with stent implantation has emerged as a successful treatment for coronary stenoses; angioplasty dilates the vessel lumen and the stent prevents elastic recoil of the vessel walls. However, angioplasty and stent placement both produce vascular injuries that potently stimulate the proliferation of smooth muscle cells, resulting in a thickening of the vascular wall. The purpose of DES is to deliver pharmacological agents that counteract neointimal hyperplasia. The sirolimus-eluting-stent reduces the incidence of in-stent restenosis significantly, whereas the tacrolimus-eluting-stent demonstrates no improvement in clinical benefit compared with a bare stent. Although sirolimus and tacrolimus have similar molecular structures, these drugs regulate immune activation via different mechanisms of action. The effects of this class of drugs are mediated by binding to the FK-506-binding proteins (FKBPs), which are highly evolutionarily conserved across species. This review highlights the structure and function of sirolimus, tacrolimus and FKBPs, with particular focus on recent observations that the two drugs target signaling pathways involved in the control of vascular smooth muscle apoptosis and proliferation directly.

Topics: Animals; Cell Proliferation; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Models, Biological; Muscle, Smooth, Vascular; Protein Binding; Signal Transduction; Sirolimus; Tacrolimus; Tacrolimus Binding Proteins

During the last few decades, with the evolution of techniques and materials and the increasing experience of operators, percutaneous coronary interventions (PCI) have become an equally efficient alternative to coronary artery bypass grafts for the treatment of most coronary stenoses. Bare-metal stent implantation represented a major step forward, compared with plain old balloon angioplasty (POBA), by improving the immediate angiographic success. However, the incidence of in-stent restenosis (ISR) remained unacceptably high. Development of the drug-eluting stent (DES) significantly improved the outcome of PCI by dramatically abating the rate of ISR and reducing the incidence of target lesion revascularization. However, ISR has not been eliminated and the persistence of metal vessel scaffolding also raises concern regarding the occurrence of late or very late stent thrombosis. POBA and stent implantation have been shown to induce a local and systemic inflammatory response, whose magnitude is associated with worse clinical outcome, and they increase the risk of ISR. C-reactive protein, a marker of systemic inflammation, has been demonstrated to predict clinical and angiographic outcome after POBA or bare-metal stent implantation. However, conflicting data regarding the prognostic value of C-reactive protein following DES implantation are available. In this paper, we review the literature regarding the clinical and pathophysiological association between inflammation and prognosis after DES implantation and suggest some possible therapeutic approaches to reduce inflammatory burden with the aim to improve clinical and angiographic outcome after PCI.

Topics: Angioplasty, Balloon, Coronary; Atherosclerosis; C-Reactive Protein; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Inflammation; Myocardial Infarction; Paclitaxel; Predictive Value of Tests; Prognosis; Sirolimus

This meta-analysis was undertaken to assess the efficacy and safety of drug-eluting stents (DESs) compared to bare metal stents (BMSs) in saphenous vein graft (SVG) interventions. DESs decrease the risk of target vessel revascularization in native coronary arteries compared to BMSs. The ideal treatment strategy in patients with SVG disease is unknown. A search of the published reports was conducted to identify studies that compared DESs and BMSs in SVG intervention with a minimum follow-up of 6 months. A total of 19 studies (2 randomized trials and 17 registries), including 3,420 patients who had undergone SVG intervention (DESs, n = 1,489 and BMS, n = 1,931), met the selection criteria. The mean length of follow-up was 20 + or - 12 months. Using the fixed effect model, target vessel revascularization was less frequently performed in patients who had undergone SVG intervention with a DES than with a BMS (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49 to 0.72). The incidence of myocardial infarction was lower in patients with a DES than in those with a BMS (OR 0.69, 95% CI 0.49 to 0.99). No differences were found in the risk of death (OR 0.78, 95% CI 0.59 to 1.02) or stent thrombosis (OR 0.41, 95% CI 0.15 to 1.11) between the 2 groups. In conclusion, these findings support the use of DESs in SVG lesions.

Topics: Antineoplastic Agents, Phytogenic; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Incidence; Myocardial Infarction; Myocardial Revascularization; Paclitaxel; Saphenous Vein; Sirolimus; Treatment Outcome; United States

To compare the efficacy of rapamycin-eluting stents (RES) and paclitaxel-eluting stents (PES) in patients undergo percutaneous coronary intervention.. RES and PES differ significantly with respect to polymer coating and antiproliferative drugs. It is not yet clear whether there are any differences between RES and PES with regard to clinical outcomes.. Systematic searches were conducted of randomized, controlled trials (RCTs) comparing RES with PES in Medline and the Cochrane Database of systematic reviews. A meta-analysis was done of all available randomized studies comparing PES with RES. Information on study design, inclusion and exclusion criteria, number of patients and clinical outcomes was extracted by two investigators. Disagreements were resolved by consensus. The primary outcome was reintervention, target lesion revascularization (TLR) and target vessel revascularization (TVR). Stent restenosis, myocardial infarction (MI) and all-cause mortality were secondary endpoints.. Twenty-one RCTs of RES versus PES with a total number of 10,147 patients were included in this meta-analysis. Indication for angioplasty was either acute coronary syndrome or stable angina. The mean follow-up period ranged from 6 to 24 months. The rates of TLR were 4.9% vs. 7.0%; p = 0.0009 and the rates of TVR were 5.1 vs. 8.3%; p < 0.001 for RES vs. PES, respectively. The incidence of stent restenosis was 3.9% for RES vs. 5.3% for PES; p = 0.004. Rates of MI and all-cause mortality were comparable.. This meta-analysis demonstrates that, as compared to PES, RES seems to be associated with a lower risk of reintervention and stent restenosis. The risk of MI and all-cause death was similar between the two stents.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Treatment Outcome

It has been reported that sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have been more effective than bare-metal stents in reducing restenosis and cardiac events in a broad range of patients with coronary artery disease. However, it is unknown whether there might be differences between these two drug-eluting stents in terms of efficacy and safety in the setting of acute ST-segment elevation myocardial infarction (STEMI).. The aim of the present study was to compare SES with PES in patients with acute STEMI undergoing primary percutaneous coronary intervention (PCI).. The published research was scanned by formal searches of electronic databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials) from January 2001 to February 2010. Internet-based sources of information on the results of clinical trials in cardiology were also searched.. A total of 4 randomized trials were included in the present meta-analysis, involving 1105 patients (550 in the SES group, 555 in the PES group). SES were significantly more effective in the reduction of angiographic binary (≥50%) restenosis (4.0% vs 9.6%, odds ratio 0.38, 95% confidence interval 0.19 to 0.74, P = 0.004) compared to PES. The differences between SES and PES were not statistically significant with respect to target vessel revascularization (TVR), stent thrombosis, cardiac death, and myocardial infarction.. SES are superior to PES in reducing the incidence of restenosis in patients undergoing primary PCI for STEMI, with nonsignificant differences in terms of TVR, cardiac death, myocardial infarction, and stent thrombosis.

Topics: Angioplasty, Balloon, Coronary; Confidence Intervals; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Incidence; Myocardial Infarction; Odds Ratio; Paclitaxel; Sirolimus; Statistics as Topic

The introduction of drug-eluting stents has led to a marked reduction of restenosis, which is a major limitation of percutaneous coronary intervention for coronary artery disease. The next-generation Xience V® (Abbott Vascular, CA, USA) everolimus-eluting stent was designed to address the limitations of first-generation drug-eluting stents. The cobalt-chromium stent platform with an open-cell design offers excellent deliverability. Moreover, the combination of a thin fluoropolymer eluting the antirestenotic drug everolimus provides both an effective suppression of neointimal tissue and rapid re-endothelialization above and between stent struts in preclinical studies. Large randomized clinical trials comparing the everolimus-eluting stent with the Taxus Express® and Liberté® (Boston Scientific, MA, USA) paclitaxel-eluting stents have shown reduced rates of repeat revascularization, myocardial infarction and stent thrombosis at 1-year follow-up with the everolimus-eluting stent. However, we will have to await long-term (5-year) data from these randomized clinical trials with the everolimus-eluting stent to determine whether the observed benefit is robust. Furthermore, data are currently limited the clinical performance of the everolimus-eluting stent relative to drug-eluting stents other than the Taxus Express and Liberté paclitaxel-eluting stents, although a large number of trials are now being conducted to address these questions. In this article, we provide a comprehensive overview of (pre)clinical studies with the everolimus-eluting stent.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Sirolimus; Thrombosis

Restenosis following interventions in the coronary or peripheral arteries develops over weeks to months. In coronary arteries the restenosis rate has been markedly reduced since the advent of drug-eluting stents. Non-stent-based methods for local drug delivery enable restenosis inhibition without the need for stent implantation, does not permanently change the structure of the vessel, are repeatable, and seems to be applicable where drug-eluting stents provide insufficient protection. Preclinical data indicate that short exposure of the vessel wall to a lipophilic inhibitor of cell proliferation is sufficient for preventing restenosis. Initial evidence to this effect emerged from an investigation of paclitaxel embedded in a matrix that enhances the solubility and release of the agent from the balloon coating as well as its transfer to the vessel wall. Further corroborating data from preclinical and clinical studies demonstrating a reduction in late lumen loss and lower restenosis rates led to the market introduction of a variety of paclitaxel-coated angioplasty balloons. The effectiveness of restenosis inhibition is not determined by the active agent alone. Other factors that are crucial for the effectiveness and safety of drug-coated angioplasty balloons are the formulation containing the agent and the coating technique. In this review we first outline the development of paclitaxel-coated balloons to then provide an overview of the preclinical results obtained with different paclitaxel-coated balloons and finally compare these with the outcome in patients. The article concludes with a short outlook on initial results with a zotarolimus-coated angioplasty balloon.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus

Introduction of drug eluting stents (DES) during percutaneous coronary interventions significantly reduces the rate of angiographic restenosis, target lesion and vessel revascularization. In spite of these benefits, other clinical hard end points such as death or myocardial infarction were not reduced and, furthermore, new concerns associated with the presence of late and very late stent thrombosis have been raised. The requirement of long-term dual antiplatelet therapy is another limitation associated with DES. Conversely, in this decade, other options to DES have been simultaneously discussed in observational and randomized studies. Several registries and randomized trials using the systemic approach with anti-inflammatory, immunosuppressive or antiplatelet therapies have been identified and discussed in this manuscript. In spite of all randomized studies with oral therapies in the bare metal stent (BMS) era demonstrating positive reductions in coronary restenosis, this practice has not been introduced clinically. Furthermore, a recent randomized trial comparing oral sirolimus plus BMS versus DES demonstrated that the first approach was cost saving and of comparable efficacy to DES. Conclusive evidence of high incidence of late and very late stent thrombosis with DES, together with clinical limitations for its widespread use, has opened up a large opportunity to search for alternative therapies in coronary restenosis prevention.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Electrocardiography; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Meta-Analysis as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Prosthesis Design; Registries; Sirolimus; Stents; Treatment Outcome; Tubulin Modulators

The purpose of this study was to compare estimates for revascularization and major adverse cardiac events (MACE) (death, myocardial infarction, repeat revascularization) in diabetic patients treated with paclitaxel- and sirolimus-eluting stents (PES and SES).. Outcomes in diabetic patients treated with PES and SES have not been adequately evaluated.. We searched MEDLINE/EMBASE from January 2002 to February 2007 and identified abstracts/presentations from this period at major cardiology conferences. Randomized controlled trials (RCTs) and registries were included if data for diabetic patients treated with PES or SES were available. Point estimates with 95% confidence intervals (CIs) were computed as summary statistics.. In RCTs (13 trials; n = 2,422) similar point estimates for target lesion revascularization (TLR) (PES: 8.6%, 95% CI 6.5% to 11.3%; SES: 7.6%, 95% CI 5.8% to 9.9%) and MACE (PES: 15.4%, 95% CI 12.4% to 19.1%; SES: 12.9%, 95% CI 8.5% to 19.2%) were observed. In head-to-head trials (4 RCTs), no difference in the likelihood of TLR (PES vs. SES) was observed (odds ratio [OR] 1.37, 95% CI 0.64 to 2.9, p = 0.42). In registries (16 registries; n = 10,156), point estimates for target vessel revascularization (TVR) (PES: 5.8%, 95% CI 3.9% to 8.5%; SES: 7.2%, 95% CI 4.6% to 11.2%) and MACE (PES: 10.1%, 95% CI 7.3% to 13.8%; SES: 11.9%, 95% CI 8.6% to 16.4%) were also similar. In registries reporting outcomes with both stents (8 registries for TVR and 7 registries for MACE), the likelihood of TVR (PES vs. SES) (OR 0.77, 95% CI 0.54 to 1.10, p = 0.15) and MACE (OR 0.83, 95% CI 0.68 to 1.01, p = 0.056) were nonsignificantly lower with PES.. This analysis of over 11,000 diabetic patients treated with drug-eluting stents demonstrates single-digit revascularization rates. Furthermore, revascularization and MACE estimates are similar with both PES and SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Odds Ratio; Paclitaxel; Randomized Controlled Trials as Topic; Registries; Risk Assessment; Risk Factors; Sirolimus; Treatment Outcome

Percutaneous coronary revascularization has been a mainstay in the management of coronary artery disease since its introduction in the late 1970s. Bare-metal stents and, more recently, first-generation drug-eluting stents (DES), such as sirolimus-eluting (Cypher) and paclitaxel-eluting stents (Taxus), have further improved results of percutaneous coronary intervention (PCI) by improving early results and reducing the risk of restenosis. There is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis, especially after discontinuation of dual antiplatelet therapy. There are well known caveats on the performance of their respective metallic stent platforms, delivery, and dilation systems, and polymer coatings. Second-generation DES, such as zotarolimus-eluting (Endeavor) and everolimus-eluting stents (Xience V), have recently become available in the USA and/or Europe. The Xience V stent holds the promise of superior anti-restenotic efficacy as well as long-term safety. In addition, this stent is based on the Multi-link platform and delivery system. Recently available data already suggest the superiority of the Xience V stent in comparison to the Taxus stent in terms of prevention of restenosis, without significant untoward events. Nonetheless, the number of patients studied and the follow-up duration are still too limited to enable definitive conclusions. Only indirect meta-analyses can be used to date to compare the Xience V with the Cypher. This systematic review tries to provide a concise and critical appraisal of the data in support of the Xience V everolimus-eluting stent.

Topics: Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Sirolimus

To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus.. Collaborative network meta-analysis.. Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data.. Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point.. 35 trials in 3852 people with diabetes and 10,947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes.. In trials that specified a duration of dual antiplatelet therapy of six months or more after stent implantation, drug eluting stents seemed safe and effective in people both with and without diabetes.

Topics: Blood Vessel Prosthesis; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Paclitaxel; Platelet Aggregation Inhibitors; Prosthesis Failure; Randomized Controlled Trials as Topic; Sirolimus; Stents

Treatment of patients with in-stent restenosis (ISR) remains a challenge. We sought to compare results of sirolimus-eluting stents (SES) with those of bare-metal stents (BMS) in patients with ISR.. The results obtained in the stent arm of two randomized studies were analyzed. The RIBS I study (450 patients with ISR) allocated 224 patients to BMS; the RIBS II study (150 patients with ISR) allocated 76 patients to SES. Complete 1-year follow-up was obtained in all 300 patients treated with stents.. Although inclusion/exclusion criteria were identical in the two studies, when compared with patients in the BMS group, patients in the SES arm had more adverse baseline characteristics, more diffuse lesions, and smaller vessels. However, late angiographic findings including in-segment recurrent restenosis rate (11 vs. 38%, P < 0.001), minimal lumen diameter (2.52 vs. 1.63 mm, P < 0.001), and late loss (0.13 vs. 1.04 mm, P < 0.001) were significantly better after SES. The 1-year event-free survival was also significantly improved in the SES group (88 vs. 78%, P < 0.05), as the result of a lower requirement for repeated revascularizations (10.5 vs. 19.6%, P < 0.05). Prespecified subgroup analyses were consistent with the main outcome measures. After adjusting for (a) imbalances in baseline characteristics (restenosis OR 0.11 [95% confidence interval (CI) 0.03-0.36]; adverse events hazard ratios (HR) 0.33 [95% CI 0.13-0.84]) and (b) the propensity score (restenosis OR 0.08 [95% CI 0.03-0.28]; adverse events HR 0.24 [95% CI 0.09-0.66]), results of the SES group were superior to those obtained in the BMS group.. When compared with BMS, SES improved the long-term clinical and angiographic outcome of patients with ISR.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Metals; Middle Aged; Odds Ratio; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Assessment; Sirolimus; Stents; Time Factors; Treatment Outcome

In recent years, percutaneous coronary intervention (PCI) with drug eluting stents (DES) to treat de novo coronary lesions has been associated with a significant reduction of neointimal hyperplasia and in-stent restenosis. However, several publications raise concerns about long-term safety of DES, especially with the emerging anxiety with the problem of late stent thrombosis. Different registries with DES reported a growing incidence of stent thrombosis up to three years after stent implantation. In parallel with DES introduction in clinical practice in the last seven years, we identified six reported observational and randomized clinical experiences assessing the potential role of oral Sirolimus therapy in the prevention of coronary restenosis after bare metal stent implantation. Three observational and three randomized studies were performed during these years. Several implications were drawn: First, systemic therapy was given for only 14 days after PCI; minor transient side effects were observed in 25% of patients and were completely relieved after discontinuation of the drug. Secondly, angiographic restenosis and late loss are strongly related with Sirolimus blood concentration during the first week of treatment and were significantly reduced compared to non therapy. Finally, in the last randomized study, oral Sirolimus plus bare metal stent were cost saving compared to drug eluting stents with a trend to better clinical late outcome with the oral immunosuppressive therapy. The manuscript also reviews recent patents with new drugs, combination of drugs and DES designs which would improve safety and efficacy in the restenosis prevention after angioplasty.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Coronary Restenosis; Cost-Benefit Analysis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Metals; Randomized Controlled Trials as Topic; Sirolimus

The impact of incomplete stent apposition (ISA) after drug-eluting stent implantation determined by intravascular ultrasound (IVUS) on late clinical events is not well defined.. To evaluate the clinical impact of ISA after sirolimus-eluting stent (SES) placement during a follow-up period of 4 years.. Pooled analysis from the RAVEL, E-SIRIUS and SIRIUS trials, three randomised, multicentre studies comparing SES and bare-metal stents (BMS).. IVUS at angiographic follow-up was available in 325 patients (SES: n = 180, BMS: n = 145). IVUS images were reviewed for the presence of ISA defined as one or more unapposed stent struts. Clinical follow-up was available for a 4-year period in all patients. Frequency, predictors and clinical sequel of ISA at follow-up after SES and BMS implantation were determined.. ISA at follow-up was more common after SES (n = 45 (25%)) than after BMS (n = 12 (8.3%), p<0.001). Canadian Cardiology Society class III or IV angina at stent implantation (odds ratio (OR) = 4.69, 95% CI 2.15 to 10.23, p<0.001) and absence of diabetes (OR = 3.42, 95% CI 1.05 to 11.1, p = 0.041) were predictors of ISA at follow-up after SES placement. Rate of myocardial infarction tended to be slightly higher for ISA than for non-ISA patients. When SES patients only were considered, major adverse cardiac event free survival at 4 years was identical for those with and without ISA at follow-up (11.1% vs 16.3%, p = 0.48).. ISA at follow-up is more common after SES implantation than after BMS implantation. Considering the current very sensitive IVUS definition, ISA appears to be an IVUS finding without significant impact on the incidence of major adverse cardiac events even during long-term follow-up.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sirolimus; Time Factors; Tubulin Modulators; Ultrasonography, Interventional

Topics: Angioplasty, Balloon, Coronary; C-Reactive Protein; Coronary Restenosis; Drug-Eluting Stents; Humans; Inflammation; Interferon-gamma; Interleukin-6; Muscle, Smooth, Vascular; Sirolimus; Tumor Necrosis Factor-alpha; Tunica Intima

Implantation of drug-eluting stents has emerged as the predominant percutaneous revascularization strategy in diabetic patients, despite limited outcomes data. Accordingly, our aim was to conduct a meta-analysis to assess the benefit and safety profile of drug-eluting stents in diabetic patients.. We included randomized trials comparing either the paclitaxel- or sirolimus-eluting stent with a bare-metal stent or with each other in diabetic patients during a follow-up of at least 6 months.. A total of 16 studies were identified, which included 2951 diabetic patients who were followed up for 6 to 12 months. Target lesion revascularization was less frequently performed in patients who received drug-eluting stents compared with bare-metal stents (risk ratio [RR] 0.35, 95% CI 0.27-0.46, P < .0001). Similar reductions were noted in the incidence of major adverse cardiovascular events (RR 0.42, 95% CI 0.31-0.56, P < .0001), in-segment restenosis (RR 0.31, 95% CI 0.25-0.40, P < .0001), and non-Q-wave myocardial infarction (RR 0.57, 95% CI 0.32-0.99, P = .046). Event rates were similar for Q-wave myocardial infarction (RR 0.72, 95% CI 0.25-2.07, P = .54), death (RR 0.64, 95% CI 0.32-1.28, P = .20), and stent thrombosis (RR 0.41, 95% CI 0.13-1.27, P = .12).. In conclusion, diabetic patients who receive drug-eluting stents have a significantly lower incidence of target lesion revascularization, in-segment restenosis and myocardial infarction at 6 to 12 months, compared with bare-metal stents. The rates of mortality and stent thrombosis are similar.

Topics: Aged; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents

Drug-eluting stents (DESs) effectively reduce angiographic restenosis and the clinical need for repeat revascularization procedures as compared with bare-metal stents. Widely publicized concerns arose recently about the incidence of late and very late stent thrombosis with the use of first-generation DESs. Recent systematic reviews and large-scale registry studies demonstrated similar rates of overall mortality and myocardial infarction for patients treated with either DESs or bare-metal stents during long-term follow-up. Careful selection of stent type according to patient and lesion characteristics as well as monitoring of adherence to dual antiplatelet therapy could maximize the therapeutic potential of these devices. The purpose of the present Review is to provide the reader with an overview of the benefits and risks of first-generation DESs that could help physicians select the most appropriate stent type for each patient.

Topics: Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Incidence; Paclitaxel; Platelet Aggregation Inhibitors; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Despite the success of drug-eluting stents (DES) in reducing restenosis and the need for target vessel revascularization, several deficiencies have been unraveled since their first clinical application including the risk of stent thrombosis, undesired effects due to the stent polymer as well as the stent itself, and incomplete inhibition of restenosis (especially in complex lesions). Several novel stent systems are being investigated in order to address these issues. In second-generation DES, the rapamycin analogues zotarolimus and everolimus (and more recently biolimus) have been most extensively studied. Furthermore, special stent-coatings to actively promote endothelial healing (in order to reduce the risk of stent thrombosis) and to further reduce restenosis have been employed. To avoid undesirable effects of currently applied (durable) polymers, biocompatible and bioabsorbable polymers as well as DES delivery systems without the need for a polymer have been developed. Bioabsorbable stents, both polymeric and metallic, were developed to decrease potential late complications after stent implantation. Although most of these innovative novel principles intuitively seem appealing and demonstrate good results in initial clinical evaluations, long-term large-scale studies are necessary in order to reliably assess whether these novel systems are truly superior to first-generation DES with respect to safety and efficacy.

Topics: Coated Materials, Biocompatible; Coronary Restenosis; Coronary Vessels; Drug Delivery Systems; Drug-Eluting Stents; Everolimus; Humans; Polymers; Sirolimus; Thrombosis

Topics: Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Coronary Disease; Coronary Restenosis; Drug Therapy, Combination; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Treatment Outcome

Drug-eluting stents (DES) with antiproliferative drugs attached via polymers on the stent surface have reduced in-stent restenosis and repeat revascularization compared with bare metal stent (BMS) across nearly all lesion and patient subsets. However, the small number of patients with in-stent restenosis after DES treatment still exists. Furthermore, concerns about long-term safety of DES are raised, particularly regarding the higher-than-expected late-event thrombosis. There is no doubt that the DES will continue to play a pivotal role in the treatment of coronary artery disease, yet future designs need to incorporate features that reduce thrombosis and promote endothelialization along with maintaining the efficacy. This review focuses on novel generation of DES, discussing new programs, including new antiproliferative agents, novel polymeric and non polymeric stents.

Topics: Absorbable Implants; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Equipment Design; Everolimus; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Polymers; Prosthesis Design; Sirolimus; Tacrolimus

In-stent thrombosis remains to bo an uncommon but dreadful complication of coronary angioplasty manifesting as sudden death or acute coronary syndrome. Drug-eluting stents (DES) proved to be an effective approach in the prevention and treatment of restenosis across a broad spectrum of lesion and patient subsets. Considerable concerns over this technology were raised when a modest increase in the incidence of very late in-stent thrombosis was demonstrated in DES-treated patients which in some trials even translated into higher mortality and myocardial infarctions compared with bare metal stenting (BMS). Unfortunately, DES not only suppress neointimal formation, but also impair the vessel healing process. Delayed and incomplete endothelialization is frequently observed after DES application. Increased blood thrombogenicity due to the prothrombotic effects of eluting drugs and inadequate platelet inhibition along with altered blood flow through remodeled arteries with dysfunctional endothelium contribute to late DES thrombosis. However, a large amount of data from randomized trials suggest that DES when used on label are not associated with unfavourable clinical outcomes. In these patients DES are probably responsible for a slightly elevated risk of late thrombotic events and simultaneously decreased rates of restenosis-related myocardial infarctions and deaths compared with BMS. The potential benefits and risks of DES off-label stenting are yet to be assessed. Since insufficient platelet inhibition was reported as the strongest predictor of DES thrombosis, the necessity of prolonged dual antiplatelet therapy has constituted a major limitation of this device. Therefore, DES implantation should be particularly avoided in non-compliant patients, in those who are scheduled for major surgery requiring premature discontinuation of dual antiplatelet therapy, and in persons who are at high risk of bleeding. Elective operations in DES patients are suggested to be postponed until 12 months after stenting, while dental procedures, when needed, may be performed on dual antiplatelet treatment. Although recent European and American guidelines recommend dual antiplatelet therapy after DES placement for 6-12 and 12 months, respectively, its optimal duration is a matter of ongoing debate. Subsequent generations of DES developed for a better safety profile as well as novel technologies dedicated to facilitate endothelialization are currently under investigation. Finally, cau

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Endothelium, Vascular; Humans; Immunosuppressive Agents; Platelet Aggregation Inhibitors; Sirolimus

In-stent restenosis (ISR) caused by neointimal hyperplasia is the major drawback after percutaneous coronary intervention (PCI) for obstructive coronary disease, occurring in up to 40% of lesions. Recently, one of the most intriguing new therapies developed is drug-eluting stents (DES) that target the central phenomenon of cellular proliferation that causes ISR. The benefits of stent-based drug delivery include maximizing the local tissue levels of therapeutic agents while minimizing systemic toxicity. Numerous DES using different thin-film polymeric drug carrier have been developed and tested, those eluting either antimitotic or antimicrotublar agents such as sirolimus and paclitaxel have been shown effective in clinical trials. Two DES, the J&J Cypher (sirolimus-eluting) and the Boston Scientific Taxus (paclitaxel-eluting) stents, are commercially available in the U.S. after a number of randomized trials demonstrated reductions in late lumen loss, binary restenosis rate, and need for repeat revascularization compared with bare-metal stents (BMS). Because ISR is multifactorial, ideal agents for DES should inhibit thrombus formation, inflammation and cellular proliferation as well as enhance re-endothelialization. The next generation of DES currently undergoing preclinical studies includes new technology, new stent designs and materials, biological polymers, bioabsorbable stents coated with new drugs including stent based gene, as well as cell delivery. The current paper will review and discuss the current and future status of DES.

Topics: Animals; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Humans; Molecular Structure; Paclitaxel; Prosthesis Design; Sirolimus; Stents

Drug-eluting stents (DES) have been shown to be safe and significantly reduce clinical events and angiographic restenosis in the percutaneous treatment of coronary artery disease. Currently, three DES have been approved in Europe and Northern America: the sirolimus-eluting stent (SES), the paclitaxel-eluting stent (PES) and the zotarolimus-eluting stent (ZES). Everolimus, an analog of sirolimus, is an immunosuppressive and antiproliferative agent. In three studies, the SPIRIT I, FUTURE I and II, the everolimus-eluting stent has proven to be safe, well-tolerated and has shown very favorable clinical and angiographic results. Compared with earlier-generation DES, the XIENCE V everolimus-eluting coronary stent system (Advanced Cardiovascular Systems Inc., an Abbott Vascular Company, CA, USA) may provide enhanced deliverability, radiopacity with thinner strut filaments and, owing to a durable polymer, sustained drug elution and vascular compatibility.

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Everolimus; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents; Technology Assessment, Biomedical

Controversy exists about the clinical significance of in-stent late loss (ISLL) after drug-eluting stent (DES) implantation. We sought to clarify whether ISLL after DES implantation is related to a potential clinical impact.. We included in a meta-regression analysis 21 trials (8641 patients) that randomly compared DES with bare-metal stents (BMS). We evaluated the relationship between angiographic behaviour of DES and the clinical impact of using DES instead of BMS in each trial using meta-regression techniques, weighting by the number of patients included in each trial. Mean ISLL in patients allocated to DES and DeltaISLL (difference in ISLL in patients allocated to BMS and DES) were used as angiographic parameters of efficacy of DES. The number of patients needed to be treated (NNT) to prevent one target lesion revascularization (TLR) was used to quantify the clinical impact of using DES instead of BMS. There was a significant relationship between mean ISLL in patients allocated to DES and the clinical benefit of using DES instead of BMS, as measured with the NNT for TLR: NNT for TLR = 6.2 + 18.4 [ISLL-DES] (R = 0.62; P = 0.007). Therefore, a 0.1 mm increase in mean ISLL-DES was associated with a 1.8 increase in NNT for TLR. There was also a significant association between the degree of inhibition of neointimal hyperplasia of DES in comparison with BMS with the NNT for TLR: NNT for TLR = 17.1-11.8 [DeltaISLL] (R = 0.61; P = 0.008). Therefore, a 0.1 mm reduction in ISLL by using DES instead of BMS was associated with a 1.2 decrease in mean NNT for TLR.. There is a strong and significant association between the degree of inhibition of neointimal formation with the use of DES and the clinical impact of using DES instead of BMS.

Topics: Coronary Restenosis; Delayed-Action Preparations; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Tacrolimus; Tubulin Modulators

Definitions of stent thrombosis that have been used in clinical trials of drug-eluting stents have been restrictive and have not been used in a uniform manner.. We applied a hierarchical classification of stent thrombosis set by the Academic Research Consortium (ARC) across randomized trials involving 878 patients treated with sirolimus-eluting stents, 1400 treated with paclitaxel-eluting stents, and 2267 treated with bare-metal stents. We then pooled 4 years of follow-up data. All events were adjudicated by an independent clinical-events committee.. The cumulative incidence of stent thrombosis according to the original protocol definitions was 1.2% in the sirolimus-stent group versus 0.6% in the bare-metal-stent group (P=0.20; 95% confidence interval [CI], -0.4 to 1.5) and 1.3% in the paclitaxel-stent group versus 0.8% in the bare-metal-stent group (P=0.24; 95% CI, -0.3 to 1.4). The incidence of definite or probable stent thrombosis as defined by the ARC was 1.5% in the sirolimus-stent group versus 1.7% in the bare-metal-stent group (P=0.70; 95% CI, -1.5 to 1.0) and 1.8% in the paclitaxel-stent group versus 1.4% in the bare-metal-stent group (P=0.52; 95% CI, -0.7 to 1.4). The incidence of definite or probable events occurring 1 to 4 years after implantation was 0.9% in the sirolimus-stent group versus 0.4% in the bare-metal-stent group and 0.9% in the paclitaxel-stent group versus 0.6% in the bare-metal-stent group.. The incidence of stent thrombosis did not differ significantly between patients with drug-eluting stents and those with bare-metal stents in randomized clinical trials, although the power to detect small differences in rates was limited.

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Combined Modality Therapy; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Platelet Aggregation Inhibitors; Prosthesis Design; Prosthesis Failure; Randomized Controlled Trials as Topic; Sirolimus; Stents

The long-term effects of treatment with sirolimus-eluting stents, as compared with bare-metal stents, have not been established.. We performed an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents (mean follow-up interval, 12.1 to 58.9 months). The primary end point was death from any cause. Other outcomes were stent thrombosis, the composite end point of death or myocardial infarction, and the composite of death, myocardial infarction, or reintervention.. The overall risk of death (hazard ratio, 1.03; 95% confidence interval [CI], 0.80 to 1.30) and the combined risk of death or myocardial infarction (hazard ratio, 0.97; 95% CI, 0.81 to 1.16) were not significantly different for patients receiving sirolimus-eluting stents versus bare-metal stents. There was a significant reduction in the combined risk of death, myocardial infarction, or reintervention (hazard ratio, 0.43; 95% CI, 0.34 to 0.54) associated with the use of sirolimus-eluting stents. There was no significant difference in the overall risk of stent thrombosis with sirolimus-eluting stents versus bare-metal stents (hazard ratio, 1.09; 95% CI, 0.64 to 1.86). However, there was evidence of a slight increase in the risk of stent thrombosis associated with sirolimus-eluting stents after the first year.. The use of sirolimus-eluting stents does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents. There is a sustained reduction in the need for reintervention after the use of sirolimus-eluting stents. The risk of stent thrombosis is at least as great as that seen with bare-metal stents.

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Drug Delivery Systems; Follow-Up Studies; Humans; Immunosuppressive Agents; Myocardial Infarction; Prosthesis Design; Prosthesis Failure; Randomized Controlled Trials as Topic; Regression Analysis; Risk; Sirolimus; Stents; Survival Analysis

The safety of drug-eluting stents has been called into question by recent reports of increased stent thrombosis, myocardial infarction, and death. Such studies have been inconclusive because of their insufficient size, the use of historical controls, a limited duration of follow-up, and a lack of access to original source data.. We performed a pooled analysis of data from four double-blind trials in which 1748 patients were randomly assigned to receive either sirolimus-eluting stents or bare-metal stents and five double-blind trials in which 3513 patients were randomly assigned to receive either paclitaxel-eluting stents or bare-metal stents; we then analyzed the major clinical end points of the trials.. The 4-year rates of stent thrombosis were 1.2% in the sirolimus-stent group versus 0.6% in the bare-metal-stent group (P=0.20) and 1.3% in the paclitaxel-stent group versus 0.9% in the bare-metal-stent group (P=0.30). However, after 1 year, there were five episodes of stent thrombosis in patients with sirolimus-eluting stents versus none in patients with bare-metal stents (P=0.025) and nine episodes in patients with paclitaxel-eluting stents versus two in patients with bare-metal stents (P=0.028). The 4-year rates of target-lesion revascularization were markedly reduced in both the sirolimus-stent group and the paclitaxel-stent group, as compared with the bare-metal-stent groups. The rates of death or myocardial infarction did not differ significantly between the groups with drug-eluting stents and those with bare-metal stents.. Stent thrombosis after 1 year was more common with both sirolimus-eluting stents and paclitaxel-eluting stents than with bare-metal stents. Both drug-eluting stents were associated with a marked reduction in target-lesion revascularization. There were no significant differences in the cumulative rates of death or myocardial infarction at 4 years.

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prosthesis Design; Prosthesis Failure; Randomized Controlled Trials as Topic; Sirolimus; Stents

Drug-coated stent play an important role in percutaneous transluminal coronary angioplasty (PTCA), and it constitutes an innovation to further reduce the incidence of restenosis. In this paper, the mechanisms and the process of endovascular stent implantation,and the principles of drug release of drug-coated stent are reviewed. Especially, polymer coated design and the further development of drug eluting stents are discussed.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Heparin; Humans; Paclitaxel; Sirolimus

Stent thrombosis has become a major concern for interventional cardiology. Although infrequent, it is associated with significant morbidity and mortality. Recent attention has focused on the frequency of this complication with drug-eluting stents compared with bare-metal stents in regard to the timing (early, late, or very late) of the event, underlying mechanisms involved, and preventive strategies. Although dual antiplatelet therapy (aspirin plus thienopyridine) is crucial in mitigating the problem, there are significant issues with this management strategy, including the duration of dual antiplatelet treatment, patient compliance, variability in individual response to therapy, bleeding risk, and management of subsequent noncardiac surgical procedures. Newer strategies being evaluated to enhance the safety of drug-eluting stents include different alloys and stent designs, revisions in the polymer or drug utilized, and, ultimately, bioabsorbable platforms.

Topics: Agnosia; Antineoplastic Agents, Phytogenic; Blood Vessel Prosthesis Implantation; Coronary Restenosis; Drug-Eluting Stents; Global Health; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Incidence; Metals; Myocardial Ischemia; Paclitaxel; Prosthesis Failure; Sirolimus

Since the first percutaneous transluminal coronary angioplasty performed by A. Gruentzig in 1977, percutaneous coronary interventions have become the most important treatment modality for coronary heart disease. Coronary angioplasty carried a significant risk of coronary flow-limiting dissections and restenosis during the first six months following the procedure. Two main studies comparing percutaneous transluminal coronary angioplasty and coronary stenting (STRESS and BENESTENT) performed in 1994 showed a significant reduction in restenosis rate using stents. Thus, until now stents are the most widely used devices for coronary intervention despite two problems: subacute stent thrombosis (1-2%) and still high restenosis rate (5-40%). Subacute stent thrombosis occurs within the first month after stent placement and can be prevented using the double antiplatelet regimen with aspirin and clopidogrel. Some risk of subacute thrombosis remains beyond the first month when drug-eluting stents are used. This requires prolonged antiplatelet therapy. Drug-eluting stents are the most significant innovation in interventional cardiology. They can reduce the incidence of restenosis in native stable coronary arteries to 3-5%. However, the long-term studies comparing bare-metal stents and drug-eluting stents did not show any significant differences in the rate of major adverse cardiac events (death, myocardial infarction), especially in patients with diabetes after the treatment of bifurcational lesions. According to proposed recommendations, drug-eluting stents should be used in small vessels, restenotic lesions, and in saphenous vein grafts. Despite some disadvantages, the results of coronary stenting using drug-eluting stents continue to improve.

Topics: Aged; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Anti-Inflammatory Agents; Aspirin; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Diabetes Complications; Drug Delivery Systems; Drug Therapy, Combination; Fibrinolytic Agents; Follow-Up Studies; Humans; Immunosuppressive Agents; Middle Aged; Platelet Aggregation Inhibitors; Prednisolone; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Stents; Ticlopidine; Time Factors; Treatment Outcome

Drug-eluting stents (DESs) have decreased the incidence of in-stent restenosis. Within the past 2 years several cases on late stent thrombosis (LST) have been reported. This study analyzed and reviewed all published cases of LST in DESs to explore possible trends not previously reported. We applied a Medline search using the key word "drug eluting stents." All 845 positive matches in March 2006 were screened for case reports of LST in DESs, defined as angiographic stent thrombosis >or=30 days after deployment. We included reported LSTs from randomized trials, observational registry reports, and letters to the editor if information regarding timing from stent deployment to clinical event, vessel, stent diameter and length, and antiplatelet regimen were available. There was no significant difference in the incidence of LST between sirolimus- and paclitaxel-eluting stents. Median time from stent deployment to clinical event was 242 days (total range 39 to 927). If aspirin and clopidogrel were discontinued, median time to clinical event was 7 days (3 to 150). In comparison, if only clopidogrel was discontinued, median time to clinical event was 30 days (14 to 690, p <0.0001). There was no significant difference in stent diameter and length between sirolimus- and paclitaxel-eluting stents. Forty-two percent of events occurred in relation to a surgical procedure for which the 2 antiplatelet agents or clopidogrel alone was discontinued. In conclusion, there was a strong association between occurrence of LST and cessation of dual antiplatelet therapy. Patients who continued on aspirin had a significant delay to the clinical event. Efforts should be made to maintain patients on aspirin during routine surgical procedures.

Topics: Coronary Restenosis; Coronary Thrombosis; Equipment Design; Fibrinolytic Agents; Humans; Paclitaxel; Platelet Aggregation Inhibitors; Sirolimus; Stents; Time Factors

Drug-eluting stents reduce restenosis after percutaneous coronary intervention, but may carry an increased risk of late stent thrombosis compared with bare metal stents. Delayed endothelialization may contribute to this phenomenon, that carries a considerable mortality. The current review discusses recent data regarding the risk of late stent thrombosis with drug-eluting stents. An important risk factor is premature discontinuation of antiplatelet therapy, and patients with drug-eluting stents should adhere to dual antiplatelet therapy for one year after stent implantation.

Topics: Coronary Restenosis; Drug Delivery Systems; Humans; Paclitaxel; Risk Factors; Sirolimus; Stents; Thrombosis; Time Factors

Diabetes mellitus is a major risk factor for restenosis in patients undergoing percutaneous coronary intervention. Randomized controlled trials comparing drug-eluting stents (DESs) with bare metal stents (BMSs) showed a marked decrease in in-stent restenosis and target lesion revascularization with DESs in the total patient population enrolled in the studies, including patients with diabetes. However, it remains unclear whether the antirestenotic benefit of DESs is preserved in the high-risk diabetic subgroup. MEDLINE, EMBASE, ISI Web of Knowledge, Current Contents, International Pharmaceutical Abstracts, and recent Scientific Sessions databases were searched to identify relevant clinical trials comparing DESs with BMSs. A randomized controlled trial was included if it provided outcome data for patients with diabetes for > or =1 of the following: late lumen loss, in-stent restenosis, or target lesion revascularization. Data were combined using fixed-effects models, and standard tests for heterogeneity were performed. Eight studies with 1,520 patients with diabetes were identified that reported > or =1 outcome of interest. Mean late lumen losses (7 studies) were 0.93 mm (95% confidence interval [CI] 0.510 to 1.348) with BMSs and 0.18 mm (95% CI -0.088 to +0.446) with DESs. For patients receiving a DES, this translated into a marked decrease in in-stent restenosis (7 studies, RR 0.14, 95% CI 0.10 to 0.22, p <0.001) and target lesion revascularization (8 studies, RR 0.34, 95% CI 0.26 to 0.45, p <0.001). DES use is associated with a marked decrease in in-stent restenosis and target lesion revascularization in patients with diabetes. In conclusion, the analysis supports the current widespread use of DESs in these high-risk patients.

Topics: Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Databases, Factual; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Paclitaxel; Prosthesis Design; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Drug-eluting stents have radically changed the way we treat coronary artery disease. They offer lower restenotic rates compared with the bare metal stents and this enables more challenging and complex lesions to be treated. However, there are still limitations as restenosis has not been completely abolished and there are concerns about stent thrombosis. The next generation stents offer the technology to address these pertinent issues. This review examines the new analogs of the sirolimus family and their use in novel stent platforms, including the use of biodegradable and bioabsorbable materials employed in both stents and on the polymer. "Reservoir stents" that are specially designed to contain layers of drugs in pockets with different release profiles are discussed and an insight into the emerging field of bioengineered stents is highlighted.

Topics: Biocompatible Materials; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Polymers; Prosthesis Design; Sirolimus; Stents

Polymer-based sirolimus- (Cypher) and paclitaxel-eluting (Taxus) drug eluting stents have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention (PCI). Although these stents reduce rates of restenosis compared with bare metal stents (BMS), late thrombosis, a life threatening complication, has emerged as a major safety concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that both DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared with BMS. This delayed healing is the primary substrate underlying all cases of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis such as penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions represent additional barriers to healing and should be avoided if DES are to be used to minimize the risk of late thrombosis. Because the time course of complete healing with DES in man is unknown, the optimal duration of antiplatelet treatment remains to be determined.

Topics: Aged; Angioplasty, Balloon, Coronary; Animals; Biopsy, Needle; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Disease Models, Animal; Endothelium, Vascular; Humans; Immunohistochemistry; Middle Aged; Paclitaxel; Prognosis; Prosthesis Design; Rabbits; Risk Factors; Sensitivity and Specificity; Sirolimus; Stents; Time Factors; Wound Healing

The sirolimus-eluting coronary stent received CE Mark approval in Europe in April 2002. In the US, FDA approval followed in April 2003. Since the preliminary results from the First-in-Man feasibility study were presented, several randomized, controlled trials have documented the profound antiproliferative effects of sirolimus, a macrolide antibiotic and potent cytostatic inhibitor of smooth muscle cell proliferation. Subsequently, the body of clinical evidence was increased by the second wave of evidence from trials in more complex lesions (such as in-stent restenosis, small vessels, chronic total occlusions) and "high-risk" patients such as those with diabetes. More recently we have had the opportunity to compare the two commercially available drug-eluting stents following the presentation of data from six head-to-head trials. As a result of numerous single and multi-center, national and international studies in which the safety and efficacy of sirolimus-eluting coronary stents have been subjected to close scrutiny, the global interventional cardiology community now has a wealth of evidence in support of the use of this technology resulting in dramatically improved patient outcomes after percutaneous intervention.

Topics: Blood Vessel Prosthesis Implantation; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Restenosis; Humans; Immunosuppressive Agents; Risk Factors; Sirolimus; Stents; Treatment Outcome

This review presents the current data on drug release from drug-eluting stents and the effects of the release profiles on animal and human data for coronary stenosis. Data for the two most important drugs, sirolimus (rapamycin) and paclitaxel, are presented, the polymers used are described and the observed release profiles are discussed for various polymer carriers. The current literature on the tissue compatibility of the polymers commonly used in drug-eluting stents is also discussed. The range of release rates from stents studied to date is limited for sirolimus, but somewhat broader for paclitaxel. Animal and human data comparing the different release profiles are limited to about 6 months for animals and 2-4 years for humans. From the data available, it appears that for both sirolimus and paclitaxel, a slow-releasing drug-eluting stent leads to slightly more favorable angiographic outcomes than more rapid release. Most of the complications arising from the use of drug-eluting stents are attributed to incomplete healing; one possible clinical consequence of this delay in healing is that anti-platelet therapy needs to be maintained over a much longer period than is the case for bare metal stents.

Topics: Animals; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Follow-Up Studies; Humans; Immunosuppressive Agents; Paclitaxel; Prosthesis Design; Randomized Controlled Trials as Topic; Sirolimus; Stents; Time Factors; Uncertainty

The advent of intravascular stenting dramatically reduced the incidence of restenosis among patients undergoing percutaneous transluminal coronary angioplasty. However, a substantial percentage of patients, particularly those with risk factors such as diabetes mellitus or complicated lesions, remain at risk for restenosis. Drug-eluting stents overcome this problem by releasing bioactive agents from a polymeric coating directly into the vessel wall, inhibiting the cellular mechanisms of restenosis while avoiding systemic toxicity. Recent data indicate that local targeting of the proliferative process with drug-eluting stents dramatically reduces the risk for restenosis, even among high-risk patients. A range of bioactive coatings are currently available or in late clinical trials. Both sirolimus- and paclitaxel-eluting stents have demonstrated efficacy in a broad range of patient types; early data from clinical trials of second-generation stent coatings, such as everolimus and ABT-578 (zotarolimus), suggest that these agents are also effective in preventing restenosis. This article reviews the pathophysiology of in-stent restenosis and surveys recent key clinical trials of drug-eluting stents.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Paclitaxel; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Stents; Treatment Outcome; Tubulin Modulators

Recent evidence shows that drug-eluting stent devices (DES) substantially reduce the risk of in-stent restenosis compared with classic bare metal stent devices (BMS). In Belgium, however, the use of BMS is still standard procedure due to the higher prices of the newer DES. Although the use of DES is more expensive in the short term it might be beneficial in the long term due to the avoidance of revascularization costs. The primary objective of this study is to compare the net cost of DES and BMS from the perspective of Belgian health care.. Cost differences between DES and BMS are determined by the difference in stent price and the difference in the rate of re-intervention. The cost of revascularization of patients with in-stent restenosis was estimated based on data gathered at the Antwerp University hospital (UZA). Data on effectiveness were obtained from a literature meta-analysis. Because of some important study limitations, a sensitivity analysis was included in this study. In general, the use of DES was cost saving as compared with BMS, with savings amounting to E 165 for Cypher stent devices and Euro 128 for Taxus stent devices in the base case scenario. For patients with a high risk of restenosis net savings persist in almost all sensitivity analyses.. The use of DES in patients with a high in-stent restenosis risk is cost saving. Price evolutions in the stent device market predict that the use of DES, if not yet cost saving, will become cost saving in the near future for all types of patients. Recent evidence, however, casts some doubt on the long-term effectiveness of DES.

Topics: Angioplasty, Balloon, Coronary; Belgium; Coronary Artery Bypass; Coronary Restenosis; Cost-Benefit Analysis; Drug-Eluting Stents; Follow-Up Studies; Humans; Metals; Paclitaxel; Prosthesis Design; Reoperation; Research Design; Retrospective Studies; Sensitivity and Specificity; Sirolimus; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Coronary Disease; Coronary Restenosis; Drug Implants; Humans; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Saphenous Vein; Sirolimus; Stents; Treatment Outcome

The only routinely available tool for assessing many features of stent implantation, intravascular ultrasound (IVUS) has become indispensable in trials of drug-eluting stents (DESs) and is currently the best way to identify or exclude causes of DES failure. Although IVUS resolution is not sufficient for determining reendothelialization, serial (postprocedure and follow-up) IVUS can measure intimal hyperplasia (IH), assess acute and late incomplete stent apposition, detect the presence and persistence of edge dissections, assess vascular responses such as remodeling, study edge effects, compare overlapping with nonoverlapping segments, and look for causes of restenosis and thrombosis. Percentage IH volume is one IVUS measure of efficacy that has been routinely assessed and compared in studies of DESs; IH volume and external elastic membrane, luminal, and stent cross-sectional area are others. This review details and evaluates IVUS findings in the important clinical trials conducted with the first-generation DESs: a sirolimus-eluting stent, a polymeric paclitaxel-eluting stent, and a nonpolymeric paclitaxel-eluting stent. IVUS results apparent in DES failure (restenosis and thrombosis) are also examined.

Topics: Anti-Bacterial Agents; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Humans; Hyperplasia; Sirolimus; Tunica Intima; Ultrasonography, Interventional

Small vessel size (<3 mm) has been identified as an independent predictive factor of restenosis after percutaneous coronary intervention when using bare metal stents (BMS). It remains controversial whether BMS placement in small vessels has an advantage over balloon angioplasty in terms of angiographic and clinical outcomes. The advent of drug eluting stents (DES), either paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES), has strongly impacted interventional cardiology by significantly reducing restenosis and the need for repeat revascularization. Therefore, it was also expected that DES could substantially reduce restenosis in smaller vessels. However, even in the DES era, small vessel size remains an independent predictor of angiographic and clinical restenosis. To date, only a few studies systematically investigate the clinical effect of DES placement in small vessels. In addition, some potential issues with the use of DES have been raised, such as late stent thrombosis and late restenosis. In order to (i) establish the superiority of DES over BMS; (ii) verify the efficacy and safety of DES; and (iii) critically assess the superiority of one DES over the other in patients with small coronary arteries, further multicenter, randomized clinical trials with larger sample size are warranted.

Topics: Blood Vessels; Coronary Restenosis; Drug-Eluting Stents; Paclitaxel; Sirolimus; Stents

The safety and efficacy of drug-eluting stents reduce the need for surgical revascularization. The objective of the present study was to investigate whether paclitaxel or rapamycin-eluting stent are effective in avoiding the need for coronary-artery bypass grafting.. This was a systematic review of the literature using the methodology of the Cochrane Collaboration. The type of study considered was controlled randomized trials; the type of intervention was drug-eluting or bare-metal stents; and the main outcome investigated was coronary-artery bypass grafting.. The ten studies included in this systematic review did not show any statistically significant difference between the drug-eluting stents and the bare-metal stents with regard to the outcome of coronary-artery bypass grafting (confidence interval: 0.31 to 1.42).. The surgical revascularization rate was not reduced by the use of drug-eluting stents.

Topics: Coronary Artery Bypass; Coronary Restenosis; Cytostatic Agents; Drug-Eluting Stents; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

The author presented a review of clinical research works conducted and completed in 2001 - 2005. The review contains data on clinical trials of sirolimus-eluting stents in patients with coronary artery disease. The author analyzed experimental data on the mechanism of action of rapamycin on the cell and also analyzed data of clinical trials of sirolimus-containing stents in the treatment of coronary artery stenosis and chronic occlusion. Results of clinical trials of coated stents in diabetic patients with coronary artery stenosis, as well as data on the use sirolimus-containing stents in the treatment in stent restenosis were also discussed.

Topics: Anti-Bacterial Agents; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Sirolimus; Treatment Outcome

To confirm the overall benefit of drug eluting stents (DES), to evaluate the effect of different DES, and to assess the global safety of DES compared with bare stents through a meta-analysis of randomised controlled trials.. Randomised controlled trials comparing sirolimus and derivates or paclitaxel and derivates eluting stents versus bare stents. Binary restenosis and major adverse cardiac events (MACE) were chosen as primary end points. Death, Q wave myocardial infarction (MI), and stent thrombosis up to 12 months' follow up were also analysed.. MACE overall occurrence was highly reduced with DES from 19.9% to 10.1% (odds ratio (OR) 0.46, 95% confidence interval (CI) 0.41 to 0.52, p < 0.001). A significant heterogeneity (p < 0.001) was found between subgroups according to the drug: MACE OR was 0.28 (95% CI 0.22 to 0.35) in the sirolimus subgroup and 0.62 (95% CI 0.53 to 0.73) in the paclitaxel subgroup. Restenosis was also highly reduced from 31.7% with bare stents to 10.5% with DES (OR 0.25, 95% CI 0.22 to 0.29, p < 0.001) with a similar heterogeneity between subgroups. Mortality, Q wave MI, and stent thrombosis were not significantly different between DES and control group, whereas Q wave MI and stent thrombosis tended to be more frequent with paclitaxel.. This meta-analysis confirms the overall benefit of DES on restenosis and MACE with significant heterogeneity between drugs, suggesting higher efficacy of sirolimus eluting stents. Additional data with longer follow up and in high risk populations are needed to clarify issues on stent thrombosis.

Topics: Blood Vessel Prosthesis; Coronary Restenosis; Drug Implants; Humans; Immunosuppressive Agents; Paclitaxel; Prosthesis Failure; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

To examine whether polymer based coronary stents eluting sirolimus or paclitaxel are equally effective in patients with and without diabetes.. Systematic review and meta-analysis by indirect comparison of randomised controlled trials comparing stents eluting sirolimus or paclitaxel with conventional bare metal stents. The overall study population and patients with and without diabetes were analysed separately by using the ratio of incidence rate ratios (RIRR).. The analysis was based on 10 trials (six with sirolimus, four with paclitaxel), 4513 patients (1146 patients with diabetes), 5755 years of follow up, and 2464 events. In patients without diabetes sirolimus eluting stents were superior to paclitaxel eluting stents with respect to in-stent (RIRR 0.21, 95% confidence interval (CI) 0.10 to 0.48, p < 0.001) and in-segment restenosis (RIRR 0.47, 95% CI 0.24 to 0.92, p = 0.027), target lesion revascularisation (RIRR 0.54, 95% CI 0.30 to 0.99, p = 0.045), and major adverse cardiac events (RIRR 0.46, 95% CI 0.26 to 0.83, p = 0.010). In patients with diabetes the two drug eluting stents did not differ significantly in any of these end points. Meta-regression analysis showed a significant difference between patients with and without diabetes (tests for interaction for in-stent and in-segment restenosis, p = 0.036 and p = 0.016).. Indirect evidence indicates that sirolimus eluting stents are superior to paclitaxel eluting stents in patients without diabetes but not in patients with diabetes.

Topics: Blood Vessel Prosthesis; Coronary Restenosis; Diabetic Angiopathies; Drug Implants; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents

Sirolimus is one of the intensively investigated drugs with pluripotent activities. It binds to its intracellular receptor FKBP12 (FK506-binding protein 12), a member of the family of FK506-binding proteins, and inhibits the activity of mTOR, a serine/threonine kinase involved in numerous cell processes linked to cell growth control. The drug is currently registered for the prophylaxis of organ rejection and for use in coronary stents. However, unique characteristics of sirolimus make it a good candidate for anti-cancer therapy. Indeed, phase II and III clinical studies in humans with several types of neoplasms are already under way. The review describes molecular activity of sirolimus and its analogs, characteristic for specific applications, in view of very recent advances involving tuberous sclerosis complex (TSC)-mediated signaling pathways. Current studies with sirolimus performed in tuberous sclerosis animal models are presented. Possible application of sirolimus for treating tuberous sclerosis, disease caused by mutations of TSC proteins, is discussed.

Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Coronary Restenosis; Drug Resistance; Graft Rejection; Humans; Immunosuppressive Agents; Protein Kinases; Sirolimus; Tacrolimus Binding Protein 1A; TOR Serine-Threonine Kinases; Tuberous Sclerosis; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins; Vascular Endothelial Growth Factor A

Despite the success of coronary stent implantations in the last decade, in-stent restenosis due to neointimal hyperplasia remains a problem to overcome. Neointimal hyperplasia is a vascular response to stent injury and mainly consists of proliferation of smooth muscle cells and deposition of extracellular matrix. Recently, local drug delivery has been advocated as a potential strategy to prevent in-stent restenosis. Unprecedented results have been obtained in early clinical studies on sirolimus-eluting and paclitaxel-eluting stents. Trials using various pharmaceutical coatings on different coronary stents are ongoing. More types of drug-eluting stents are expected on the market in the near future. Meanwhile, the evaluation of drug-eluting stents is entering the second phase in which the safety and efficacy in more complex lesion subsets and different clinical presentations are being investigated. Results including cost-benefit analyses are expected to have a tremendous impact on the practice of interventional cardiology in the next decade.

Topics: Animals; Anti-Bacterial Agents; Coronary Restenosis; Disease Models, Animal; Drug Delivery Systems; Drug-Eluting Stents; Humans; Paclitaxel; Prosthesis Design; Sirolimus; Tubulin Modulators

Recent clinical studies that investigated the efficacy of the two U.S. Food and Drug Administration-approved drug-eluting stent (DES) platforms Cypher (Cordis, Johnson and Johnson, Miami Lakes, Florida) and Taxus (Boston Scientific, Boston, Massachusetts) suggest that there are differences between both DES concerning neointimal growth. Both DES elute compounds that inhibit the cell cycle, but at different stages: Cypher stents elute sirolimus, which induces G1 cell cycle inhibition, and Taxus stents release paclitaxel, which predominantly leads to M-phase arrest. In an attempt to explain the differences observed in human studies, the properties of these stent-based compounds on critical molecular and cellular events associated with the pathophysiology of in-stent restenosis are discussed in detail with the conclusion that both sirolimus and paclitaxel are different in their pleiotropic anti-restenotic effects. This may be in part responsible for the differences observed in recent clinical studies.

Topics: Apoptosis; Cell Proliferation; Coronary Restenosis; Endothelium, Vascular; Humans; Muscle, Smooth, Vascular; Paclitaxel; Sirolimus; Stents

In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic compounds have been used in human clinical trials with disappointing outcomes. Little is known concerning potential adverse effects on vessel wall integrity and (re)healing, atherosclerotic lesion formation, progression, and plaque stability of these DES. Although efficacy and safety need to be determined clinically, preclinical testing of candidate drugs in well-defined animal models is extremely helpful to gain insight into the basic biological responses to candidate compounds. Here, we discuss and report an animal model which enables rapid screening of candidate drugs for DES on an atherosclerotic background. The results from drug testing using this novel model could help to quickly and cost-effectively establish the dose range of candidate drugs with reasonable potential for DES.

Topics: Animals; Atherosclerosis; Coronary Restenosis; Disease Models, Animal; Drug Delivery Systems; Drug Evaluation, Preclinical; Humans; Mice; Paclitaxel; Sirolimus; Stents

Drug-eluting stents have revolutionized the field of interventional cardiology and have provided a significant innovation for preventing coronary artery restenosis. Polymer coatings that deliver anti-proliferative drugs to the vessel wall are key components of these revolutionary medical devices. This article focuses on the development of stents which elute the potent anti-proliferative agent, zotarolimus, from a synthetic phosphorylcholine-based polymer known for its biocompatible profile. Zotarolimus is the first drug developed specifically for local delivery from stents for the prevention of restenosis and has been tested extensively to support this indication. Clinical experience with the PC polymer is also extensive, since more than 120,000 patients have been implanted to date with stents containing this non-thrombogenic coating. This review provides background on pre-clinical studies with zotarolimus, on the development of the biocompatible PC polymer and on the clinical trials conducted using two stent platforms which deliver this drug to patients with coronary artery disease.

Topics: Coronary Restenosis; Drug Delivery Systems; Humans; Randomized Controlled Trials as Topic; Sirolimus; Stents

Percutaneous coronary intervention has been hampered by restenosis since its inception. Many research projects including the use of various devices and systemic drug administration have shown disappointing results. Recently, the advent of drug-eluting stents has reduced incidence of restenosis compared with bare metal stents. This article provides an overview of the developments of drug-eluting stents, their clinical impact on the treatment of acute coronary syndrome, and their future perspectives.

Topics: Angina, Unstable; Animals; Clinical Trials as Topic; Coronary Restenosis; Drug Delivery Systems; Humans; Myocardial Infarction; Paclitaxel; Prognosis; Sirolimus; Stents; Syndrome

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Cost-Benefit Analysis; Drug Delivery Systems; Follow-Up Studies; Humans; Immunosuppressive Agents; Meta-Analysis as Topic; Mortality; Myocardial Infarction; Odds Ratio; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Time Factors

The goal of this study was to use angioscopy to investigate the amount of neointimal coverage after sirolimus-eluting stent (SES) implantation.. Sirolimus-eluting stents reduce intimal hyperplasia.. We used angioscopy to evaluate 37 consecutive stented coronary artery lesions (15 SES and 22 bare-metal stents [BMS]) in 25 patients (18 men, 7 women) at 3 to 6 months after stent implantation. Angioscopic evaluation focused on: 1) neointimal coverage of stent struts, and 2) the existence of thrombi. The degree of neointimal coverage was classified as grade 0 when there was no neointimal coverage (similar to immediately after the implantation); grade 1 when stent struts bulged into the lumen, but were covered and still translucently visible; grade 2 when stent struts were visible but not clearly seen (not translucent); and grade 3 when stent struts were not visible because they were embedded in the neointima.. Thrombi were identified in eight stented segments, tended to be more common with SES (p = 0.14), but were not seen on angiography. Three of the 15 SES (20%) had grade 0 neointimal coverage, and only 2 SES (13.3%) had complete coverage (grades 2/3). In contrast, all 22 BMS showed complete intimal coverage (grades 2/3). Thrombi were more common in stents with incomplete neointimal coverage (p = 0.09).. The SES had incomplete neointimal coverage three to six months after implantation, and this was associated with subclinical thrombus formation.

Topics: Aged; Angioscopy; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Delayed-Action Preparations; Female; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Stents; Tunica Intima; Wound Healing

Interventional cardiologists have quickly replaced bare metal stents with intravascular drug-eluting stents for treating and preventing restenosis, largely on the basis of empirical evidence that shows profound reduction in angiographic and clinical restenosis. A critical reassessment of the published evidence, however, suggests that the putative superiority of intravascular drug-eluting stents is founded on questionable premises, including 1) overestimation of restenosis benefit, 2) underestimation of the risk for stent thrombosis, 3) overreliance on "soft" rather than "hard" outcomes (need for repeated revascularization vs. death or myocardial infarction), and 4) the attendant overestimation of cost-effectiveness. Because the long-term incremental risks, benefits, and costs of drug-eluting stents have not yet been optimally evaluated in a broad spectrum of patient and lesion cohorts, the rational role of these devices in clinical management warrants reappraisal.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Cost-Benefit Analysis; Drug Delivery Systems; Equipment Design; Humans; Paclitaxel; Radiography; Randomized Controlled Trials as Topic; Sirolimus; Stents; Thrombosis

The purpose of this research was to determine the relative safety and efficacy of multiple (> or =2) overlapping Cypher sirolimus-eluting stents (SES) (Johnson & Johnson, New Brunswick, New Jersey).. Overlapping coronary stents are common. The periprocedural and late clinical and angiographic consequences of overlapped coronary stents are not clearly defined, particularly for drug-eluting stents.. All patients enrolled into five clinical trials of the SES were analyzed. Three of these trials were prospective randomized comparisons of the SES to the bare-metal stent (BMS), and two were prospective non-randomized trials of SES-treated patients with historical controls. All clinical and angiographic outcomes in overlap-stent-treated patients were compared by stent type and with single-stent-treated patients for the same stent device.. In all, 575 patients with stent overlap (337 SES, 238 BMS) and 1,162 patients with single stents (697 SES, 465 BMS) were analyzed. Stent overlap was associated with a greater late lumen loss in stent and more frequent angiographic restenosis regardless of stent type. Among overlap-stent-treated patients, the SES provided similar magnitude of restenosis benefit as observed for single-stent-treated patients. Overlapped SES was not associated with an increase in myocardial infarction.. The strategy of SES overlap, when required, is both safe and efficacious in reducing restenosis with no increase in the incidence of myocardial infarction or major adverse cardiovascular events, when compared with a bare metal coronary stent prosthesis.

Topics: Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Creatine Kinase; Humans; Metals; Middle Aged; Sirolimus; Stents

Percutaneous coronary intervention with drug-eluting stents is currently the preferred approach to the treatment of obstructive coronary stenoses. Large, randomized trials have demonstrated a significant reduction in the incidence of restenosis after drug-eluting stent placement compared with balloon angioplasty or bare metal stents across a wide range of lesions. Furthermore, these stents have appeared to be effective in maintaining the luminal patency at follow up for up to 2-4 years. Concerns regarding the potential adverse effects of drug-eluting stents, such as aneurysm formation in arteries secondary to drug toxicity or hypersensitivity, as well as the overdependence on antiplatelet therapy for a protracted period to prevent subacute thrombosis, have been raised. However, evidence from large studies has not demonstrated any significant increase in the incidence of such adverse events. Future approaches to treating coronary stenoses involve technical modifications, such as direct stenting, accelerating endothelialization with gene delivery of nitric oxide donors, smooth muscle cell growth inhibitors after stent placement, biodegradable stents and concurrent use of local molecule delivery and oral chemotherapy. Ongoing large-scale postmarketing surveillance studies are expected to provide credible answers to the concerns regarding the safety of these stents.

Topics: Animals; Antineoplastic Agents, Phytogenic; Brachytherapy; Clinical Trials as Topic; Coronary Restenosis; Endothelium, Vascular; Humans; Immunosuppressive Agents; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Tissue Engineering

Despite considerable benefits associated with current drug-eluting stents (DES), continued attention to the safety, efficacy, and deliverability of first-generation DES has led to the development of new antiproliferative agents with alternative stent platforms and different drug carrier systems. Zotarolimus is a recently developed pharmacologic agent with both antiproliferative and anti-inflammatory properties. The Endeavor drug-eluting stent (Medtronic Vascular, Santa Rosa, CA) represents the combination of zotarolimus, a low-profile cobalt alloy stent platform, and a biocompatible phosphorylcholine drug carrier system. At present, four clinical trials examining the safety and efficacy of the Endeavor stent have been performed. Although these studies have enrolled patients with similar clinical and angiographic characteristics, they have differed in trial design and study population size and have been performed across a broad geographic and physician distribution. Despite these differences, the results of these trials demonstrate consistently low rates of angiographic restenosis and repeat revascularization in addition to a favorable safety profile, with no occurrences of late stent thrombosis through 1 year of follow-up. This review describes the pharmacology and design on the Endeavor stent, summarizes results from recent clinical trials evaluating the Endeavor stent, and provides an overview of ongoing and future directions for clinical investigation.

Topics: Anti-Inflammatory Agents; Blood Vessel Prosthesis Implantation; Clinical Trials as Topic; Coated Materials, Biocompatible; Combined Modality Therapy; Coronary Restenosis; Coronary Stenosis; Humans; Phosphorylcholine; Prosthesis Design; Sirolimus; Stents

The CYPHER (Cordis, Johnson & Johnson) sirolimus-eluting stent and the TAXU (Boston Scientific) paclitaxel-eluting stent have been extensively evaluated and have been proven to be significant novel tools for the treatment of coronary artery disease. Several sirolimus derivatives have already emerged, receiving CE Mark approval. However, in the future, it is likely that drugs presently under investigation will address additional mechanisms associated with neointimal formation, either as single agents or in combination with antiproliferative compounds. Concurrently, alterations on stent platform design (helicoidal, open-closed cell), coatings (biodegradable, bioabsorbable, nanoporous) and polymers are being explored.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Diseases; Coated Materials, Biocompatible; Coronary Restenosis; Equipment Design; Humans; Paclitaxel; Sirolimus; Stents

Restenosis after percutaneous intervention in the left main coronary artery may present as sudden cardiac death. Although drug-eluting stents have demonstrated promising results, there remains the question about appropriate length of the left main artery to be covered with the stent. We describe a patient who received two drug-eluting stents with the balloon crushing technique in the distal left main coronary artery. Three months later, this patient presented with a new lesion in the segment of the left main artery not covered with stent, but instead at the site where the balloon was inflated in the initial procedure.

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheterization; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug Delivery Systems; Female; Humans; Middle Aged; Retreatment; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Treatment Outcome

We present the case of a 75-year-old female who developed restenosis after the deployment of kissing sirolimus-eluting stents at the left main coronary artery (LMCA) bifurcation. Restenosis occurred at the left circumflex (LCx) artery ostium, where a stent deployed from the LMCA to the LCx arteries overlapped another stent deployed from the LMCA to the left anterior descending (LAD) artery. We investigated the stent expansion and deformation after kissing stent implantation using a phantom three-dimensional model depicting a LMCA bifurcation. Stent overlap was detected at the distal LMCA whether the LAD stent was positioned over the left circumflex (LCx) stent or vice versa. Stent overlap created a gap beneath the overlapped portion of the stent. Thus, we found that kissing stent implantation using different-sized stents produced compression of the LCx stent at the distal LMCA. Incomplete stent apposition caused by stent overlap and stent deformation is thought to be the main mechanism for restenosis after kissing stent implantation procedures.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheterization; Coronary Angiography; Coronary Restenosis; Equipment Design; Equipment Failure Analysis; Equipment Safety; Female; Follow-Up Studies; Humans; Myocardial Infarction; Retreatment; Sirolimus; Stents; Treatment Outcome

Cypher (sirolimus-eluting stent) and Taxus (paclitaxel-eluting stent) have been approved for use in percutaneous coronary intervention. Both of the stents have shown superiority over bare metal stents in reducing major adverse cardiac events, restenosis rates and target vessel revascularisation. Results of clinical trials with head-to-head comparison of Taxus and Cypher stents in patients with obstructive coronary artery diseases have recently been reported. This review compares the performance of Cypher and Taxus stents as noted in observational studies and clinical trials in various types of coronary artery lesions.

Topics: Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Combined Modality Therapy; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Diabetes Complications; Drug Implants; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Although drug-eluting stents have assumed a dominant role in interventional cardiology, concern has been raised about the potential for long-term adverse outcomes, including death. The aim of the present study was to compare the incidence and cause of death between patients who received sirolimus-eluting or bare metal stents.. An integrated analysis was performed on 1748 patients enrolled in four prospective double-blind trials that randomly assigned patients to receive either a sirolimus-eluting or a bare metal stent for treatment of a single de novo coronary stenosis. During a mean follow-up of 2.6+/-0.6 years, 64 patients (3.7%) died. Total mortality was 3.2% among 870 bare metal stent patients and 4.1% among 878 sirolimus-eluting stent patients (P=0.37); there was no difference in cardiac mortality (1.4 vs. 1.3%; P=0.55) or causes of death between these two groups. The predominant cause of death was non-cardiac. Cardiac death was most frequently assigned owing to unwitnessed death. Death due to acute myocardial infarction, congestive heart failure, and stent thrombosis occurred infrequently.. At a mean follow-up of 2.6 years in percutaneous coronary intervention patients, the predominant cause of death was non-cardiac. There was no significant difference in either the frequency or the cause of death with implantation of either sirolimus-eluting or bare metal stents.

Topics: Aged; Cause of Death; Coronary Restenosis; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Immunosuppressive Agents; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Regression Analysis; Sirolimus; Stents

Drug-eluting stent technology consisting of a bare metal stent, carrier coating, bioactive drug and delivery system, offers an almost infinite range of possible device configurations. A growing understanding of the mechanisms of restenosis allows for the design of synergistic functions within these components, thus providing a basis for new and improved products. The BioMatrix stent (Biosensors Interventional Technologies Pte Ltd., Singapore) elutes the new sirolimus derivative Biolimus A9 from a biodegradable polylactic acid polymer. Biolimus A9 possesses enhanced anti-inflammatory and antiproliferative activity with an improved pharmacokinetic profile. Permanent polymer-carrier-based platforms may be associated with inflammation, late thrombosis and restenosis. The BioMatrix, with its asymmetric and abluminal coating, releases Biolimus A9 into the vessel wall while the polylactic acid polymer is resorbed by surrounding tissues. Clinical studies have demonstrated the BioMatrix to be well tolerated and effective, and it has now become the subject of an aggressive clinical program.

Topics: Animals; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Drug Carriers; Drug Delivery Systems; Humans; Lactic Acid; Polyesters; Polymers; Randomized Controlled Trials as Topic; Sirolimus; Stents

The first method of percutaneously treating a diseased vessel was developed by Dotter and Judkins in 1964. Andreas Grüntzig performed the first coronary angioplasty in 1977. In 1985 Palmaz et al. implanted the first balloon-mounted stent in a peripheral artery. Puel and Sigwart implanted the first human coronary stent in March 1986; it was a self-expanding mesh-like device. Schatz et al. applied some small modifications to the original Palmaz stent, which resulted in the first coronary stent available on the market, called Palmaz-Schatz stent. In 1987 Sigwart was the first to suggest the use of coronary stents in acute vessel occlusions during unsuccessful PTCA. Using the device it became possible to cover the intimal flap and to prevent elastic recoil. Because of the high incidence of subacute stent thromboses and the bleeding complications (aggressive anticoagulation regimens) these times the coronary stents were implanted only in order to avoid emergency CABG surgery. In 1993 BENESTENT and STRESS trials have proved that elective stent implantation can significantly reduce the incidence of restenosis. The dual antiplatelet therapy and the high pressure stent implantation technique dramatically reduced the incidence of subacute stent thrombosis. The treatment of coronary artery disease has undergone revolutionary changes in the past decade but remained the leading cause of mortality in the developed world. The most important limitation of PCI has been in-stent restenosis, which occurs in 20-40% of stent implantations. Clinically it results in recurrent ischemic episodes most often requiring repeat revascularisation (rePCI or CABG). With the use of drug-eluting stents the incidence of in-stent restenosis can be reduced dramatically, based on the currently available clinical trials it remains below 10%.

Topics: Cell Cycle; Cell Proliferation; Coronary Artery Disease; Coronary Restenosis; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Hungary; Muscle, Smooth, Vascular; Paclitaxel; Protein Kinases; Sirolimus; Stents; TOR Serine-Threonine Kinases; Treatment Outcome; Tubulin Modulators; United States

This meta-analysis was conducted to compare the effects of drug (paclitaxel and sirolimus)-eluting stents with bare metal stents on major adverse cardiac events, restenosis rates and late loss of arterial lumen diameter in patients with obstructive coronary artery disease.. Randomized, controlled clinical trials comparing sirolimus- and paclitaxel-eluting stents with bare metal stents were identified through electronic and manual search. Fixed effects method of Mantel-Haenszel and random effects method of DerSimonian and Laird were used for computing the pooled odds ratio (OR) and 95% confidence intervals (CI) for major adverse cardiac events and restenosis rates. Standardized mean difference with 95% CI was calculated for late-loss of arterial lumen diameter.. A total of 13 studies were included in the meta-analysis. As compared with bare metal stents, the use of sirolimus- and paclitaxel-eluting stents significantly reduced the major adverse cardiac events (pooled OR 0.35; 95% CI 0.24-0.50), restenosis rates (pooled OR 0.27; 95% CI 0.15-0.47), and late loss of arterial lumen diameter (mean difference 0.57 mm, 95% CI 0.49-0.68).. Paclitaxel- and sirolimus-eluting stents significantly reduced the incidence of major adverse cardiac events, restenosis rates, and late loss of arterial lumen diameter as compared with bare metal stents.

Topics: Cell Proliferation; Coronary Restenosis; Coronary Stenosis; Death, Sudden, Cardiac; Drug Implants; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome; Tunica Intima

For patients with coronary artery disease undergoing percutaneous intervention, drug-eluting stents (DESs) have rapidly become the standard of care. This article reviews the currently available delivery-platform/drug-carrier-vehicle combinations and those expected to become available in the future. It also evaluates and compares current DES platforms in terms of the drug involved, the delivery platform, efficacy, and safety. Currently, 2 DES platforms are available: 1 eluting sirolimus and 1 eluting paclitaxel. Sirolimus is a macrolide antibiotic with a cytostatic mechanism and an anti-inflammatory effect. Paclitaxel is a chemotherapeutic (cytotoxic) agent. The delivery platform is composed of the balloon catheter, the stent, and the drug-carrier vehicle. The carrier vehicle offers controlled drug release and enhances drug distribution. It can be a polymer that serves as a diffusion barrier or a matrix (either durable or degradable) for drug loading. Alternatively, a structural modification on the surface of the stent itself, such as a groove or well in which the drug is placed, can serve as carrier. With respect to efficacy, major trials have shown that the sirolimus platform has a lower late luminal loss rate than does the paclitaxel stent. Moreover, less intimal proliferation and obstruction occurs with the sirolimus platform than with the paclitaxel platform. Also, compared to bare metal stents, the sirolimus platform reduces late luminal loss in challenging subsets of patients. Both stents offer excellent short-term safety. To improve our understanding of these stents, a head-to-head comparison is needed.

Topics: Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Humans; Immunosuppressive Agents; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Time Factors

Topics: Antineoplastic Agents, Phytogenic; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Equipment Design; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

The two pivotal U.S. trials of drug-eluting stents do not establish the principle that these stents are superior to thin-strut bare-metal stents for preventing repeat revascularization in patients with diabetes. Neither study was adequately powered to make this determination. Moreover, both studies used thick-strut stents known to have high restenosis rates as controls. Low angiographic follow-up underestimates the true target lesion revascularization rate in the Polymer-Based Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease (TAXUS-IV) trial because of the high incidence of silent ischemia in patients with diabetes. Optimal therapy for diabetic coronary disease should include a comprehensive approach directed toward metabolic normalization in addition to local stent-based therapy.

Topics: Clinical Trials as Topic; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetic Angiopathies; Drug Delivery Systems; Humans; Paclitaxel; Sirolimus; Stents

Topics: Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Follow-Up Studies; Humans; Observation; Randomized Controlled Trials as Topic; Sirolimus; Stents; Surface Properties

Topics: Angioplasty; Antineoplastic Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Humans; Immunosuppressive Agents; Paclitaxel; Polymers; Sirolimus; Stents; Thrombosis

The implantation of intracoronary stents for the treatment of coronary atherosclerotic disease is one of the most common percutaneous procedures. While the procedure brings long-term benefit for a large percentage of patients, a significant number of patients experience in-stent restenosis (ISR). ISR may be caused by a number of biological and procedural factors, including lesion characteristics as well as co-existing disease states like diabetes. Many strategies have been developed to try to reduce the incidence of ISR. The primary methods include systemic pharmacologic treatments, as well as attempts at modifying stents to reduce their role in the development of ISR. Drug-eluting stents are one such modality, and are expected to become a widely used tool in the field of interventional cardiology. This review will focus on the pathophysiology of ISR and possible ways to prevent it, including drug-eluting stents.

Topics: Anticoagulants; Antineoplastic Agents; Coated Materials, Biocompatible; Coronary Restenosis; Delayed-Action Preparations; Humans; Sirolimus; Stents; Steroids

Randomized trials comparing drug-eluting stents (DES) with bare-metal stents have shown that the former significantly reduce the incidence of angiographic and clinical restenosis into an unprecedented low, one-digit, range. However, post-DES restenosis is not zero. Next to incomplete coverage with DES of the vessel segment injured by balloon angioplasty, factors such as stent underexpansion, stent overexpansion, and nonuniform distribution of stent struts have been associated with post-DES restenosis. Current evidence suggests that inadequate, though predominantly focal, delivery of the antiproliferative agent (sirolimus or paclitaxel) into the vessel wall is likely the common cause of post-DES restenosis. There is no consensus at present on how to treat post-DES restenosis. Long-term results reported to date on small numbers of patients undergoing interventional treatment for post-DES restenosis appear to be worse than outcomes observed after the index intervention, regardless of whether another DES was implanted or not, and warrant further study.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Failure; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antineoplastic Agents, Phytogenic; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Polymers; Sirolimus; Stents; Thrombosis; Warfarin

This meta-analysis combined the results of randomized clinical trials to compare the efficacy of drug-eluting stents with that of bare metal stents in percutaneous coronary interventions to ascertain which revascularization strategy is most safe and effective. The literature identified 13 published studies, and 8 were included in the main meta-analysis, thus allowing a meta-analysis on 3,860 patients for the effect on all major adverse clinical events (MACEs) combined and for target vessel revascularization. Meta-analyses were performed for combined MACEs, patient MACEs, and thrombosis. Regression meta-analyses were performed to examine the effect of certain variables on the efficacy of drug-eluting stents compared with bare metal stents. Meta-analysis of all trials showed that drug-eluting stents produced significant decreases in the need for percutaneous revascularization (relative risk [RR] 0.30, 95% confidence interval [CI] 0.22 to 0.40) and coronary artery bypass grafting (RR 0.54, 95% CI 0.32 to 0.89). Drug-eluting stents significantly decreased all MACEs combined (RR 0.40, 95% CI 0.33 to 0.49) but were not associated with an increased risk of stent thrombosis or death. These results were confirmed at analysis as stratified by type of eluting stent, because the need for percutaneous revascularization was significantly lower for sirolimus-eluting stents (RR 0.23, 95% CI 0.15 to 0.35) and paclitaxel-eluting stents (RR 0.39, 95% CIl 0.29 to 0.53).

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Humans; Immunosuppressive Agents; Paclitaxel; Radiography; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Emplacing a stent in the coronary artery has many characteristics. The installation is easy to do and the stent has evident curative effect. However, it will cause thrombosis and immunoreaction because it is metal. So suburgent thrombosis and restenosis after surgeries are still two major complications. The drug-coated stent is one kind of the drug-eluting stents, whose metal surface is coated by some polymer that combines with a sort of effective drug or antibody. It can transport the drug or antibody to the localily of pathological changes and there in it improves the local drug concentration. In this paper the research progress of interrelated issues about the drug-coated stent is reviewed.

Topics: Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Restenosis; Drug Delivery Systems; Humans; Lactic Acid; Paclitaxel; Pharmaceutical Preparations; Polyesters; Polymers; Sirolimus; Stents

Local stent-based drug delivery (drug-eluting stent - DES) is a new technology aimed to prevent the development of neointimal hyperplasia and restenosis following percutaneous coronary interventions. A number of DESs have been developed using different carrier stents, different kind of coatings, and different drugs. However, to date only two polymer-coated DESs (the Cypher sirolimus-eluting stent from Cordis, Johnson & Johnson, Miami Lake, FL, USA; and the Taxus paclitaxel-eluting stent, Boston Scientific, Natick, MA, USA) have become commercially available after a number of randomized trials showed their ability to reduce late luminal loss, binary restenosis and the need for repeat revascularization when compared to bare metal stents. This review describes the general concept of DES and summarizes the results of the principal clinical trials on DESs, both approved for clinical use or under development. For the marketed stents, we also report the results of the first clinical evaluations in real life and a few insights into the most controversial issues.

Topics: Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Female; Humans; Male; Paclitaxel; Prognosis; Radiography; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Sirolimus; Stents; Treatment Outcome

Topics: Coronary Restenosis; Drug Implants; Equipment Failure; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

Drug-eluting stents prevent in-stent restenosis after percutaneous coronary intervention, and differences between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) may exist in the rates of target lesion revascularization, death, myocardial infarction and stent thrombosis.. To compare the efficacy of SES and PES with the efficacy of bare-metal stents for de novo coronary lesions in patients with stable or unstable angina.. A meta-analysis of randomized trials from MEDLINE, EMBASE and other electronic databases and conference proceedings was conducted. The efficacy of SES, PES with a polymer carrier (PPOL) and PES without a polymer carrier (PNPOL) was compared using random-effects models.. Ten trials comprising 5041 patients were included in the meta-analysis. There was an absolute decrease in target lesion revascularization of 17% (95% CI 14% to 20%), 9% (95% CI 6% to 11%) and 3% (95% CI 0% to 6%) with SES, PPOL and PNPOL, respectively, with significant differences between SES and PPOL and between PPOL and PNPOL (P < 0.01 for both comparisons). However, sensitivity analysis using the OR of target lesion revascularization showed no difference between SES (OR 0.18 [95% CI 0.12 to 0.26]) and PPOL (OR 0.25 [95% CI 0.16 to 0.37]) (P = 0.26). There were no differences in the incidence of death, myocardial infarction or stent thrombosis, although the small number of events limited the power of these analyses.. SES show a greater absolute reduction in target lesion revascularization than do PES, likely due to differences in the bare-metal stents used for comparison in the trials. Head-to-head comparisons are needed to directly address the differential efficacy of SES and PES.

Topics: Age Factors; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Dose-Response Relationship, Drug; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prognosis; Randomized Controlled Trials as Topic; Severity of Illness Index; Sex Factors; Sirolimus; Stents; Survival Analysis; Treatment Outcome

All percutaneous interventions disrupt atherosclerotic plaque and denude the endothelium. These processes stimulate both platelet aggregation and the coagulation cascade. Therefore, pharmacological treatment during percutaneous intervention is based on the use of antithrombotic agents. In addition to aspirin, whose benefit has been clearly demonstrated in all forms of ischemic heart disease, clopidogrel, given before and after cardiac catheterization, also reduces the rate of thrombosis after stent placement. Moreover, the introduction of glycoprotein IIb/IIIa inhibitors has improved the results of percutaneous revascularization, especially in high-risk patients. On the other hand, anticoagulants are essential for preventing the acute thrombotic complications that result from the invasive nature of the procedure. Low-molecular-weight heparins, direct thrombin inhibitors (e.g., hirudin and its derivatives), and recently developed pentasaccharides, which inhibit factor X, provide new alternatives to classical unfractionated heparin. These novel compounds lead to fewer hemorrhagic complications than unfractionated heparin and do not require such extensive monitoring. Finally, new antiproliferative agents, such as oral rapamycin, have been introduced to reduce the rate of coronary restenosis during follow-up.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Anticoagulants; Cardiac Catheterization; Clopidogrel; Coronary Restenosis; Factor X; Fibrinolytic Agents; Follow-Up Studies; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Immunosuppressive Agents; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Stents; Thrombolytic Therapy; Thrombosis; Ticlopidine; Time Factors

Coronary stents are currently used in most percutaneous coronary interventions, since they have demonstrated to reduce restenosis and allow to solve threatened closure after balloon angioplasty. Despite these beneficial effects, restenosis remains as the main limitation of percutaneous coronary interventions even with the use of coronary stents. In the last 3 years, some coronary stents eluting anti-proliferative drugs have demonstrated to dramatically reduce the risk of restenosis. By November 2004, two different types of antiproliferative drugs eluted by coronary stents are commercially available: sirolimus (rapamycin) and paclitaxel. The mechanisms, clinical evidence, as well as the remaining limitations of these drug-eluting stents are reviewed. The current knowledge of other anti-proliferative drugs that are currently under investigation is also reviewed.

Topics: Cell Proliferation; Coronary Restenosis; Humans; Paclitaxel; Sirolimus; Stents

The only widely accepted way to reduce restenosis rate after percutaneous balloon angioplasty has been the use of coronary bare metal stents, and the last decade has witnessed a prompt and widespread adoption of bare metal stents that has revolutionized the field of interventional cardiology. The new millennium has seen the recent development of drug-eluting stents (DES), allowing controlled release of a drug directly to the injured artery, which seem to have prevented by large the problem of in-stent restenosis. The goal of this review was to summarize recent laboratory and clinical investigations concerning the effects of DES in various settings relevant to coronary heart disease. In the experimental setting, we examine the intracellular signaling and the role of smooth muscle cells after vascular injury. We also discuss recent observations from our laboratory showing the effects of coating per se on cell apoptosis and proliferation. In the clinical setting, the effects of DES in patients with stable or unstable angina pectoris is examined in detail for the relevant implications both in the treatment and prognosis. The results of a meta-analysis on the effects that have been overlooked in individual studies are reported which show a striking reduction in bypass surgery after DES implantation. Finally, we discuss the potential role of new materials and technologies (i.e., nanotechnology) that will improve DES performance allowing other future clinical applications in patients with ST-elevation myocardial infarction, vulnerable plaques, insulin-dependent diabetes mellitus, etc.

Topics: Animals; Antineoplastic Agents, Phytogenic; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Humans; Immunosuppressive Agents; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Sirolimus; Stents

Despite recent advances, the in-stent restenosis (ISR) remains a challenging problem in interventional cardiology with an estimated overall restenosis rate of 20%, 25-30% in bare metal stents and 12% in drug-eluting stents (DES). In this review, we provide an overview of therapeutic options which include balloon angioplasty, cutting balloon, debulking techniques, brachytherapy and DES. Intracoronary brachytherapy using beta or gamma radiation had been considered the standard of care for some years. However, the use of DES to treat ISR has been shown to be safe, effective and ease-of-use for the prevention of recurrent restenosis. ISR after DES when focal angiographic pattern is present can be often treated with balloon angioplasty whereas if a non-focal pattern is recognized a new DES implantation is indicated. Waiting for a definitive answer regarding the optimal treatment of ISR from ongoing trials, we present our current approach to ISR.

Topics: Antineoplastic Agents, Phytogenic; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Humans; Immunosuppressive Agents; Myocardial Revascularization; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Restenosis remains as the main limitation of percutaneous coronary intervention, even in the era of coronary stents. Recently, drug-eluting stents have been shown to reduce significantly both the rate of in-stent restenosis and the need for subsequent revascularization procedures compared with bare-metal stents. At present, these beneficial effects have been demonstrated mainly with Cypher (Cordis Corporation) and Taxus (Boston Scientific) stents. They persist for at least 3 years after implantation. Although the results of some complex clinical angiographic studies are still awaited, all the indications suggest that use of this type of stent will become standard in percutaneous coronary interventions in the future. With regard to other techniques, intracoronary brachytherapy is effective only for the treatment of in-stent restenosis. The recent withdrawal from the market of brachytherapy catheters means that the technique has effectively disappeared from the interventional cardiologist's armamentarium, at least in our setting. Other devices, especially rotational atherectomy catheters and cutting balloons, will survive in the era of drug-eluting stents as they facilitate stent implantation in particularly complex lesions.

Topics: Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Atherectomy, Coronary; Brachytherapy; Coronary Restenosis; Delayed-Action Preparations; Forecasting; Humans; Immunosuppressive Agents; Paclitaxel; Polymers; Randomized Controlled Trials as Topic; Sirolimus; Stents; Time Factors

Restenosis is a major limitation to the long-term success of percutaneous coronary intervention. Drug-eluting stents are the most recent technological advance in restenosis prevention. While they are effective, their use is associated with a significant incremental cost, and a recent economic evaluation performed by the authors suggested that their use is associated with a cost per quality-adjusted life year of $58,721. How should decision-makers react to this value, particularly given that the use of sirolimus-eluting stents appears more attractive in certain patient subgroups, such as those with complex coronary lesions? In the present paper, the authors explore an alternative method of presenting the results of their economic evaluation, rather than the usual cost per quality-adjusted life year rubric, in an attempt to assist decision-makers in deciding whether, and for whom, to fund sirolimus-eluting stents. Several issues that decision-makers and providers may wish to consider when making such funding decisions are discussed.

Topics: Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Cost-Benefit Analysis; Humans; Immunosuppressive Agents; Models, Economic; Quality of Life; Sirolimus; Stents; Treatment Outcome

Drug eluting stents have been developed in order to reduce in-stent restenosis observed with a 20 to 40% rate in bare-stents. Neoinitimal smooth muscular cells proliferation have been characterized as the corner stone of in-stent restenosis. Consequently, many anti-mitotic and anti-inflammatory drugs have been evaluated in a new stent generation, so called coated stents or drug eluting stents. Three major components must be considered to evaluate the beneficial effects: the bare-stent, the drug, and the deliverance system, most usually a polymer. For the present, sirolimus eluting stent and paclitaxel eluting stent are available in the market with the european conformity label considering evidence based medicine established in randomized trials. Both stents have been shown to reduce in-stent restenosis incidence to less than 7%. Long-term follow-up still remain expected and would give answers to two safety queries: what is about the incidence of late stent thrombosis, what is about mal-apposition consequences in clinical feature. Utilization of drug eluting stent in clinical practice must considered materials with european conformity and must applied French society of cardiology guidelines restricting implantation to patients who meet high-risk restenosis criteria. Medicoeconomic approach must be considered beneficial at the present only in patients with high restenosis risk. Long-term antiplatelet regimen of aspirin and clopidogrel must be considered to avoid late stent thrombosis.

Topics: Clinical Trials as Topic; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; ortho-Aminobenzoates; Paclitaxel; Platelet Aggregation Inhibitors; Sirolimus; Stents; Tacrolimus

The sirolimus-eluting stent has been studied extensively in randomized controlled trials of patients with native de novo coronary lesions. Lesion predilation before stent placement has been the predominant implantation strategy in these trials. Direct implantation of the sirolimus-eluting stent without lesion predilation has been undertaken at the investigators' discretion in certain trials as well as in patients enrolled in a post-marketing surveillance registry, and was the intended implantation strategy in the DIRECT trial. Comparisons with patients receiving sirolimus-eluting stents after lesion predilation in the trials and the registry were all confounded by imbalances in patient, lesion, and/or procedural characteristics and point to the highly selective nature of the direct-stenting strategy. At present, direct implantation of the sirolimus-eluting stent appears to be safe and as effective as conventional (predilated) stenting, provided that the targeted coronary lesion is amenable to the direct approach. Since a randomized trial of implantation strategies is lacking, there is no conclusive evidence as to the hypothesized superiority of direct over predilated stenting in suitable coronary lesions.

Topics: Cell Proliferation; Coronary Restenosis; Humans; Muscle, Smooth, Vascular; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Sirolimus; Stents

This article briefly reviews the causes of restenosis and the current strategies for preventing and treating restenosis after percutaneous coronary intervention. Interventions such as intracoronary radiation and drug-eluting stents are discussed.

Topics: Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Restenosis; Humans; Paclitaxel; Sirolimus; Stents

Restenosis is a direct result of vessel injury, local inflammation, and remodeling following balloon angioplasty and coronary stenting resulting in luminal narrowing. The process involves a complex interplay of released growth factors that stimulate smooth muscle cells (SMCs) to migrate and proliferate, as well as activating endothelial cells (ECs) at injury sites. The latter re-establishes the luminal endothelial monolayer that keeps a barrier to circulating cells from underlying extracellular matrix and SMCs. Understanding the cellular mechanisms of intimal hyperplasia and re-endothelialization is important in that uncontrolled cellular processes account for coronary luminal narrowing, leading to the recurrence of clinical symptoms, hospitalizations, and repeat interventions. The evolution of drug-eluting stents that inhibit intimal hyperplasia has revolutionized percutaneous coronary interventions in that potential late luminal narrowing is attenuated. Sirolimus and paclitaxel are two medications utilized for their efficacy at inhibiting intimal hyperplasia and subsequent clinical events. The effects of these drugs on EC biology have not been well investigated. This article discusses basic cellular processes of vessel repair after balloon angioplasty and stenting, and focuses on the differential molecular mechanisms of sirolimus and paclitaxel towards proliferation and migration. These drugs inhibit both SMC and EC proliferation, but by different mechanisms, and paclitaxel inhibits EC migration, whereas sirolimus does not. Their discriminating effects towards re-endothelialization may clinically differentiate these two drugs. Inhibiting re-endothelialization may translate into more adverse clinical events.

Topics: Antineoplastic Agents, Phytogenic; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Vessels; Endothelium, Vascular; Humans; Hyperplasia; Immunosuppressive Agents; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Tunica Intima

The development of drug-eluting stents is one of the major revolutions in the field of Interventional Cardiology. Restenosis rate has been significantly reduced, in comparison to bare metal stents. The ideal drug to prevent restenosis must have an anti-proliferative and anti-migratory effect on smooth muscle cells but on the other hand must also enhance re-endothelialization, in order to prevent late thrombosis. Additionally, it should effectively inhibit the anti-inflammatory response after balloon induced arterial injury. Currently sirolimus, paclitaxel and more recently, ABT-578-eluting stents are commercially available, but ongoing research and clinical trials will result in new stents coming to market with novel designs loaded with a variety of compounds. As drug-eluting stent implantation becomes more liberal leading to an extensive use of this technology, the problem of restenosis in drug-eluting stents will become more common. However, for the time being, little is known regarding optimal treatment of in-stent restenosis following drug-eluting stent implantation. Future research is mandatory to further clarify, whether these patients should be treated with the same drug-eluting stent, with a different drug-eluting stent or with increased doses.

Topics: Coronary Restenosis; Drug Delivery Systems; Equipment Design; Humans; Sirolimus; Stents; Treatment Failure

The introduction of drug-eluting stents (DES) to interventional cardiology practice has resulted in a significant improvement in the long-term efficacy of percutaneous coronary interventions. DES successfully combine mechanical benefits of bare-metal stents and stabilizing the lumen, with direct delivery and the controlled elution of a pharmacologic agent to the injured vessel wall to suppress further neointimal proliferation. The dramatic reduction in restenosis has resulted in the implementation of DES in clinical practice, and has rapidly expanded the whole spectrum of successfully treatable coronary conditions, particularly in high-risk patients and complex lesions. In this review the authors present current data on DES. Currently, two types of DES are available in the USA: sirolimus-eluting stents (SES) CYPHER (Cordis Corp., FL, USA) and paclitaxel-eluting stents (PES) TAXUS (Boston Scientific, MA, USA), and many more are on the way to approval. In addition to sirolimus and paclitaxel, several other drugs have been successfully used in DES. Everolimus and ABT-578 are both analogs of sirolimus that also have immunosuppressive and antiproliferative properties. Another approach in the development of DES is to use drugs that can accelerate re-endothelialization and restore normal endothelial function following vascular injury. Recent advances in vascular gene transfer have also demonstrated potential new treatment modalities for cardiovascular disease, particularly in the treatment of vascular restenosis.

Topics: Clinical Trials as Topic; Combined Modality Therapy; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Fibrinolytic Agents; Humans; Paclitaxel; Prosthesis Design; Sirolimus; Stents

Clinical information regarding paclitaxel-eluting coronary artery stents is reviewed.. Restenosis is a significant complication of percutaneous coronary intervention. Coronary artery stenting has reduced restenosis compared with traditional balloon angioplasty, although restenosis still occurs with bare-metal coronary artery stents. The pathogenesis of in-stent restenosis is believed to involve smooth-muscle-cell proliferation and migration in response to vessel injury. A neointimal layer of extracellular matrix and collagen forms, which may impinge on the vessel lumen. Paclitaxel inhibits vascular smooth-muscle-cell proliferation and reduces neointimal mass. Local delivery of paclitaxel through a coronary stent has been shown to reduce restenosis rates and percent diameter stenosis and to produce other angiographic benefits compared with bare-metal stents. Fewer major adverse coronary events are seen with paclitaxel-eluting stents, predominantly because of a reduction in the need for target-vessel revascularization with minimal impact on rates of mortality and myocardial infarction (MI). The Taxus Express(2) stent, the only approved paclitaxel-eluting stent in the United States, costs about three times as much as a bare-metal stent. Cost-effectiveness analyses are needed to determine if the Taxus stent is cost-effective in clinical practice.. Paclitaxel-eluting stents reduce the rates of restenosis and target-vessel revascularization compared with bare-metal stents and have comparable effects on mortality and MI rates.

Topics: Antineoplastic Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Humans; Paclitaxel; Sirolimus; Stents

To compare the safety, effectiveness and cost-effectiveness of drug-eluting coronary stents used in Australia with bare-metal stents and determine whether the benefits are greater for high-risk subgroups.. MEDLINE, Pre-Medline, EMBASE, Current Contents, CINAHL and the Cochrane Library database were searched to identify eligible randomised controlled trials and systematic reviews published in English between January 1966 and June 2004.. Seven randomised controlled trials that assessed polymer-based paclitaxel- or sirolimus-eluting stents versus bare-metal stents in patients with coronary atherosclerosis and reported on stent thrombosis, mortality, myocardial infarction, coronary artery bypass grafting or target lesion revascularisation.. Two independent reviewers appraised eligible studies and extracted data. Relative risks (RRs) were calculated for each outcome and pooled using the Mantel-Haenszel method.. Rates of stent thrombosis, mortality, myocardial infarction and bypass grafts did not differ by stent type. Drug-eluting stents (DESs) resulted in a 71%-80% lower risk of revascularisation at 12 months (RR 0.29 [95% CI, 0.20-0.43] for paclitaxel-eluting stents [n = 1593 patients]; RR 0.20 [95% CI, 0.13-0.29] for sirolimus-eluting stents [n = 1296 patients]). Similar benefits were seen in several high-risk subgroups of patients: those with diabetes, lesion length > 20 mm and target-vessel diameter < or = 2.5 mm. The benefits of DESs in these high-risk groups over lower-risk groups were inconclusive because of low numbers. The cost per revascularisation avoided by using DESs was 3,750-6,100 Australian dollars, with an estimated cost per quality-adjusted-life-year (QALY) gained of 46,829-76,467 Australian dollars. In sensitivity analyses, estimates varied from DESs being cost-saving to costing an additional 314,385 Australian dollars per QALY gained.. DESs are effective in reducing revascularisation. Estimates of cost-effectiveness are very sensitive to changes in estimates of their true effects in clinical practice, market price and the number of stents used per patient. Decisions to limit DESs to only patients at the highest risk of restenosis may improve their cost-effectiveness but will need to be reassessed when evidence is available to compare absolute benefits between patient groups.

Topics: Australia; Coronary Restenosis; Coronary Stenosis; Cost-Benefit Analysis; Equipment Design; Humans; Immunosuppressive Agents; Metals; Paclitaxel; Patient Selection; Polymers; Risk; Sirolimus; Stents; Treatment Outcome

Drug-eluting stents (DESs) have revolutionized interventional cardiology over the past few years to the extent that balloon angioplasty and bare stents did in the 1980s and 1990s. The first DESs became commercially available in Europe in 2002 and in the US in 2003, and it is estimated that up to 80% of patients who undergo stent implantation in the US now receive a DES. Two devices, Cypher sirolimus-eluting stents (Cordis Corporation, Miami Lakes, FL) and Taxus paclitaxel-eluting stents (Boston Scientific Corporation, Natick, MN), are currently licensed for sale in both regions. Multiple new devices using different drugs, carriers and stents are currently undergoing clinical trials to establish their efficacy and obtain approval for commercialization. While the remarkable reduction of restenosis has accounted for the success of DESs, concerns remain regarding long-term follow-up; published 3-year follow-up results are available for fewer than 200 patients overall. Reports of late stent thrombosis have emerged, particularly in relation to discontinuation of antiplatelet therapy. In patients treated with DESs, long-term administration of at least one antiplatelet agent must be continued following completion of the mandatory dual antiplatelet regimen. In this review, we summarize the findings available for DESs so far, discuss emerging safety and efficacy data, and look at the future directions for these devices.

Topics: Antineoplastic Agents, Phytogenic; Clinical Trials as Topic; Coronary Restenosis; Endothelium, Vascular; Everolimus; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

Diabetes mellitus has reached epidemic proportions worldwide. Patients with diabetes are at increased risk for acute coronary syndromes, and these syndromes lead to frequent morbidity and cardiovascular mortality. Emerging adjunctive pharmacological strategies coupled with the drug-eluting stent platform have resulted in improved adverse event rates for this high-risk group. This review will concentrate on the historical data associated with acute coronary syndromes in diabetes mellitus, focusing on revascularisation, drug-eluting stents and antiplatelet therapies.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Coronary Disease; Coronary Restenosis; Diabetes Complications; Humans; Paclitaxel; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Sirolimus; Stents; Syndrome

Coronary angiography is often inadequate for estimating the severity of ambiguous left main coronary artery (LMCA) stenoses. Our assessment of these lesions can be improved by the techniques of intravascular ultrasound and fractional flow reserve which provide indices of stenosis severity to enable the prediction of future events and planning of treatment. For patients requiring LMCA revascularization, coronary artery bypass graft (CABG) surgery has been gold standard for decades. However, this technique continues to be limited by factors such as periprocedural mortality, prolonged hospital stay and rehabilitation, and long-term graft patency. LMCA stenosis remains one of the few serious challenges for the interventional cardiologists and, in the bare metal stent era, the long-term results were not sufficient to replace CABG surgery, mainly because of the high restenosis rate. Drug-eluting stents (DES) have dramatically reduced the restenosis rate and early results in small series (approximately 300 patients in total) treated with DES in LMCA have been encouraging, especially for lesions at the ostium and in the left main shaft. Before changes are made in the guidelines for treatment, we must wait for a refinement in the technique and stent design used for bifurcational left main lesion and the results of randomized, specific multicenter studies (SYNTAX trial). It is likely that, for selected patients, LMCA stenosis will be regarded as an indication for PCI.

Topics: Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Blood Vessel Prosthesis Implantation; Coronary Artery Bypass; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Sirolimus; Stents

The percutaneous treatment of patients with obstructive atherosclerotic disease in degenerated coronary saphenous vein bypass grafts still remains one of the great challenges in interventional cardiology. In this review, we discuss the actual evidence-based knowledge for the percutaneous management of this lesion subset, focusing in particular on the devices that are actually considered the "gold standard" for this treatment: bare metal stents and distal protection devices. We also comment on the negative results of the randomized trials regarding the promising polytetrafluoroethylene-covered stent-grafts. We finally offer insights into the currently available evidence for the use of drug-eluting stents in saphenous vein grafts. These devices are potentially the principal promise for the long-term successful sealing of vein graft disease; however, clear and definitive data coming from controlled trials are requested.

Topics: Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Saphenous Vein; Sirolimus; Stents

Drug eluting stent is a new technology aimed to prevent the development of neointimal hyperplasia and restenosis following percutaneous coronary intervention. This review describes the direction for their use at the present time and the future of their utilization with the summary of the principals clinicals trials.

Topics: Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents; Tubulin Modulators

The development of stent has been a major advance in the treatment of obstructive coronary artery disease since the introduction of balloon angioplasty. However, neointimal hyperplasia occurring within the stent leading to in-stent restenosis is a main obstacle in the long-term success of percutaneous coronary intervention (PCI). The recent introduction of drug-eluting stents (DES) contributes a major breakthrough to interventional cardiology. Many large randomized clinical trials using DES have shown a remarkable reduction in angiographic restenosis and target vessel revascularization when compared with bare metal stents. The results of these trials also appear to be supported by evidence from everyday practice and non-controlled clinical trials. However, the expanded applications of DES, especially in treating complex lesions such as left main trunk, bifurcation, saphenous vein graft lesions, or in-stent restenosis, are still under evaluation with ongoing studies. With the availability of different types of DES in the market, the issue of cost should not be a deterrent and DES will eventually be an economically viable option for all patients. The adoption of DES in all percutaneous coronary intervention may become a reality in the near future. In this review article, we summarize the recent development and progress of DES as well as compare and update the results of clinical trials.

Topics: Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug Carriers; Growth Inhibitors; Humans; Hyperplasia; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Thrombosis; Treatment Outcome; Tunica Intima

The number of peripheral procedures is increasing at a rapid pace and in a variety of vessels. This review will discuss current findings in carotid intervention and drug-eluting stents in superficial femoral arteries (SFA).

Topics: Alloys; Carotid Artery Diseases; Coronary Restenosis; Drug-Eluting Stents; Endarterectomy, Carotid; Femoral Artery; Humans; Immunosuppressive Agents; Risk Factors; Sirolimus; Stents; Vascular Patency

Stents have become the technique of choice for percutaneous revascularization, but in-stent restenosis has remained a clinical challenge. This brief article summarizes the incidence, patterns, and proposed mechanisms of restenosis and outlines its contemporary management with specific focus on the diabetic patient. It includes a synopsis of the strategy of drug-eluting stents, which is the most recent and major advance in percutaneous coronary intervention.

Topics: Coated Materials, Biocompatible; Coronary Restenosis; Diabetes Complications; Drug Delivery Systems; Humans; Sirolimus; Stents

The use of intracoronary stents represent a major breakthrough in the armamentarium of interventional cardiology. Stents reduce significantly the incidence of recurrent stenosis (in-stent restenosis) via an improved post-procedure luminal diameter and an abrogation of the constrictive remodeling of the arterial wall. However, stent-related arterial injury results in intense proliferative and inflammatory responses and severe intimal hyperplasia, which, in 20% to 40% of the patients, may end up with clinically significant in-stent restenosis. Efficient prevention of in-stent restenosis has yet to be found. Systemic treatments have failed because they don't take into account the specific physiopathology and, most importantly, the focal nature of in-stent intimal hyperplasia. Hence, local prevention appears to be a straightforward approach to the unsolved issue of in-stent restenosis. In situ beta- or gamma-irradiation (brachytherapy) has received much attention as a curative treatment of in-stent restenosis but is not indicated for prevention. In contrast, drug-releasing stents have been tested in experimental models and have already provided very promising results in randomized clinical trials. Most of clinical studies have been performed with the antiproliferative agents sirolimus and paclitaxel, but other agents are under scrutiny. In addition, important research is carried out, in which the efficacy of antiproliferative genes is investigated. Clearly, drug-releasing stents are on the verge of profoundly modifying our practice of interventional cardiology. However, several questions remain unanswered as regard to the long term efficacy/toxicity and the cost-effectiveness of this new approach.

Topics: Animals; Coronary Restenosis; Drug Delivery Systems; Humans; Hyperplasia; Paclitaxel; Sirolimus; Stents; Tunica Intima

Percutaneous transluminal coronary angioplasty (PTCA) has become the main method of coronary revascularization. However, despite technical advancement, restenosis with incidence rate of 30 to 50% remains a major limitation to the long-term success of PTCA. The introduction of stents has significantly improved capability of interventional cardiology in treatment and prevention of restenosis. Recent experimental studies in animals, clinical studies in humans and multi-center randomized clinical trials with Sirolimus-eluting stents, have demonstrated a significant reduction in vasculoproliferative response with no intimal tissue growth. Moreover, no significant adverse clinical events have been reported at long-term follow-up and first studies that explored the potential of this technology for the treatment of in-stent restenosis demonstrated safety and efficacy. Although the first clinical experiences with drug-eluting stents have produced stunning results, there are a number of theoretical limitations to these devices, including: 1) limitations of drug loading capacity and 2) ability to control drug elution that could result in unfavorable pharmacokinetics. There are also questions about the durability of the polymer coatings (deformation under mechanical stress, gaps between metal and arterial wall, etc). The thickness of some coatings makes them unsuitable for very small vessels. Finally most biodegradable coatings are prone to chronic inflammation. Since only a polymer-coated bare metal stent remains following the drug's release, the potential for long term polymer biocompatibility problems remains a concern. The potential for some drugs to produce radiation-like effects such as "black holes", malapposed and naked struts and wall thinning are potentially the dark side of this technology and may contribute to late thrombosis, aneurysms or delayed restenosis. Long term clinical follow-up is necessary to assess the long term safety of this technology. There is a legitimate question as to whether drug-eluting stents will produce similar results across all patient subsets encountered in "real-life" interventional practice (e.g. long lesions, small diameter vessels, vein grafts, chronic total occlusions, bifurcated and ostial lesions). Cost-benefit issues also need to be addressed, especially because multivessel stenting and multistent usage is likely to increase.

Topics: Angioplasty, Balloon, Coronary; Animals; Cell Division; Clinical Trials as Topic; Coronary Restenosis; Humans; Muscle, Smooth, Vascular; Sirolimus; Stents

Antiproliferative drug-eluting stents represent a miles tone in advances in interventional cardiology. The amount and quality of the scientific evidence now show these new stents to be highly effective in reducing neointimal proliferation, and hence the process of restenosis. Their clinical impact can be expected to become relevant in terms of both increased indications for angioplasty and the extent of stent usage. However, at this time the systematic use of drug-eluting stents for all patients is not considered justified, because of their limited availability, gaps in our knowledge of their safety, and because their unquestioned clinical benefits have been magnified by exaggerated reports of the clinical problem restenosis represents. Currently, the cost of these stents remains high, and the cost/benefit ratio for certain patients is unfavorable. For these reasons selective use of these new stents is considered more reasonable: they should be used only for those patients who will obtain, in absolute terms, the greatest clinical benefit.

Topics: Clinical Trials as Topic; Combined Modality Therapy; Coronary Restenosis; Coronary Stenosis; Costs and Cost Analysis; Drug Delivery Systems; Humans; Paclitaxel; Registries; Sirolimus; Stents

The mechanism of action and pharmacokinetics of sirolimus when used as part of a drug-eluting stent (DES) and the efficacy and cost of using DESs versus bare-metal stents are discussed.. The use of balloon angioplasty with or without coronary artery stenting is limited by the phenomenon of in-stent restenosis (ISR). Until very recently, most efforts to overcome ISR had been ineffective. The search to prevent or reduce the frequency of ISR has led to the recent development of novel coronary artery stents designed to deliver a drug that acts locally. The first DES was approved by FDA in April 2003. This stent releases sirolimus, an agent that inhibits vascular smooth-muscle-cell proliferation. To date, four major clinical trials have demonstrated the sirolimus-eluting stent to be safe and effective in preventing restenosis in de novo coronary artery lesions.. The sirolimus-eluting coronary stent is associated with less ISR than non-drug-containing stents, but further investigation is needed to determine its exact place in the treatment of coronary artery occlusion.

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Cost-Benefit Analysis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Patient Selection; Randomized Controlled Trials as Topic; Safety; Sirolimus; Stents

Topics: Animals; Anti-Inflammatory Agents; Anticoagulants; Coronary Restenosis; Dexamethasone; Heparin; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

To review early clinical experience and future implications of drug-eluting stents (DES) in percutaneous coronary interventions.. Using the search terms sirolimus, paclitaxel, and drug-eluting stents, a literature review was conducted to identify peer-reviewed articles and abstracts in MEDLINE (1966-June 2003). Recent meeting abstracts were also accessed through the American Heart Association and the American College of Cardiology Web sites. Citations from available articles were reviewed for additional references.. Published reviews and studies showing the effects of in-stent restenosis and drug-coated and -eluting stents were evaluated and reviewed.. Current antiplatelet and antithrombotic therapy have proven successful in preventing acute in-stent thrombosis, but not in-stent restenosis. Recently, stents eluted with certain antimitotic agents have demonstrated positive findings in reducing restenosis (eg, sirolimus, paclitaxel-eluting stents) compared with bare-metal stents. However, data regarding long-term benefits and adverse effects are only beginning to accumulate.. While the current clinical efficacy and safety of DES appear promising, further investigations are required to examine long-term efficacy, safety, and cost-effectiveness. Subanalysis of the current data may help to determine the specific patient population that may benefit maximally from DES.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents; Clinical Trials as Topic; Coronary Restenosis; Drug Delivery Systems; Humans; Paclitaxel; Sirolimus; Stents

The inhibitory action of the sirolimus-like agent everolimus on smooth muscle cell proliferation, evidenced in animal models, has triggered the interest in everolimus as stent coating for local inhibition of in-stent restenosis. For preclinical and clinical evaluation of safety and efficacy of an everolimus-eluting stent design, a new stent has recently been introduced by Biosensors International Inc, covered by a resorbable "composite" coating, that contains the immunosuppressive drug within a polyhydroxyacid biodegradable polymer matrix with roughly equal resorption rates. FUTURE I, the feasibility trial of this new stent concept, revealed a 30-day MACE (major adverse cardiac events) rate of 0% as well as a restenosis rate of 0% at 6-month follow-up in a total of 32 patients included. The more sensitive QCA (quantitative computerized analysis) and IVUS (intravascular ultrasound) parameters showed an 88% reduction of in-stent late loss and an 87% reduction of the neointimal volume. Adding a second feasibility trial including diabetics, the multicenter trial FUTURE II confirmed the initial beneficial findings of FUTURE I in a total of 64 patients in a 1 : 2 randomization to a bare metal control stent. Based on these results, the FUTURE program has now been expanded by Guidant with two large-scale multicenter studies, FUTURE III and IV, which evaluate this stent design in a larger patient population. Furthermore, FUTURE IV is addressed to demonstrate the non-inferiority of this stent concept in a head-to-head comparison to an approved drug-eluting stent (DES) concept. In contrast to everolimus, tacrolimus is a well-known potent antiproliferative agent, already used in various therapeutic areas. Preclinical studies on tacrolimus-eluting stents for treatment of native coronary artery lesions demonstrated safety and efficacy of this stent concept with significant reduction of neointimal proliferation within the implanted study stents. However, the clinical trial program of the first tacrolimus-eluting stent system in the treatment of native coronary lesions (PRESENT I, II) and saphenous vein graft lesions (EVIDENT) failed to prove the clinical benefit of the stent systems tested and demonstrated the impact of specific stent designs, especially the drug carrier characteristics, on the patient outcome. The progressive PRESET study, evaluating a directly coated tacrolimus-eluting stent, will provide important insights, that will clarify the potential of tacrolim

Topics: Angioplasty, Balloon, Coronary; Animals; Antibiotics, Antineoplastic; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Everolimus; Feasibility Studies; Humans; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Sirolimus; Stents; Structure-Activity Relationship; Tacrolimus; Treatment Outcome

ABT-578 is a new synthetic analog of rapamycin, designed to inhibit smooth muscle cell proliferation-a key contributor to restenosis-by blocking the function of the mTOR cell cycle regulatory protein. Given these pharmacodynamics, ABT-578 was considered beneficial for intracoronary delivery to arrest the process responsible for neointimal hyperplasia after angioplasty and stenting. Consequently, the ABT-578-eluting ENDEAVOR stent system has been created, representing a potential new alternative for treating patients with coronary heart disease. In order to evaluate safety, feasibility and efficacy of this stent design, the ENDEAVOR clinical program has been started, including three randomized clinical trials. ENDEAVOR I is the first-in-man trial including 100 patients with native de novo coronary lesions. The 4-month follow-up data, recently presented, demonstrated safety and feasibility of this new drug-eluting stent (DES) concept with a 4-month MACE (major adverse cardiac events) rate of 2.0%. In order to evaluate this stent system in a larger patient population as well as more complex lesion subsets, the multicenter study ENDEAVOR II has been started including a total of 1,200 patients. The enrollment of this study was completed in January 2004. The aim of the US multicenter study ENDEAVOR III is a head-to-head comparison of the ENDEAVOR ABT-578-eluting stent system with the already approved sirolimus-eluting Cypher stent in 369 patients. If the results of both pivotal studies ENDEAVOR II and III confirm the efficacy of the ENDEAVOR stent design observed so far, the ENDEAVOR stent will be established as a new and promising contender in the field of DES.

Topics: Administration, Topical; Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Feasibility Studies; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

The success of percutaneous transluminal coronary angioplasty in treatment of acute coronary syndromes has been compromised by the incidence of restenosis. The physical insult of balloon insertion can damage or remove the endothelial monolayer, thereby generating a prothrombotic surface. The resulting inappropriate response to injury can also lead to penetration of inflammatory cells, conversion of the underlying media to a synthetic phenotype, deposition of extracellular matrix, constrictive remodeling, and neointimal hyperplasia. While stent implantation at the time of balloon insertion has offset some of these events, inflammatory responses to the implanted biomaterial (stent) and intimal hyperplasia are still prominent features of the procedure, leading in 20-30% of cases to in-stent restenosis within a year. Systemic delivery of drugs designed to offset in-stent restenosis injury has been largely unsuccessful, which has led to the development of strategies for coating stents with drugs for local delivery. Drug-eluting stents constitute an innovative means of further reducing the incidence of restenosis injury and clinical trials have shown encouraging results. This review focuses on properties of a class of environment-sensitive hydrogels, the N-isopropylacrylamide-based thermoresponsive co-polymers, on their potential roles as stent coatings, on their demonstrated ability to incorporate and release drugs that modify vascular endothelial and smooth muscle cell functions, and on issues that still await clarification, prior to their adoption in a clinical setting.

Topics: Acrylamides; Angioplasty, Balloon; Coronary Restenosis; Drug Delivery Systems; Humans; Hydrogels; Immunosuppressive Agents; Paclitaxel; Polymers; Randomized Controlled Trials as Topic; Sirolimus; Stents; Thrombosis

Sirolimus has been shown to inhibit vascular smooth muscle cell proliferation and migration. Stents coated with a mixture of polymer and active drug achieved near total inhibition of neointimal hyperplasia in patients with de novo coronary lesions. Larger, randomized trials confirmed these initial results to a large extent; late luminal loss was not only reduced by > 70% in patients with type A lesions, but also in complex situations such as diabetic patients, long lesions, and small vessels < 2.5 mm. Registries containing several thousand patients, however, indicate that under realistic conditions the flawless results of the initial studies could not be reproduced in all patient groups.

Topics: Administration, Topical; Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Humans; Polymers; Randomized Controlled Trials as Topic; Sirolimus; Stents

Coronary stent implantation is currently performed in > 80% of percutaneous coronary interventions. Its main late complication is the development of in-stent restenosis (ISR), occurring in 10-80% of lesions treated in daily practice. The classification by Mehran et al. is most commonly used. Current therapeutic options to treat ISR include repeat balloon angioplasty, repeat stenting, cutting balloon angioplasty, directional coronary atherectomy, rotational coronary atherectomy, brachytherapy, and drug-eluting stents (DES). DES have been effective in reducing binary restenosis in de novo lesions in randomized controlled trials. The novel use of DES to treat ISR has been shown to be safe and effective in multiple studies involving sirolimus- and paclitaxel-eluting stents. As DES implantation becomes more widespread, ISR in DES is emerging as a new problem. The use of debulking techniques to treat ISR in DES is to be cautioned against. In this new era, the optimal treatment of this new problem is currently unknown. We await further data to see whether repeat DES implantation may help solve this vexing clinical problem.

Topics: Administration, Topical; Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Humans; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

In-stent restenosis (ISR) remains the "Achilles' heel" of percutaneous stent angioplasty treatment of patients with atherosclerotic disease of the coronary arteries. Recently, drug-eluting stents (DES) have ushered in a revolution in the treatment of these patients, yet, to date, their efficacy and safety have been demonstrated primarily for native de novo coronary lesions. For ISR, intracoronary brachytherapy using beta- or gamma-radiation is considered the standard of care. Nevertheless, DES are used for ISR lesions in clinical practice. This review outlines the few results currently available from small observational studies and larger registries. The designs of two ongoing randomized trials evaluating the sirolimus-eluting and the paclitaxel-eluting stent versus brachytherapy in patients with ISR lesions are also presented. Patients with acute myocardial infarction (AMI) have mostly been investigated in the context of small, uncontrolled studies and registries. The incomplete evidence to date is that implantation of sirolimus-eluting stents in patients with AMI is safe and effective.

Topics: Administration, Topical; Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Brachytherapy; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Vessels; Humans; Myocardial Infarction; Paclitaxel; Sirolimus; Stents; Treatment Outcome

The number of surgical coronary revascularization procedures is static and even declining. Since the introduction of drug eluting stents the question arose whether this will have an impact on the spectrum of surgical coronary revascularization procedures.. Bypass surgery is a routine procedure for the treatment of coronary artery disease with good results. Studies have shown that there is a benefit in favor of surgery compared to interventional cardiologic procedures. DRUG-ELUTING STENTS: In recent studies a new generation of stents, drug-eluting stents, have proven to have a significant better patency rate than common stents. However, to date there are no studies which show a benefit compared to surgery given the same indication for treatment.. Therefore, the question whether drug-eluting stents have an impact on the spectrum of bypass surgery cannot be fully answered at present.

Topics: Administration, Topical; Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Coated Materials, Biocompatible; Coronary Artery Bypass; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Equipment Failure Analysis; Humans; Microscopy, Electron, Scanning; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Convincing end point data demonstrating the anatomic and clinical superiority of stent placement compared with balloon angioplasty together with significant improvement in stenting technique and poststent management have resulted in an explosion in stenting procedures and the emergence of more than 40 stent types with disparate designs and material composition in clinical use. Structural nuances in design, composition, and coating of different stent models, however, have been shown to have a major influence on the risk of stent thrombosis, the degree of vessel wall injury, and subsequent intimal proliferation in the experimental model. There is now substantial amount of evidence to indicate that the same relationship between stent structural characteristics and vessel wall outcome holds true in humans. This article provides an up-to-date overview of the clinical impact of stent construction and design, including the clinical performance of drug-eluting stents.

Topics: Biocompatible Materials; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Humans; Paclitaxel; Prosthesis Design; Sirolimus; Stents

With stenting, restenosis occurs in approximately 25% of patients and the incidence is even higher in patients with diabetes, small coronary vessels and long lesions. The sirolimus-eluting balloon-expandable stent in the treatment of patients with de novo native coronary-artery lesions (SIRIUS) trial, enrolled patients with more challenging conditions, including a higher frequency of diabetes, more complex lesion morphology and longer lesions and showed benefits in all groups. After 240 days, the frequency of stenosis of at least 50% of the luminal diameter was 3.2 and 35.4% in the sirolimus and standard stents groups, respectively. The TAXUS-IV trial was the first large-scale trial on the safety and efficacy of paclitaxel-eluting stents in a broad population of patients and lesions, and established the safety and effectiveness of this agent. After 9 months, there was a mean stenosis of 17% in the paclitaxel group compared to 37% of patients treated with a bare stent. Thus, the local delivery of potent cell cycle inhibitors (sirolimus, paclitaxel) from stents being used for revascularisation dramatically decreases the incidence of restenosis in the populations of patients studied so far and represents a major advancement in the treatment of coronary artery disease.

Topics: Angioplasty, Balloon; Clinical Trials as Topic; Coronary Restenosis; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Cost-Benefit Analysis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Sirolimus; Stents; Treatment Outcome

Based on recent advances, this article aims to review the biological basis for the use of either radiation or drug-eluting stents for the prevention of restenosis, and to elucidate the complementary role that they may play in the future. Vascular restenosis is a multifactorial process primarily driven by the remodeling of the arterial wall, as well as by the hyperproliferation of smooth muscle cells (SMC). These pathophysiological features are the target of therapeutic strategies aimed at inhibiting constrictive remodeling as well as inhibiting SMC proliferation. The success of radiation as well as anti-proliferative drugs such as paclitaxel and sirolimus lies in the primary and/or multifactorial inhibition of cell proliferation. Radiation has the additional feature of preventing constrictive remodeling while sirolimus has the potential property of being anti-inflammatory, which may be a desirable feature. The effects of radiation are not reliant on any uptake and "metabolism" by the target cells, as in the case with drugs, and thus radiation potentially may be more effective as a result of its more-direct action. However, radiation does have some significant drawbacks compared to drug-eluting stents, including a much delayed re-endothelialization resulting in the need for prolonged anti-platelet therapy. Based on recent clinical data, drug-eluting stents have been shown to markedly reduce the likelihood of restenosis, which actually favors this approach for the prevention of restenosis. From a biological perspective, drug-eluting stents and radiation have certain differences, which are reviewed in this article.

Topics: Angioplasty, Balloon, Coronary; Animals; Brachytherapy; Coronary Restenosis; Delayed-Action Preparations; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscle, Smooth, Vascular; Paclitaxel; Sirolimus; Stents

Topics: Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Antineoplastic Agents; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Cost-Benefit Analysis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Polymers; Randomized Controlled Trials as Topic; Sirolimus; Stainless Steel; Stents

The undisputed superiority of stents over conventional balloon angioplasty has resulted in a plethora of stents in clinical use. Recent data, however, have indicated not all stent models are the same. Nuances in stent design and construction have impacted significantly on the immediate and long-term clinical outcome. Among the stainless steel stents, those with multicellular or tubular designs have proven to be superior to coiled or hybrid stent models, and thin-strut stents perform better than thicker-strut stents. Coating stainless steel stents with gold, carbide, phosphorylcholine or heparin do not appear to confer any additional benefit, compared with bare metal stents. In contrast, randomised trials have demonstrated that drug-eluting stents coated with various anti-proliferative drugs, with or without a carrier polymer, afford unparalleled restenosis rates compared with non-drug-eluting stents. Drug-eluting stents, however, are expensive, and their long-term durability and safety remain undefined. Notwithstanding these unresolved issues, it is likely that the majority of percutaneous coronary interventions will involve the use of drug-eluting stents once a more attractive balance between their cost and clinical effects is reached.

Topics: Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Cost-Benefit Analysis; Drug Delivery Systems; Humans; Paclitaxel; Polymers; Prosthesis Design; Randomized Controlled Trials as Topic; Sirolimus; Stainless Steel; Stents

Antiproliferative drug-coated stents are a possible solution for post-angioplasty coronary restenosis. Here we analyze their efficacy, effectiveness and safety, and estimate the economic impact of their use in Spain.. Systematic review (meta-analysis) of the scientific evidence available up to January 2004, and analysis of hospital costs within a 1-year time horizon.. We identified 12 published studies (5 clinical series and 7 RCTs) comparing coated stents (sirolimus or paclitaxel) with conventional stents in patient with de novo single lesions < 30 mm in 2.5-3.5 mm vessels. In nearly all cases the rates of angiographic restenosis and major adverse cardiac events were lower in the coated stent group after 6-12 months. Meta-analysis showed a 69% decrease in revascularization rate (RR=0.31; 95%CI, 0.19-0.51). For every 1000 patients with de novo lesions, the use of a coated stent involved an additional average cost of Euro 818718. The estimated neutral price of a new stent was Euro 1448 at a market price per unit of Euro 2000.. At 12-month follow-up, sirolimus- or paclitaxel-eluting stents were effective and safe in patients with de novo lesions and low or medium risk of restenosis. At current market prices, the widespread use of these stents would involve an increase in health care expenditure for the different sensitivity scenarios we evaluated. More studies are needed to specify the type of patients and lesions likely to obtain the greatest clinical benefit.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Cost-Benefit Analysis; Drug Delivery Systems; Drug Implants; Humans; Paclitaxel; Sirolimus; Spain; Stents

Data accrued to date indicate that stent placement in small vessels (< 3.0 mm reference diameter) suffers from the same disadvantage as other non-stent interventional devices in that the restenosis rate is significantly higher than observed following intervention involving large vessels. Randomized trials comparing systematic bare metal stenting versus conventional balloon angioplasty in the setting of small coronary arteries, however, show that the former therapeutic modality is probably superior to the latter treatment in its acute and mid-term angiographic and clinical results. Balloon angioplasty, even if performed optimally with resultant stent-like luminal outcome, yields a restenosis rate that is at best equivalent to that observed with stent placement. Stent performance is influenced profoundly by stent design and configuration. Tubular and corrugated stents are better than coil or meshwire stent design. Stents with thin struts appear to yield a lower restenosis rate compared with thick-strut stents. Coating the surface of stents with gold, phosphorylcholine or heparin does not appear to confer any additional long-term benefit compared with bare stainless-steel stents. On the other hand, impregnation of stents with anti-proliferative drugs, with or without a carrier polymer, has produced a significantly lower risk of restenosis, without an increase in stent thrombosis rate, compared with uncoated metal stents in multiple randomized trials. However, whether the clinico-anatomic benefits of drug-eluting stents can be sustained for several years and whether there are any long-term deleterious effects from the antiproliferative drug or carrier polymer remains unclear at this stage.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug Delivery Systems; Equipment Design; Humans; Paclitaxel; Sirolimus; Stents

Despite numerous advances in coronary interventional techniques, the frequent occurrence of restenosis continues to plague interventional cardiology. With the widespread use of drug-eluting stents, there is a need to reexamine critically the roles of the various interventional techniques currently available.. Drug-eluting stents have dramatically reduced the rates of restenosis and target vessel revascularization in a wide spectrum of patients with varying lesion morphologies. However, when restenosis does occur, it still tends to be dependent on the same factors that predict restenosis with bare metal stenting. The routine use of drug-eluting stents entails high initial costs to the health care system. Debulking as a means to improve outcomes after angioplasty has not lived up to expectations. Gene therapy is rapidly evolving into a viable means to reduce neointimal proliferation after angioplasty.. Careful patient selection and attention to the procedure of stent deployment optimize the results of angioplasty with drug-eluting stents. Because of cost considerations, drug-eluting stents should be used in patients who are expected to have the greatest absolute benefit. In this context, when judiciously used, conventional balloon angioplasty and bare metal stenting still have a definite role in the management of patients with obstructive coronary artery disease.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug Delivery Systems; Humans; Paclitaxel; Sirolimus; Stents

One of the major advancements in interventional cardiology has been the introduction of drug-eluting stents (DES). By incorporating anti-proliferative agents onto the surface of the stent, neointimal hyperplasia occurring within the stent, which is the main cause of in-stent restenosis (ISR), is markedly reduced. Stents coated with agents, like sirolimus or paclitaxel, when compared to bare metal stents (BMS), had shown remarkable reduction in binary restenosis and target vessel revascularisation (TVR) rates in large randomised clinical trials. The final hurdle of percutaneous coronary intervention (PCI) seems to have been overcome. However, there are still many uncertainties that need to be clarified. The long-term safety of DES remains a major concern; in particular, stent thrombosis and incomplete stent apposition. In the real world, there is a tendency to implant DES in smaller vessels, longer lesions, and complex lesions, as these are high risk for ISR and would yield the greatest benefit. Whether the excellent results of clinical trials of DES can be replicated in these more complex lesions is still unknown and awaits further studies. Although early experience with DES in complex lesions had shown improved results, a higher number of ISR were seen. Finally, the high cost of these devices has precluded their use in all patients undergoing PCI and deliberation among healthcare policy-makers on who should receive DES has centred not only on financial, but also legal and ethical issues. As DES has not completely eliminated ISR and not all patients can afford DES, ISR may survive the initial assault of DES, albeit considerably less in number, for now.

Topics: Coronary Restenosis; Humans; Hyperplasia; Metals; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Thrombosis; Tunica Intima

Recent publications on drug-eluting stents (DES) report a significant reduction in restenosis rates as compared to bare metal stents in patients mostly with single vessel disease. We have recently observed however, late stent thrombosis following CYPHER DES implantation. The patient developed a hypersensitivity reaction around stent struts limited to the polymer with aneurysmal dilatation and extensive inflammation of the arterial wall in the absence of vascular healing. This incidence promotes a cautionary view and perhaps supports the use of DES only in high-risk patients.

Topics: Animals; Coronary Restenosis; Device Approval; Humans; Hypersensitivity; Immunosuppressive Agents; Paclitaxel; Polymers; Sirolimus; Stents; Thrombosis; United States; Wound Healing

The use of drugeluting stents (DES) has tackled the "Achilles' heel" of percutaneous coronary interventions (PCI) like no innovation before: the restenosis following initially successful PCI of de novo stenoses. Today, with DES, the pivotal clinical parameter TVF (target vessel failure) is in the upper single- digit range for "standard" lesions and 16% for long lesions. Numerous studies have assessed the effects of various antiproliferative and antiinflammatory substances, like Sirolimus, Tacrolimus, Everolimus, ABT-578, Biolimus, Paclitaxel, QP2 as well as of other drugs, like Dexamethasone, 17-beta-Estradiol, Batimastat, Actinomycin-D, Methotrexat, Angiopeptin, Tyrosinkinase inhibitors, Vincristin, Mitomycin, Cyclosporin, and also the C-myc antisense technology (Resten-NG, AVI-4126). At the time of this analysis, four DES are CE-certified and commercially available in Europe: The Cypher stent, releasing Sirolimus from a polymer (Cordis, J&J), the Taxus stent, releasing Paclitaxel from a polymer (Boston-Scientific), the V-Flex stent, releasing Paclitaxel without a polymer (Cook) and the Dexamet stent, releasing Dexamethasone from a PC coating (Abbott). Since more DES will be CE-certified soon, an increasing challenge vexes interventional cardiologists and health care providers: Which DES should be chosen for routine patient care?A prerequisite for assessing the efficacy of DES are randomized, controlled trials. Registries, even with strong monitoring, are limited by the known restrictions, comparing data to historical controls. At the time of this analysis, only three drugs had proven their efficacy in 13 randomized studies in 5669 patients: Paclitaxel, Sirolimus and Everolimus, with 3815 patients in Paclitaxel studies, 1748 patients in Sirolimus studies and 106 patients in Everolimus studies. For further analysis, it makes sense to divide the primary endpoints into non-clinical and clinical endpoints. Non-clinical primary endpoints are usually angiographic parameters, like the percentage of DS (diameter stenosis, ASPECT, ELUTES), the instent LLL (late lumen loss, RAVEL, FUTURE-II), the in-stent MLD (minimal lumen diameter, E-SIRIUS, C-SIRIUS) or, like in TAXUS-II, the IVUS-determined percentage of volume obstruction. Clinical primary endpoints were either MACE (major adverse cardiac events, TAXUS-I, FUTUREI), TVF (target vessel failure, DELIVER-I, SIRIUS) or TVR (target vessel revascularization, TAXUS-IV und TAXUS-VI). As ASPECT, ELUTES and DELIVER-I ha

Topics: Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Cost-Benefit Analysis; Diabetes Mellitus; Drug Delivery Systems; Everolimus; Follow-Up Studies; Humans; Immunosuppressive Agents; Paclitaxel; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Stents; Terminology as Topic; Time Factors; Treatment Outcome

The restenosis rate is lower with stent implantation than with balloon angioplasty. Nevertheless, even with the use of stenting, restenosis still occurs in approximately one-third of patients with diabetes, small coronary vessels, and long lesions. The two drugs commonly used in eluting stents are sirolimus and paclitaxel. Systemically administered sirolimus decreased vascular proliferation in animal models. After preliminary trials showing benefit with sirolimus-eluting stents in de novo coronary lesions, the large-scale SIRIUS (Sirolomus-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) trial was undertaken. SIRIUS showed that sirolimus reduced restenosis and target vessel revascularisation, compared to bare stents. These benefits were also apparent in the diabetic, and small- and long vessel subgroups. The RESEARCH (Rapamycin-eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry have established that sirolimus-eluting stents are superior to bare stents in practice. Thus, the benefits of sirolimus-eluting stents over bare stents have been clearly established, and sirolimus can be considered the benchmark eluting agent for the prevention of coronary artery restenosis. Animal studies with paclitaxel-eluting stents, mainly in endothelium denuded normal vessels, have shown that paclitaxel reduces restenosis in the short-term, and that this may be a delay, rather than a prevention of restenosis. In clinical trials, stents eluting the paclitaxel derivative 7-hexanolytaxol, or paclitaxel without a polymer, delay rather than prevent restenosis. Slowing the release of paclitaxel with a polymer base in the TAXUS (Taxol(trade mark) [paclitaxel]-eluting stent) series of clinical trials reduced the revascularisation rate at 12 and 18 months, indicating that polymer-based paclitaxel is effective for longer. The results of the REALITY trial comparing the sirolimus- and paclitaxel-eluting stents in diabetics and other high-risk patients are eagerly awaited.

Topics: Animals; Bridged-Ring Compounds; Clinical Trials as Topic; Coronary Restenosis; Humans; Myocardial Revascularization; Paclitaxel; Sirolimus; Stents

Restenosis is the limiting entity following coronary angioplasty. It is associated with significant morbidity, mortality and cost, and thus represents a major clinical and economical problem. Despite technical improvements, restenosis after conventional balloon angioplasty occurs in 30 - 60% of cases. Coronary stenting was able to reduce the incidence by approximately 30%; nevertheless, some 250,000 patients experience in-stent restenotic lesions/year worldwide. In-stent restenosis has been recognised as very difficult to manage, with a repeat restenosis rate of 50%, regardless of the angioplasty device used. So far, only vascular brachytherapy has convincingly reduced the incidence of repeat in-stent restenosis (by 50%) and thus, has emerged as the gold standard of therapy. The introduction of drug-eluting stents has shown a great deal of promise for the treatment of both de novo and restenotic lesions, with reported restenosis rates of < 10%, and benefit for virtually all patient subsets at a higher risk of restenosis. This review outlines the pathophysiology, epidemiology and predictors of the restenosis process, and places emphasis on the various treatment options for its prevention and therapy.

Topics: Brachytherapy; Coronary Restenosis; Humans; Myocardial Revascularization; Paclitaxel; Randomized Controlled Trials as Topic; Registries; Sirolimus; Stents

Left internal mammary artery to left anterior descending coronary artery bypass grafting integrated with percutaneous coronary angioplasty (hybrid procedure) offers multivessel revascularization with minimal morbidity in high-risk patients. This is caused in part by the avoidance of cardiopulmonary bypass-related morbidity and manipulation of the aorta coupled with minimally invasive techniques. Hybrid revascularization is currently reserved for particularly high-risk patients or those with favorable anatomic variants however, largely because of the emergence of off-pump coronary artery bypass grafting, which permits more complete multivessel revascularization, with low morbidity in high-risk groups. The wider introduction of hybrid revascularization is limited chiefly by the high number of repeat interventions compared with off-pump coronary artery bypass grafting, which occurs because of the target vessel failure rate of percutaneous coronary intervention. Other demerits are the costs and logistic problems associated with performing two procedures with differing periprocedural management protocols. Recently, drug-eluting stents have reduced the need for repeat intervention after percutaneous coronary intervention, and this has raised the possibility that the results of hybrid revascularization may now equal or even better those of off-pump coronary artery bypass grafting. Although undoubtedly effective at reducing in-stent restenosis, drug-eluting stents will not address the issues of incomplete revascularization or the logistic problems associated with hybrid. Uncertainty regarding the long-term effectiveness of drug-eluting stents in many patients, as well as their high cost when compared with those of off-pump coronary artery bypass grafting surgery, also militates against the wider introduction of hybrid revascularization.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cohort Studies; Combined Modality Therapy; Coronary Artery Bypass, Off-Pump; Coronary Restenosis; Disease-Free Survival; Drug Implants; Evaluation Studies as Topic; Female; Hospital Mortality; Humans; Internal Mammary-Coronary Artery Anastomosis; Length of Stay; Male; Middle Aged; Minimally Invasive Surgical Procedures; Multicenter Studies as Topic; Myocardial Ischemia; Paclitaxel; Prospective Studies; Randomized Controlled Trials as Topic; Reoperation; Retrospective Studies; Sirolimus; Stents; Treatment Outcome

Drug-eluting stents have been developed to prevent in-stent restenosis following percutaneous coronary revascularization. In a number of randomized trials, polymer-coated sirolimus- and paclitaxel-eluting stents have been proven to markedly reduce the incidence of angiographic restenosis and repeat revascularization when compared to bare metal stents. Effectiveness of sirolimus-eluting stents in the prevention of restenosis has been confirmed in many subsets of patients and lesions not included in randomized trials, such as in-stent restenosis, chronic total occlusion, acute myocardial infarction, and others. Very promising data in the real world are emerging for utilization of paclitaxel-eluting stents as well. Other drug-eluting stents gave less brilliant results or even true failures, whilst a number of new drugs and stent platforms are under clinical or preclinical evaluation. In this review we describe the main clinical trials on drug-eluting stents, and the most recent informations derived from observational studies and registries. Moreover, preliminary results on new drug-eluting stents are summarized.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coronary Disease; Coronary Restenosis; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Paclitaxel; Polymers; Randomized Controlled Trials as Topic; Sirolimus; Stents

Percutaneous treatment of coronary bifurcation lesions remained challenging in the stent era, with restenosis rates greater than 30% and no advantage from the routine use of kissing stents. Drug eluting stents (DES) have dramatically reduced the restenosis rates (RR) in the main vessel, but with conventional T-stenting double digits figures are still reported for the side-branch because of poor ostial coverage. The techniques of kissing stenting able to provide full lesion coverage (Culotte, V-stenting, Crush) have the potential to improve these results but the development of dedicated DES is probably needed to obtain consistently high procedural and long-term success.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coronary Restenosis; Coronary Stenosis; Drug Therapy, Combination; Equipment Design; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Saphenous vein graft (SVG) disease has been an obstinate problem facing the cardiologist since the early days of coronary artery bypass grafting (CABG) surgery. SVG disease follows temporally distinct phases of thrombosis, intimal hyperplasia and progressive atherosclerosis leading to recurrent ischemia which can be treated with repeat operation or percutaneous revascularization. However, repeat operation is associated with high mortality and morbidity. Also, percutaneous treatment of SVG disease is complicated by a high rate of procedural and long term complications due to the interrelated phenomena of distal embolization, slow flow or no reflow, periprocedure myocardial infarction, and subsequent restenosis. Long-term patency is poor in this patient population regardless of the treatment modality. Many pharmaceutical and device based approaches have been tested to avert these complications, but few, such as the use of distal protection devices, have shown benefit. The novel drug-eluting stents show promise in reducing the occurrence of restenosis and solving one of the problems associated with the percutaneous treatment of SVG disease. The pathogenesis and therapeutic options for SVG disease is reviewed in this article.

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Coronary Restenosis; Drug Therapy, Combination; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Saphenous Vein; Sirolimus; Stents; Treatment Outcome

In multiple clinical trials, patients who received drug-eluting stents instead of plain stents during percutaneous coronary interventions had rates of restenosis that were lower by roughly one half to three fourths, depending on how restenosis was defined and on the population studied. These stents will likely be used more and more as their indications evolve.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug Carriers; Drug Delivery Systems; Humans; Leukocytes; Myocytes, Smooth Muscle; Paclitaxel; Sirolimus; Stents

Coronary artery disease is the largest killer of men and women in the United States and costs the health care system billions of dollars annually. Several advances in both mechanical and pharmacologic treatment of coronary artery disease have occurred in recent decades. Mechanically, percutaneous coronary intervention is commonly used to treat coronary atherosclerosis. This approach has dramatically reduced both morbidity and mortality for patients with different levels of severity of coronary artery disease. However, percutaneous coronary intervention is limited by restenosis, which is an increase in growth of the intimal layer of the vessel wall. Despite the introduction of intracoronary stents and the addition of systemic pharmacotherapy, restenosis still affects a significant number of patients. The new technology of drug-eluting stents combines mechanical and pharmacologic approaches to prevent restenosis. Various types of these stents exist in different stages of development; several have been shown to prevent or reduce intimal growth after stent deployment. An understanding of how this combined mechanical and pharmacologic approach reduces restenosis requires consideration of complex issues in pathophysiology and pharmacology.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents; Brachytherapy; Clinical Trials as Topic; Coronary Disease; Coronary Restenosis; Female; Humans; Male; Paclitaxel; Sirolimus; Stents

Topics: Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Antifungal Agents; Atherectomy, Coronary; Clinical Trials as Topic; Coronary Restenosis; Humans; Immunosuppressive Agents; Multicenter Studies as Topic; Paclitaxel; Placebos; Randomized Controlled Trials as Topic; Sirolimus; Stents; Time Factors; Treatment Outcome

Drug-eluting stenting is part of the evolution of interventional cardiology that started with Gruentzig's introduction of balloon angioplasty in 1977. Numerous advances in interventional cardiology technique have occurred since that time, and drug-eluting stents hold promise for reducing the restenosis rate but as yet have not been shown to influence survival or freedom from myocardial infarction. The ability of stents to influence these hard end points will be tested against the most difficult patient subset for interventional cardiology: persons with diabetes mellitus and multivessel disease. As more data are accumulated, prudent selective use of drug-eluting stenting seems most appropriate.

Topics: Angioplasty, Balloon, Coronary; Anti-Infective Agents; Brachytherapy; Coronary Angiography; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Follow-Up Studies; Humans; Immunosuppressive Agents; Meta-Analysis as Topic; Multicenter Studies as Topic; Paclitaxel; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Stents; Time Factors

Coronary revascularization procedures are associated with less favourable outcomes in diabetic patients as compared to non-diabetic individuals. Especially, percutaneous coronary angioplasty (PTCA) is associated with a high level of restenosis and recurrent cardiac morbidity and mortality. In diabetic patients, PTCA should ideally be combined with stents. Bare-metal stents reduce by almost half the risk of restenosis, but this favourable effect decreases with the vessel calibre, a common finding in diabetic patients. Drug-eluting stents containing pharmacological agents that can reduce the risk of restenosis (sirolimus, paclitaxel) provide better angiographic results, including in small coronary arteries, and this effect has been shown to be accompanied by significant reduction of both morbidity and mortality. Such preliminary results obtained in the general population (including around 20% of diabetic subjects) deserve further confirmation in a large clinical trial specifically devoted to diabetic patients. Drug-eluting stents may represent a major advance in the management of diabetic patients with coronary heart disease in the near future.

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Diabetes Complications; Drug Delivery Systems; Humans; Paclitaxel; Platelet Aggregation Inhibitors; Sirolimus; Stents

Less than a year after their release, drug-eluting stents are being used in more than 70% of patients who undergo percutaneous intervention for obstructive coronary disease in the United States. This unprecedented quick adoption was fueled by results of several randomized trials that demonstrated a profound reduction in restenosis rates compared with bare-metal stents. Subset analysis of the drug-eluting stent trials shows a strong restenosis reduction rate across a wide range of patient characteristics; however, these broad beneficial effects are based on randomized subjects who may not represent the actual population currently being treated with coronary stents. This review presents an analysis of the available data on the approved drug-eluting stents, including patient subsets that may or may not benefit; potential stent-specific complications; and a discussion of costs, risks, and cost-effectiveness.

Topics: Coronary Restenosis; Cost-Benefit Analysis; Diffusion of Innovation; Drug Delivery Systems; Evidence-Based Medicine; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Sirolimus; Stents

Topics: Angiogenesis Inhibitors; Brachytherapy; Coronary Restenosis; Drug Implants; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

Restenosis is the most important long-term limitation of stent implantation for coronary artery disease, occurring in 15-60% of patients. In-stent restenosis, a refractory coronary lesion resulting from neointimal hyperplasia, challenges both vascular biologist and interventional cardiologist. Various drugs and devices have been used tried to overcome restenosis but are not particularly successful. Over 1500000 percutaneous coronary interventions are done annually. Restenosis is not only important clinically but also for its impact on health-care costs.. Growth and migration of vascular smooth-muscle cells result in neointimal proliferation after vascular injury and are the key mechanism of in-stent restenosis. The rationale of the most recent approaches to restenosis (eg, brachytherapy and immunosuppressive agents) arises from the similarity between tumour-cell growth and the benign tissue proliferation which characterises intimal hyperplasia. Several immunosuppressants have been tested for their potential to inhibit restenosis, with the novel strategy of administering the drug via a coated stent platform. Local drug delivery achieves higher tissue concentrations of drug without systemic effects, at a precise site and time. The first multicentre trial with stents coated with sirolimus was by Marie-Claude Morice and colleagues (N Engl J Med 2002; 346: 1773-80). In a trial of 238 patients, restenosis of 50% or more at 6 months was 0% and 27% with sirolimus or normal stents (p<0.001), respectively, after percutaneous revascularisation. Muzaffer Degertekin and colleagues (Circulation 2002; 106: 1610-13) present data on 2-year follow-up of 15 patients who had been implanted with the sirolimus stent in another study, and confirm persistent inhibition of restenosis and an absence of unexpected adverse events. WHERE NEXT? Local application of antiproliferative agents is a promising technique and research is developing. Other agents with potential benefits (eg, statins, local gene-therapy, adenovirus-mediated arterial gene-transfer, L-arginine, abciximab, angiopeptin, recombinant pegylated hirudin, and hiloprost) as well as improvements in polymer technology (biodegradable smart polymers, coatings for multiple-drug release) are under evaluation. The clinical impact of the elimination of restenosis may influence the approach to coronary artery disease, the future of cardiac surgery, and health-care economics in cardiology.

Topics: Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Coronary Restenosis; Humans; Sirolimus

The cellular action of rapamycin (sirolimus), a natural fermentation product produced by Streptomyces hygroscopicus, is mediated by binding to the FK506 binding protein. By inhibiting a kinase known as the target of rapamycin, it restricts the proliferation of smooth-muscle cells by blocking cell-cycle progression at the G1/S transition. The finding that rapamycin possesses both anti-proliferative and antimigratory activity suggests that it could contribute to the control of arterial re-narrowing after percutaneous intervention and control the vascular manifestations of chronic rejection in transplanted hearts. The first clinical trials of implantation of rapamycin- coated stents in obstructive coronary artery lesions have been reported and, in selected patient groups, it appears that the restenosis process has been abolished. Studies are underway to establish the benefits of rapamycin-coated stents in day-to-day interventional practice, including small vessels, long lesions and patients with multivessel disease. With the addition of novel antiplatelet agents and delivery systems, it is possible that the two major limitations of percutaneous coronary intervention - restenosis and stent thrombosis - will be overcome. Cardiac graft loss due to intimal hyperplasia and accelerated atherosclerosis remains the major limitation to long-term survival following cardiac transplantation. Animal studies of rapamycin have suggested that this process can be reduced or abolished. Human studies of the efficacy of rapamycin in preventing both acute rejection and allograft arterial disease are in progress. Concerns regarding toxicity, carcinogenicity, delayed healing and endothelialization remain. As with any new agent or technology, we must remain vigilant to late adverse side-effects.

Topics: Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Graft Rejection; Humans; Immunosuppressive Agents; Sirolimus; Stents; Transplantation Immunology

Many different approaches have been evaluated to prevent restenosis in stents after vascular implantation. Currently, drug-eluting stents are extremely promising in suppressing neointimal hyperplasia. Various animal studies and randomized trials in humans have shown excellent results in terms of safety and efficacy during intermediate-term follow-up. This article will give an overview of experimental and clinical data of the different agents in published and ongoing trials.

Topics: Angiogenesis Inhibitors; Anti-Inflammatory Agents; Arterial Occlusive Diseases; Coronary Restenosis; Dexamethasone; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Prosthesis Design; Recurrence; Sirolimus; Stents; Vascular Patency

Topics: Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Humans; ortho-Aminobenzoates; Paclitaxel; Probucol; Radiotherapy; Sirolimus; Stents; Trapidil

For interventional cardiologists restenosis has represented the main limit for the successful long-term treatment of coronary artery disease. The past 2 years witnessed the extraordinary results of drug-eluting stents (DES), putting this technique at the center stage. The safety and efficacy of sirolimus and paclitaxel-eluting stents have been proved in large prospective, multicenter, randomized trials (RAVEL, SIRIUS, TAXUS II). It is possible that the introduction of DES will lead to substantial changes in the therapeutic and/or the economic strategies of the treatment of ischemic coronary artery disease (increase in the complexity of patients treated, reduction in surgical indications, growing costs). Realizing the potential value of this technology will require the successful management of more complex coronary situations (for lesions and patients characteristics). Many extreme situations are still unexplored, although for some of them studies are currently in progress or already being planned.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Costs and Cost Analysis; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents

Interventional cardiology has evolved tremendously over the past two years with the advent of drug-eluting stents. The RAVEL trial was the first randomized study conducted with sirolimus-eluting stents in a selected population of patients in whom a 0% rate of binary restenosis was achieved. The objective of the SIRIUS trial conducted in a more complex patient population was to test the efficacy of the sirolimus-eluting stent in high-risk settings such as coronary bifurcation lesions.

Topics: Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Sirolimus; Stents; Time Factors

The treatment of in-stent restenosis (ISR) remains one of the major therapeutic challenge for the interventional cardiologist. All percutaneous mechanical approaches have shown disappointing results and the recurrence of ISR was reported to be unacceptably high. Currently, the only proven effective therapy available for the treatment of ISR, at least for the most complex lesions, is vascular brachytherapy. However, this therapy is limited by potential side effects and logistic requirements. The introduction of drug-eluting stents, that carry and release antiproliferative agents, have demonstrated to virtually eliminate ISR in de novo lesions. In the light of this promising results for de novo lesions, sirolimus-eluting stents (SES) were recently used for the treatment of ISR in 2 pilot studies. In Sao Paulo, 25 patients with ISR treated with SES (1.4 stent per lesion) presented 4% ISR and no clinical events at 1 year. In Rotterdam, 16 patients with severe ISR were treated with 26 SES. Intravascular ultrasound evaluation demonstrated successful inhibition of neointimal hyperplasia with 1.1% volume obstruction of the stent, which is similar to the Sao Paulo series (0.8%). At 9 months clinical follow-up, 3 patients had experienced 4 major adverse cardiac events (2 deaths and 1 acute myocardial infarction necessitating repeat target vessel angioplasty). With the results presently available, SES implantation can be considered safe and potentially efficacious in the treatment of ISR. However, multicenter, long-term randomized studies are warranted in order to evaluate this new treatment concept.

Topics: Coronary Restenosis; Drug Delivery Systems; Equipment Design; Humans; Immunosuppressive Agents; Registries; Sirolimus; Stents

Drug-eluting stents (DES) promise to change the landscape of interventional cardiology, overcoming restenosis that is the major limitation of percutaneous coronary interventions. Intravascular ultrasound (IVUS) examination has been at the centre of our efforts to understand the mechanisms and define different treatment strategies during coronary interventions. IVUS interrogation and 3-dimensional IVUS measurements have been used to better define the mechanisms of benefit and potential drawbacks of DES. The findings of these studies are summarized in this article and the potential importance of IVUS in the era of DES is discussed. Evidence of neointimal hyperplasia (IH) suppression and assessment of any edge effect or vessel remodeling after implantation of DES has been evaluated by IVUS. The overall clinical importance of IVUS in the new era will depend on the amount and the clinical significance of any unsolved questions we will face and on its ability to provide answers to the evolving questions.

Topics: Clinical Trials as Topic; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents; Ultrasonography, Interventional

Although coronary stenting has improved the results of coronary interventions compared to coronary angioplasty alone, in-stent restenosis remains a significant limitation of this procedure. Drug-eluting stents with or without glycoprotein IIb/IIIa inhibitor therapy represent an additional advance in the evolution of this strategy.. We review the currently available trials comparing studies of non-drug-eluting and drug-eluting stents using sirolimus and paclitaxel agents and their derivatives.. Ten studies are available that compare drug-eluting to traditional non-drug-eluting stents. A variety of antiplatelet regimes have been used. The majority of these studies are in the process of being published. No head-to-head studies comparing different drug-eluting stents are available.. Drug-eluting stents using sirolimus and paclitaxel in combination with enhanced antiplatelet strategies represent an important advantage over non-drug-eluting stents for the reduction of in-stent restenosis. The rate at which drug-eluting stents are adapted into widespread practice depends heavily on whether they are safe, efficacious, and cost-effective in various clinical settings.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents; Clinical Trials as Topic; Combined Modality Therapy; Coronary Restenosis; Diabetic Angiopathies; Humans; Paclitaxel; Platelet Glycoprotein GPIIb-IIIa Complex; Sirolimus; Stents

Topics: Angioplasty, Balloon, Coronary; Cardiology; Coronary Restenosis; Drug Delivery Systems; Humans; Paclitaxel; Sirolimus; Stents

In this article, the authors intend to provide an update on clinical trials of pharmacologic prevention of restenosis after percutaneous coronary interventions, placed in the perspective of the use of orally administered therapy for the prevention of atherosclerosis progression and clinical events.. AGI-1067, the mono-succinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed v-protectants. It has strong antioxidant properties equipotent to those of probucol and antiinflammatory properties. It inhibits gene expression of VCAM-1 and MCP-1 and has been effective at preventing atherosclerosis in all tested animal models including the non-human primate. In the Canadian Antioxidant Restenosis Trial (CART) 1, AGI-1067 and probucol improved lumen dimensions at the site of percutaneous coronary intervention. AGI-1067 also improved luminal dimensions of non-intervened coronary reference segments in the Canadian Antioxidant Restenosis Trial, which suggests a direct antiatherosclerosis effect. Probucol reduced post-percutaneous coronary intervention restenosis and progression of carotid atherosclerosis in other clinical trials. Although statins reduce atherosclerotic events, they do not appear to have a significant effect on restenosis. The failure of folate therapy to protect against restenosis in the Folate After Coronary Intervention Trial (FACIT) occurred despite significant reductions in homocysteine levels.. Prevention of both post-percutaneous coronary intervention restenosis and atherosclerosis progression with a pharmacologic agent such as AGI-1067 may be an attractive treatment paradigm. Two important trials that test the antioxidant/antiinflammatory hypothesis are ongoing with AGI-1067: the Canadian Atherosclerosis and Restenosis Trial 2, which assesses its value for the reduction of both atherosclerosis progression and post-percutaneous coronary interventions restenosis, and the Aggressive Reduction of Inflammation Stops Events (ARISE) trial which is evaluating its effects on cardiovascular events.

Topics: Anti-Inflammatory Agents; Anticholesteremic Agents; Antioxidants; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; ortho-Aminobenzoates; Oxidative Stress; Probucol; Sirolimus; Vitamins

Drug-eluting stents are revolutionizing interventional cardiology. Sirolimus-eluting stents are in widespread clinical use, associated with well-documented remarkably low restenosis rates, and a number of other agents appear promising in clinical trials. These human studies have been preceded by numerous animal studies, foremost among them the pig coronary model of in-stent restenosis (ISR). The histologic response to porcine coronary stenting was described over a decade ago. Porcine stenting studies now provide examinations not only of histology, but also mechanisms of action, toxicity, and biocompatibility. This review therefore examines the current status of this porcine coronary model of ISR. Contemporary methods of pig coronary stenting are discussed. The morphometric, cellular, and molecular analyses of the responses to stent injury are then described. Finally, recent pig coronary drug-eluting stent studies are examined, with a discussion of their advantages, limitations, and possible future modifications.

Topics: Animals; Coronary Restenosis; Disease Models, Animal; Drug Delivery Systems; Immunosuppressive Agents; Sirolimus; Stents; Swine

Since the advent of percutaneous coronary intervention (PCI) for stenosing coronary disease, restenosis has remained a clinical problem. Despite the emergence and evolution of coronary stents, the rate of restenosis following PCI is still 10-20%, and above 50% in high risk subgroups. With increased understanding of the pathophysiology of this process, a number of potential therapeutic targets have been identified, allowing the development of novel therapies against restenosis, which can now be delivered locally using stent platforms. Some of the reported clinical trial data utilizing drug-eluting stents (DES) have produced such profound reductions in clinical and angiographic restenosis that we have been tempted to believe we are on the brink of eradicating this process completely. As the initial excitement subsides, however, there is a need to decide whether these tools will remain effective in real-world interventional practice. In this article we review the pathophysiology of the restenotic process, and the biological targets of the DES therapies currently available in clinical practice. We attempt to define clinical target populations for DES therapy, and assess the impact on outcomes thus far. We consider the advantages that newly emergent stent coatings might offer, and whether targeting specific patient subgroups with unique antiproliferative agents may provide the best chance of limiting restenosis in high risk subgroups. Finally, we consider future strategies to prevent restenosis, with a movement away from the antiproliferative approach, and toward accelerating endothelialization.

Topics: Antibiotics, Antineoplastic; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Forecasting; Humans; Immunosuppressive Agents; Paclitaxel; Risk Factors; Sirolimus; Stents

Transcatheter endovascular therapy for peripheral atherosclerotic disease has become more popular. In general, good results have been reported in focal aortoiliac disease. However, the long-term patency of angioplasty in longer, more distal lesions has been less satisfactory. Stenting has not been shown to improve long-term patency compared to angioplasty alone. Drug-eluting stents have shown promise in preventing coronary restenosis, and preliminary results in peripheral arterial disease are encouraging. This review article will discuss the current status of endovascular therapy of aortoiliac and femoropopliteal atherosclerotic disease, the theoretic and experimental basis for the use of drug-eluting stents, and the preliminary results in human studies.

Topics: Angiogenesis Inhibitors; Anti-Inflammatory Agents; Arterial Occlusive Diseases; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Peripheral Vascular Diseases; Prosthesis Design; Recurrence; Sirolimus; Stents; Vascular Patency

Restenosis is the process of luminal narrowing in an atherosclerotic artery after an intra-arterial intervention such as balloon angioplasty and stenting. It is believed that this process is mainly characterized by migration and proliferation of smooth muscle cells and extracellular matrix accumulation. However, there is now increasing evidence for a role of inflammation in the development of restenosis. The underlying molecular mechanisms of restenosis are, in fact, most probably regulated by inflammatory mediators, such as cytokines. Understanding the molecular mechanisms in restenosis is crucial for the development of a suitable therapy for this disease. Recently, the use of immunosuppressives in drug-eluting stents has provided very promising results in the treatment of restenosis. In this review, we will describe the molecular mechanisms involved in restenosis with a focus on the role of inflammation and the use of immunosuppressive therapy.

Topics: Coronary Restenosis; Cyclosporine; Humans; Immunosuppressive Agents; Inflammation; Inflammation Mediators; Sirolimus; Tacrolimus

The long-term success of percutaneous coronary intervention in the treatment of coronary artery disease is hampered by the occurrence of restenosis, which often necessitates repeat hospitalisations or coronary interventions. The advent of drug-eluting stents, particularly those coated with sirolimus and paclitaxel, may be the breakthrough in the battle against restenosis that interventional cardiologists have been waiting for, and we review the currently available evidence for this. Despite the growing enthusiasm, we should not forget that this new technology is still in its relative infancy, and there remain many unanswered questions, particularly about the long-term effect of using these stents.

Topics: Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Restenosis; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents; Atherectomy, Coronary; Brachytherapy; Coronary Artery Disease; Coronary Restenosis; Humans; Paclitaxel; Sirolimus; Stents; Ultrasonography, Interventional

Nowadays stent placement has replaced balloon angioplasty as the most commonly performed percutaneous coronary interventional procedure, mainly because of its better acute and chronic outcome. As a result, in-stent restenosis (ISR) has become a widespread problem. The incidence of ISR varies from 10% to 50% and depends on the absence or presence of several risk factors, such as small vessel size, longer lesions, and diabetes. Intravascular ultrasound studies have demonstrated that ISR is mainly caused by neointimal proliferation; consequently, this pathologic process has become the target of many preventive and therapeutic approaches. This article provides an overview of such management strategies, highlighting the rather disappointing experiences with mechanical and systemic drug therapies; the relative merits and disadvantages of intracoronary radiation; and the exciting yet realistic promise, embodied by the recent advancements in drug-eluting stent technology, of potentially eradicating ISR in the near future.

Topics: Angioplasty, Balloon, Coronary; Animals; Brachytherapy; Cell Cycle; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Gene Transfer Techniques; Humans; Paclitaxel; Sirolimus; Stents

Stent implantation represents the most commonly performed percutaneous coronary intervention nowadays. However, instent restenosis due to exaggerated neointimal hyperplasia remains a problem to overcome. Neointimal hyperplasia is a vascular response to stent injury; it mainly consists of smooth muscle cells proliferation. The underlying molecular mechanisms of restenosis were explained in this review article. Recently, drug-eluting stent has been proposed as a potential method to prevent instent restenosis. Animal studies have confirmed safety and efficacy of sirolimus-eluting stent implantation in vivo. The FIM trial, which was the first clinical study on sirolimus-eluting stent in de novo lesions, has shown an astonishing 0% restenosis rate. The RAVEL trial was the first prospective, double-blind, multi-center trial that randomized 238 patients at 19 institutions with de novo lesions into sirolimus-eluting versus bare Bx velocity stent. Six-month binary restenosis rate in the sirolimus-group was again 0% compared to 26.6% in the control group. Angiographic late loss and major cardiac event were also significantly lower in the sirolimus-group. The SIRIUS trial is an ongoing study conducted in 53 US centers that randomized 1100 patients with de novo lesion into sirolimus-eluting and bare stents. Preliminary results also showed a significant reduction in binary restenosis, late loss and repeat revascularization rates. Apart from de novo lesions, early experience of sirolimus-eluting stent implantation for instent restenosis in non-randomized study was also promising, achieving a single-digit repeat restenosis rate. As compare with standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis and associated clinical events.

Topics: Angioplasty, Balloon, Coronary; Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Double-Blind Method; Humans; Immunosuppressive Agents; Multicenter Studies as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Registries; Risk Factors; Sirolimus; Stents; Swine

Drug-eluting stents represent the third revolution in the field of Interventional Cardiology following balloon angioplasty (PTCA) and the implantation of metal stents. The main limitation of percutaneous coronary intervention (PCI) is restenosis. The introduction of drug eluting stents able to release antiproliferative compounds led to the evaluation of several antiproliferative drugs in order to reduce restenosis. Rapamycin (Sirolimus) has been demonstrated to inhibit smooth muscle cell (SMC) proliferation and migration in vitro and to reduce in vivo neointima formation with blockage of the cell cycle progression at the G1-S transition. In a pilot study, recently confirmed by a randomized trial, rapamycin drug-eluting stents have been reported to eliminate restenosis after stent implantation. Promising data also come from the use of paclitaxel drug-eluting stents. Paclitaxel (Taxol) is a microtubule-stabilizing agent with potent antiproliferative activity. Even if drug-eluting stents represent one of the most promising fields in Interventional Cardiology today before being sure of their real potential it is necessary to wait for results from several ongoing clinical studies, their usage in real-world lesions and extended follow-up to 5 years.

Topics: Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Follow-Up Studies; Forecasting; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Paclitaxel; Pilot Projects; Randomized Controlled Trials as Topic; Sirolimus; Stents; Time Factors

Percutaneous coronary interventions (PCI) have surpassed coronary artery bypass grafting as the most common means for treating coronary artery disease, because of materials improvement, the use of stent and pharmacotherapy. However, despite the variety of mechanical techniques such as dilatation, debulking or conventional stent implantation, the incidence of restenosis on short and mid-term follow-up is still representing an important limitation to PCI. Restenosis is mainly due to elastic recoil, negative vessel remodelling and neointimal proliferation, as a response to vessel injury induced by angioplasty devices. The use of conventional stents has provided an efficient method to avoid elastic recoil and negative vessel remodelling, thus partially reducing restenosis as compared to conventional balloon dilatation. However, neointimal proliferation (biological vessel response to injury caused by stent implantation) is not affected by stenting technique. Thus, the extensive use of coronary stent, even in complex lesions, have produced again a "new" disease: the in-stent restenosis especially in some patients' subset (diabetics) or in some lesion subset (bifurcations, long lesions, small vessels, total occlusions, diffuse disease). Therefore, the main target of today's interventional cardiologists is to resolve this problem. The combination between mechanical control of elastic recoil and negative remodelling (stent) and the control of neointimal proliferation - biological response to vessel injury - (antiproliferative drugs) is the emerging approach against restenosis. This emerging approach consists in using the stent as drug carrier to the target site. Local delivery of antiproliferative or immunosuppressive agents using a drug-coated stent is supposed to inhibit in stent restenosis. The first antiproliferative agents being used successfully in clinical trials are sirolimus and paclitaxel and, so far, the data available of these trials demonstrated a marked reduction of restenosis using sirolimus- and paclitaxel-coated stents as compared to conventional stents. However, many questions are still to be answered and several other clinical trials with drug-eluting stents are ongoing, evaluating safety and efficacy of sirolimus and paclitaxel in a larger number of patients and in different subset of coronary lesions type and morphology. Based on the very impressive results available at the present time, we can expect, in the very near future, remarkable chang

Topics: Angiogenesis Inhibitors; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Clinical Trials as Topic; Coronary Restenosis; Humans; Immunosuppressive Agents; Multicenter Studies as Topic; Paclitaxel; Pharmaceutical Preparations; Prospective Studies; Randomized Controlled Trials as Topic; Sirolimus; Stents; Time Factors

Drug-eluting stents (DES) have entered the arena and are about to changed the landscape of Interventional Cardiology. Today, the number of agents under preclinical and clinical investigation has increased considerably, including drugs such as Paclitaxel, Sirolimus, Tacrolimus, Everolimus, Dexamethasone, etc. Several studies have recently been published or are still ongoing evaluating different stent designs with respect to their safety and efficacy in treatment of coronary lesions. The SCORE trial (Paclitaxel) revealed a significant reduction in restenosis at follow-up (FU) in the drug-eluting stent group (6.4% vs 36.9% control group), attributable to decreased intimal proliferation. However, stentthromboses and myocardial infarctions, due to both stent design and high drug dosages, were observed causing a MACE rate of 10.2% in the DES group. Confirming the beneficial reduction of stent renarrowing using a local drug-eluting device, the rate of restenosis in the TAXUS-I trial (Paclitaxel) was 0% at follow-up in patients with DES vs 10% in patients with bare stents. Differences in MACE were not observed, which underlined the potential impact of an optimal stent design. First clinical experiences with a Sirolimus-coated stent (FIM trial) demonstrated again a profound inhibition of neointimal ingrowth at 4-month follow-up. The RAVEL trial, the first multicenter trial evaluating the Sirolimus stent and the largest DES study published so far, confirmed the FIM findings with a rate of restenosis in the DES group of 0% at 6 month FU. At 12 month FU, the beneficial impact on neointimal growth inhibition was persistent. The pivotal study SIRIUS is addressed to evaluate this stent design more extensively. However, given all the results being available today, local application of anti-proliferative agents delivered by coronary stents is one of the most promising techniques in treatment of coronary lesions. Nevertheless, we need more trials and an agreement of definitions in order to evaluate this treatment concept and eliminate unwanted side-effects.

Topics: Angiogenesis Inhibitors; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Follow-Up Studies; Humans; Immunosuppressive Agents; Multicenter Studies as Topic; Paclitaxel; Pharmaceutical Preparations; Randomized Controlled Trials as Topic; Safety; Sirolimus; Stents; Time Factors

The need for repeat interventions after initially successful PTCA due to restenosis has been called the "Archilles heel" of a percutaneous revascularization procedure. The incidence of restenosis varies between 20-50 % depending on the stent material, the presence of risk factors, and the location of vascular disease. Some risk factors such as diabetes have been clearly identified, others are currently debated. After years of failures trying to reduces restenosis rates, locally administered antiproliferative means have been shown to successfully inhibit excessive cell growth in response to PTCA. Local radiotherapy of in-stent restenosis results in a reduction of recurrent stenosis versus a conventional PTCA procedure. However, long-term evaluation indicated that restenosis may only be delayed with radiation therapy. Moreover, the restenosis rates were reduced, but the restenotic process was not eliminated. Coronary stents eluting the anti-proliferative agent rapamycin have demonstrated for the first time, that restenosis rates of zero percent are achievable after percutaneous revascularization procedures. Thus, it is intriguing to believe that the elimination of restenosis may have become reality. The purpose of this review is to discuss, whether a stent eluting drugs should be considered as the "magic bullet" for prevention of restenosis after PTCA.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Drug Delivery Systems; Equipment Design; Humans; Preventive Medicine; Sirolimus; Stents

Despite dramatic improvements in catheter and stent technology, in-stent restenosis continues to hamper initial procedural success in 10% to 50% of patients undergoing coronary intervention. Recent breakthroughs in polymer science and local drug delivery have shown tremendous promise in the long-sought-after goal of delivering antirestenotic therapy directly from a stent. Clinical trials examining several novel antirestenotic agents, particularly sirolimus and paclitaxel, have shown astonishing reduction in restenosis following stenting. Through examination of the clinical experience to date, we may gain insight into the current and future utility of drug-eluting stents in our clinical practice.

Topics: Angiogenesis Inhibitors; Clinical Trials as Topic; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Polymers; Sirolimus; Stents; Treatment Outcome

Sirolimus (rapamycin), a macrolide antibiotic with known potent immunosuppressive properties, acts in the first phase (G1) of the cell cycle, blocking its further progression to the phase of DNA synthesis (S). In experimental models, rapamycin is effective in inhibiting smooth muscle cell proliferation and migration after vessel wall injury with balloon angioplasty. These results lead to the clinical application of sirolimus-eluting stents in 45 patients in Sao Paulo and Rotterdam (FIM Registry) and 238 patients in a randomized, European multicenter trial (RAVEL). These trials showed, by angiography and intravascular ultrasound, almost complete abolition of in-stent late hyperplasia up to one year after the procedure. In this review, we describe the experimental and clinical results of sirolimus-eluting stents including our experience of 26 stents implanted in 17 patients. In elective de novo lesions has shown remarkably clear lumens at follow-up angiography and intravascular ultrasound within the stented segments were observed with no lesion progression at the stent margins or thrombosis after a 2 month regimen of aspirin, and ticlopodine or clopidogrel. New large-scale ongoing clinical trials will investigate the efficacy of sirolimus-eluting stents in lesions that are traditionally associated with high restenosis rates after stent implantation, such as long lesions, bifurcations and instent restenosis.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Animals; Aspirin; Clopidogrel; Coronary Angiography; Coronary Disease; Coronary Restenosis; Disease Models, Animal; Drug Delivery Systems; Follow-Up Studies; Humans; Immunosuppressive Agents; Injections, Intramuscular; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Rats; Sirolimus; Stents; Swine; Thrombosis; Ticlopidine; Time Factors; Ultrasonography, Interventional

Coronary stent implantation has become a well established therapy in the management of coronary artery disease (CAD). Although the Stent Restenosis Study (STRESS) and Belgium-Netherlands Stent (BENESTENT) trials demonstrated convincingly that stenting is superior to percutaneous transluminal coronary angioplasty with respect to restenosis in de novo lesions, there is, however, still a high incidence (10 to 50%) of restenosis following stent implantation. Improvements in stent design and implantation techniques resulted in an increase in the use of coronary stents and today, in most centers in the US and Europe, stenting has become the predominant form of nonsurgical revascularization accounting for about 80% of all percutaneous coronary intervention procedures. Coronary stents provide luminal scaffolding that virtually eliminates elastic recoil and remodelling. Stents, however, do not decrease neointimal hyperplasia and in fact lead to an increase in the proliferative comportment of restenosis. Agents that inhibit cell-cycle progression indirectly have also been tested as inhibitors of vascular proliferation. When coated onto stents, sirolimus, a macrolide antibiotic with immunosuppressive properties, and paclitaxel and dactinomycin, both chemotherapeutic agents, induced cell-cycle arrest in smooth muscle cells (SMC) and inhibited neointimal formation in animal models. Preliminary clinical studies with drug-eluting stents produced dramatic results eliminating restenosis in large and mid-size arteries. Quantitative coronary angiography and intravascular ultrasound demonstrated virtually complete inhibition of tissue growth at 6 and 12 months after sirolimus-eluting stent implantation. Results are also very encouraging with paclitaxel-coated stents. However, it needs to be proven that current drug-eluting stents will produce similar results in 'real life' interventional practice (long lesions, lesions in small vessels, in vein grafts, chronic total occlusions, and bifurcated and ostial lesions). The ongoing randomized, double-blind sirolimus-coated Bx Velocity trade mark balloon expandable stent in the treatment of patients with de novo coronary artery lesions (SIRIUS) trial may answer some of these concerns. With further improvements, including the expansion of drug-loading capacity, double coatings and coatings with programmable pharmacokinetic capacity using advances in nanotechnology (which may allow for more precise and controlled release of less toxic

Topics: Angioplasty, Balloon, Coronary; Animals; Antineoplastic Agents; Coronary Restenosis; Dactinomycin; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents

Topics: Animals; Anti-Bacterial Agents; Catheter Ablation; Cells, Cultured; Coronary Restenosis; Humans; Muscle, Smooth, Vascular; Sirolimus; Stents

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Division; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Restenosis; Depression, Chemical; Humans; Immunosuppressive Agents; Infusion Pumps, Implantable; Muscle, Smooth, Vascular; Paclitaxel; Sirolimus; Stents

The implantation of radioactive stents was the first procedure of a coronary brachytherapy in Europe examined in multicenter clinical trials.. After more than 400 patients with radioactive stents were analyzed, it became clear that overall restenosis rates were not reduced. A new phenomenon called the "edge effect" or "candy-wrapper" effect was discovered, which later was also described for catheter-based brachytherapy. Currently, the implantation of radioactive stents for the prevention of restenosis cannot be recommended.. Although technical improvements of radioactive stents are theoretically possible, novel drug coated stents may overcome any future research of stent-based radiotherapy. Drug eluting stents induce antiproliferative effects beyond the stent margins. Edge effects were not observed in preliminary trials. However, long-term results need to be awaited.

Topics: Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Brachytherapy; Coronary Angiography; Coronary Restenosis; Humans; Immunosuppressive Agents; Phosphorus Radioisotopes; Pilot Projects; Randomized Controlled Trials as Topic; Sirolimus; Stainless Steel; Stents

Stent implantation has become the new standard angioplasty procedure. In-stent re-stenosis remains the major limitation of coronary stenting. Re-stenosis is related to patient-, lesion- and procedure-specific factors. Patient-specific factors can not be influenced to any extent. Procedure-specific factors are affected by implantation technique and stent characteristics. Design and material influence vascular injury and humoral and cellular response. Radiation has been shown to have inhibitory effects on smooth muscle cell growth and neo-intima formation, but in clinical trials the outcome has been hampered by re-stenosis at the edges of the radioactive stent ('candy wrapper'). New approaches target pharmacological modulation of local vascular biology by local administration of drugs. This allows for drug application at the precise site and time of vessel injury. Systemic release is minimal and this may reduce the risk of toxicity. The drug and the delivery vehicle must fulfil pharmacological, pharmacokinetic and mechanical requirements and the application of eluting degradable matrices seems to be a possible solution. Numerous pharmacological agents with antiproliferative properties are currently under clinical investigation, e.g. actinomycin D, rapamycin or paclitaxel. Another approach is for stents to be made of biodegradable materials as an alternative to metallic stents. Their potential long-term complications, such as in-stent re-stenosis and the inaccessibility of the lesion site for surgical revascularization, needs to be assessed. Current investigational devices and the line of (pre)clinical investigation are discussed in detail. Currently, there is little experimental, and only preliminary clinical, understanding of the acute and long-term effects of drug-eluting or biodegradable stents in coronary arteries. The clinical benefit of these approaches still has to be proven.

Topics: Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Antineoplastic Agents; Biodegradation, Environmental; Coronary Restenosis; Dactinomycin; Drug Delivery Systems; Equipment Design; Humans; Myocardial Ischemia; Paclitaxel; Protein Synthesis Inhibitors; Sirolimus; Stents

Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Biolimus A9™ (BA9), a sirolimus analogue with enhanced lipophilicity, may facilitate enhanced local drug delivery into vascular tissue. A novel DCB coated with Biolimus A9™ represents an alternative to traditional paclitaxel- and sirolimus-coated devices. Hence, we sought to investigate the safety and efficacy of this novel DCB in the treatment of coronary ISR.. REFORM (NCT04079192) is a prospective, multicenter, single blind, randomized controlled trial comparing the BA9-DCB (Biosensors Europe SA, Morges, Switzerland) to the paclitaxel-coated SeQuent® Please DCB (Braun Melsungen AG, Germany) in the treatment of coronary ISR. A total of 201 patients with coronary artery disease and an indication for interventional treatment of ISR in a bare-metal stent (BMS) or drug-eluting stent (DES) have been randomized 2:1 to receive treatment with the BA9- or the paclitaxel-DCB comparator. Patients were enrolled across 24 investigational centers in Europe and Asia. The primary endpoint is percent diameter stenosis (%DS) of the target segment as assessed by quantitative coronary angiography (QCA) at 6 months. Key secondary endpoints are in-stent late lumen loss, binary restenosis, target lesion failure, target vessel failure, myocardial infarction and death at 6 months. Subjects will be followed for 24 months from enrolment.. The REFORM trial will seek to prove that the BA9-DCB is non-inferior to the standard paclitaxel-DCB comparator in the treatment of coronary ISR with respect to %DS at 6 months and has similar safety characteristics.

Topics: Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Pharmaceutical Preparations; Prospective Studies; Single-Blind Method; Sirolimus; Treatment Outcome

Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is a widely adopted strategy for the treatment of de novo coronary artery disease. DES implantation conveys an inherent risk for short- and long-term complications, including in-stent restenosis and stent thrombosis. Drug-coated balloons are emerging as an alternative approach to fulfill the "leaving nothing behind" principle and avoid long-term DES-related complications.. TRANSFORM II is an investigator-initiated, multicenter, noninferiority, randomized clinical trial, testing a sirolimus-coated balloon (SCB) versus the standard of care for native coronary vessels with a 2-3 mm diameter, in terms of 12-month target lesion failure (TLF; primary endpoint) and net adverse cardiovascular events (coprimary endpoint). Patients undergoing PCI will be randomized to be treated with either SCB or new-generation everolimus-eluting stent and will be followed up clinically for up to 60 months. Assuming a TLF rate of 8% at 12 months with DES, a sample size of 1325 patients was chosen to ensure an 80% power to detect a 1.5% lower incidence in the SCB group with a type I error rate of 0.05. The TRANSFORM II trial is registered on clinicaltrials.gov (identification number NCT04893291). Several substudies, including an optical coherence tomography assessment at 9 months (intracoronary imaging substudy), will investigate the study device in different clinical and lesion settings.. The randomized TRANSFORM II trial will determine whether a novel SCB is noninferior to a current everolimus-eluting stent when adopted for the treatment of de novo lesions in coronary vessels with a diameter between 2 and 3 mm.

Topics: Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

Topics: Aged; Aspirin; Biodegradable Plastics; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Humans; Immunosuppressive Agents; Male; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Sirolimus

To evaluate the long-term safety and efficacy of the novel combined sirolimus-eluting endothelial progenitor cell capture Combo stent (OrbusNeich, Fort Lauderdale, FL) at 5 years in the REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coated bio-Engineered stEnt) trial.. Drug-eluting stents have limited restenosis and reintervention but are complicated by late and very late thrombosis and accelerated neoatherosclerosis. Alternative or adjunctive technologies are needed to address these limitations.. A total of 183 patients with de novo lesions in native coronary arteries were randomized 2:1 to Combo (n = 124) or Taxus Liberté (n = 59). Primary endpoint was 9 month angiographic in-stent late lumen loss and the secondary endpoint was the occurrence of major adverse events (MACE) through 5-year follow-up.. Compared with Taxus, after 5 years the Combo stent was associated with similar rates of MACE (18.3% vs. 16.9%, p = .89), cardiac death (0.8% vs. 5.1%, p = .07), myocardial infarction (4.1% vs. 3.4%, p = .81), target lesion (9.4% vs. 10.2%, p = .78), and target vessel revascularization (14.4% vs. 11.9%, p = .73). No cases of definite stent thrombosis were reported in the Combo group. The follow-up rate at 5 years was 97.7%.. At 5-year follow-up, the Combo stent remained clinically safe and effective with an overall low rate of MACE comparable to Taxus.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Endothelial Progenitor Cells; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Drug-coated balloons (DCB) may avoid stent-associated long-term complications. This trial compared the clinical outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) treated with either DCB or stents.. A total of 210 patients with NSTEMI were enrolled in a randomised, controlled, non-inferiority multicentre trial comparing a paclitaxel iopromide-coated DCB with primary stent treatment. The main inclusion criterion was an identifiable culprit lesion without angiographic evidence of large thrombus. The primary endpoint was target lesion failure (TLF; combined clinical endpoint consisting of cardiac or unknown death, reinfarction, and target lesion revascularisation) after nine months. Secondary endpoints included total major adverse cardiovascular events (MACE) and individual clinical endpoints. Mean age was 67±12 years, 67% were male, 62% had multivessel disease, and 31% were diabetics. One hundred and four patients were randomised to DCB, 106 to stent treatment. In the stent group, 56% of patients were treated with BMS, 44% with current-generation DES. In the DCB group, 85% of patients were treated with DCB only whereas 15% underwent additional stent implantation. During a follow-up of 9.2±0.7 months, DCB treatment was non-inferior to stent treatment with a TLF rate of 3.8% versus 6.6% (intention-to-treat, p=0.53). There was no significant difference between BMS and current-generation DES. The total MACE rate was 6.7% for DCB versus 14.2% for stent treatment (p=0.11), and 5.9% versus 14.4% in the per protocol analysis (p=0.056), respectively.. In patients with NSTEMI, treatment of coronary de novo lesions with DCB was non-inferior to stenting with BMS or DES. These data warrant further investigation of DCB in this setting, in larger trials with DES as comparator (ClinicalTrials.gov Identifier: NCT01489449).

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Metals; Middle Aged; Non-ST Elevated Myocardial Infarction; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

Topics: Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Treatment Outcome

The pathomechanisms underlying restenosis of the bioabsorbable sirolimus-eluting metallic scaffold (Magmaris) remain unknown. Using serial optical coherence tomography, we investigated causes of restenosis, including the contribution of late scaffold recoil versus neointimal hyperplasia.. Patients enrolled in BIOSOLVE-II undergoing serial angiography and optical coherence tomography (post-intervention and follow-up: 6 months and/or 1 year) were analyzed. Patients were divided into 2 groups according to angiographic in-scaffold late lumen loss (LLL) <0.5 or ≥0.5 mm. End points were late absolute scaffold recoil and neointimal hyperplasia area as assessed by optical coherence tomography.. In addition to neointimal hyperplasia, late scaffold recoil contributed significantly to LLL of sirolimus-eluting absorbable metal scaffolds. The extent of late scaffold recoil was dependent on the underlying plaque morphology and was the highest among fibrotic lesions. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01960504.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Female; Fibrosis; Humans; Male; Metals; Middle Aged; Myocardial Ischemia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The novel sirolimus-eluting ultra-high molecular weight APTITUDE bioreabsorbable vascular scaffold (BRS) displays higher mechanical strength, expansion capabilities and resistance to fracture compared to other BRS technologies. RENASCENT II is a prospective, multicentre first-in-human clinical study evaluating the clinical performance of the APTITUDE BRS in the treatment of single de novo coronary lesions among patients undergoing percutaneous coronary intervention.. The APTITUDE BRS was tested in a prospective study in two countries (Italy and Colombia). Study objectives were angiographic in-scaffold late lumen loss (IS-LLL) measured by quantitative coronary angiography (QCA) and target vessel failure (TVF) defined as the composite rate of cardiac death, target vessel myocardial infarction (TV-MI) or ischaemia-driven target lesion revascularisation (TLR) at 9 and 24 months. A total of 60 patients were enrolled. All patients underwent lesion predilatation and 46 patients (76.7%) underwent post-dilatation. Clinical device and procedural success were 98.3% (59/60 patients) and 100%, respectively. Angiographic late lumen loss was 0.19±0.26 mm at 9 months and 0.3±0.41 mm at 24 months. At 9 months, TVF occurred in 2/59 patients (3.4%) due to TV-MI but there was no TLR. No further cases of TVF, MACE or stent thrombosis were reported up to 24-month follow-up.. In this multicentre prospective study, the APTITUDE BRS was shown to be safe and effective in the treatment of single coronary lesions at 24-month clinical follow-up.

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Treatment of bifurcation lesions is technically challenging and has been associated with an increased risk of adverse events. We sought to evaluate the clinical and angiographic outcomes of patients who underwent bifurcation lesion provisional treatment in the BioNIR Ridaforolimus Eluting Coronary Stent System in Coronary Stenosis trial. A prospective, multicenter, 1:1 randomized trial was conducted to evaluate the safety and efficacy of ridaforolimus-eluting stents (RES) versus zotarolimus-eluting stents (ZES). Enrollment of bifurcation lesions treated with a provisional 1-stent technique was allowed. Bifurcation lesions were analyzed by an angiographic core laboratory. Outcomes were analyzed according to the presence of a bifurcation lesion treatment. Study population included 686 (35.8%) patients with and 1,228 (64.2%) patients without bifurcation lesion treatment. Procedural success was high and similar between groups. In 2 years, there was no difference in the rate of target lesion failure between the bifurcation and nonbifurcation groups (7.6% vs 7.3%, respectively, p = 0.81) regardless of the presence of side branch stenosis ≥50%. In 159 patients with angiographic follow-up, there was no difference in the rate of binary restenosis between groups (9.0% vs 9.2%, p = 0.96). Rates of target lesion failure at 1-year were similar with ZES and RES, and consistent in patients with and without bifurcation lesions (p

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus

This investigator-driven, multicenter, randomized, single-blind, controlled trial randomized ST-segment-elevation myocardial infarction patients 1:1 to SES or MgBRS at 11 academic centers. The primary end point was the rate of increase (≥3%) after nitroglycerin in mean lumen diameter of the in-stent/scaffold segment at 12 months with superiority of MgBRS over SES in the as-treated population. The main secondary end points included angiographic parameters of restenosis, device-oriented composite end point, their individual components, and device thrombosis rate. Besides, endothelial-dependent vasomotor response to acetylcholine (ie, endothelial function) was also assessed in a subgroup of patients (n=69).. When compared to SES, MgBRS demonstrated a higher capacity of vasomotor response to pharmacological agents (either endothelium-independent or endothelium-dependent) at 1 year. However, MgBRS was associated with a lower angiographic efficacy, a higher rate of target lesion revascularization, without thrombotic safety concerns.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT03234348.

Topics: Absorbable Implants; Acetylcholine; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Incidence; Magnesium; Male; Middle Aged; Nitroglycerin; Polyesters; Risk Factors; Sample Size; Sirolimus; ST Elevation Myocardial Infarction; Thrombectomy; Tissue Scaffolds; Vasodilation; Vasodilator Agents; Vasomotor System

The long-term outcomes of biolimus-eluting stents (BESs) with biodegradable polymer as compared with bare-metal stent (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain unknown.. We performed a 5-year clinical follow-up of 1157 patients (BES: N = 575 and BMS: N = 582) included in the randomized COMFORTABLE AMI trial. Serial intracoronary imaging of stented segments using both intravascular ultrasound (IVUS) and optical coherence tomography performed at baseline and 13 months follow-up were analysed in 103 patients. At 5 years, BES reduced the risk of major adverse cardiac events [MACE; hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.39-0.79, P = 0.001], driven by lower risks for target vessel-related reinfarction (HR 0.44, 95% CI: 0.22-0.87, P = 0.02) and ischaemia-driven target lesion revascularization (HR 0.41, 95% CI: 0.25-0.66, P < 0.001). Definite stent thrombosis (ST) was recorded in 2.2% and 3.9% (HR 0.57, 95% CI: 0.28-1.16, P = 0.12) with no differences in rates of very late definite ST (1.3% vs. 1.6%, P = 0.77). Optical coherence tomography showed no difference in the frequency of malapposed stent struts at follow-up (BES 0.08% vs. BMS 0.02%, P = 0.10). Uncovered stent struts were rarely observed but more frequent in BES (2.1% vs. 0.15%, P < 0.001). In the IVUS analysis, there was no positive remodelling in either group (external elastic membrane area change BES: -0.63 mm2, 95% CI: -1.44 to 0.39 vs. BMS -1.11 mm2, 95% CI: -2.27 to 0.04, P = 0.07).. Compared with BMS, the implantation of biodegradable polymer-coated BES resulted in a lower 5-year rate of MACE in patients with STEMI undergoing primary percutaneous coronary intervention. At 13 months, vascular healing in treated culprit lesions was almost complete irrespective of stent type.. http://www.clinicaltrials.gov. Unique identifier: NCT00962416.

Topics: Absorbable Implants; Acute Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Metals; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Sirolimus; ST Elevation Myocardial Infarction; Stents; Thrombosis; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Stenting small-vessel lesions has an increased adverse cardiovascular event risk. Very thin-strut or ultrathin-strut drug-eluting stents might reduce this risk, but data are scarce.. To assess the outcome of all-comer patients with small coronary vessel lesions treated with 3 dissimilar types of drug-eluting stents.. This is a prespecified substudy of the Comparison of Biodegradable Polymer and Durable Polymer Drug-eluting Stents in an All Comers Population (BIO-RESORT) trial, an investigator-initiated, randomized, patient-blinded comparative clinical drug-eluting stent trial. Patients treated with ultrathin-strut sirolimus-eluting stents, very thin-strut everolimus-eluting stents, or previous-generation thin-strut zotarolimus-eluting stents were enrolled from December 2012 to August 2015. This multicenter trial was conducted in 4 Dutch centers for cardiac intervention. Of all 3514 all-comer BIO-RESORT participants, 1506 patients with treatment in at least 1 small-vessel lesion (reference vessel <2.5 mm) were included. Data were analyzed between September 2018 and February 2019.. Target lesion failure at 3-year follow-up, a composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization, analyzed by Kaplan-Meier methods.. In 1452 of 1506 participants (96.4%) (1057 men [70.2%]; 449 women [29.8%]; mean [SD] age, 64.3 [10.4] years), follow-up was available. Target lesion failure occurred in 36 of 525 patients (7.0%) treated with sirolimus-eluting stents, 46 of 496 (9.5%) with everolimus-eluting stents, and 48 of 485 (10.0%) with zotarolimus-eluting stents (sirolimus-eluting vs zotarolimus-eluting hazard ratio [HR], 0.68; 95% CI, 0.44-1.05; P = .08; everolimus-eluting vs zotarolimus-eluting HR, 0.93; 95% CI, 0.62-1.39; P = .72). There was a difference in target lesion revascularizations between sirolimus-eluting and zotarolimus-eluting stents (2.1% vs 5.3%; HR, 0.40; 95% CI, 0.20-0.81; P = .009) that emerged after the first year of follow-up (1.0% vs 3.7%; P = .006); multivariate analysis showed that sirolimus-eluting stent implantation was independently associated with a lower target lesion revascularization rate at 3-year follow-up (adjusted HR, 0.42; 95% CI, 0.20-0.85; P = .02). In the everolimus-eluting stents, the revascularization rate was 4.0% (vs zotarolimus-eluting, HR, 0.74; 95% CI, 0.41-1.34; P = .31). There was no significant between-stent difference in cardiac death, target vessel myocardial infarction, or stent thrombosis.. Patients stented in small coronary vessels experienced fewer repeated revascularizations if treated with ultrathin-strut sirolimus-eluting stents vs previous generation thin strut zotarolimus-eluting stents. Further research is required to evaluate the potential effect of particularly thin stent struts.. ClinicalTrials.gov identifier: NCT01674803.

Topics: Absorbable Implants; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Sirolimus; Treatment Outcome

A second iteration of a sirolimus-eluting stent (SES) that has a biodegradable PLGA polymer coating with an electrografting base layer on a thin-strut (80 µm) cobalt-chromium platform (BuMA Supreme; SINOMED, Tianjin, China) has been developed. This first-in-man trial aimed to assess the efficacy and safety of the novel device.. This randomised, multicentre, single-blinded, non-inferiority trial compared the BuMA Supreme SES versus a contemporary durable polymer zotarolimus-eluting stent (ZES) in terms of angiographic in-stent late lumen loss (LLL) at nine-month follow-up as the primary endpoint. A total of 170 patients were randomly allocated to treatment with either SES (n=83) or ZES (n=87). At nine-month angiographic follow-up, in-stent LLL was 0.29±0.33 mm in the SES group and 0.14±0.37 mm in the ZES group (pnon-inferiority=0.45). The in-stent percent diameter stenosis and the binary restenosis rate of the two treatment arms were similar (19.2±12.0% vs. 16.1±12.6%, p=0.09, and 3.3% vs. 4.4%, p=1.00, respectively). At 12-month clinical follow-up, there was no difference between treatment arms with regard to the device-oriented composite clinical endpoint (4.9% vs. 5.7%; p=0.72).. The PIONEER trial did not meet its primary endpoint in terms of in-stent LLL at nine-month follow-up. However, this result did not translate into any increase in restenosis rate or impairment in 12-month clinical outcomes.

Topics: Absorbable Implants; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus

To assess the safety and efficacy of the novel Resolute (R-) Onyx drug-eluting stent (DES).. The R-Onyx DES consists of a composite wire with an outer shell of cobalt chromium alloy and a platinum-iridium inner core to enhance radiopacity, with thinner, swaged struts and modified stent geometry compared with the predicate Resolute DES, resulting in a slightly lower total drug load in most sizes.. This was a prospective, single-arm non-inferiority trial compared with a historical control. Patients with stable angina/ischemia and up to 2 de novo target lesions ≤35 mm long with reference vessel diameter (RVD) of 2.25-4.2 mm were enrolled. The primary endpoint was late lumen loss at 8-month follow-up. Propensity-score adjusted outcomes from the single-arm RESOLUTE-US trial served as the control.. Seventy-five patients (85 lesions) were enrolled. Mean patient age was 66 ± 9 years, 73% were male, and 32% had diabetes. Mean lesion length was 14.28 ± 6.68 mm, mean RVD was 2.57 ± 0.48 mm, and 86% of lesions were class B2/C. In-stent late lumen loss at 8 months was 0.24 ± 0.39 mm with R-Onyx DES compared with 0.36 ± 0.52 mm with Resolute DES (P < 0.001 for noninferiority, P = 0.029 for superiority). At 8 months, clinically driven target lesion revascularization occurred in 3 patients (4.0%) and target lesion failure occurred in 5 patients (6.7%).. In-stent late lumen loss is non-inferior, and appears to be superior, with the thin-strut novel composite wire R-Onyx DES compared with Resolute DES. Continued evolution of stent design can improve angiographic outcomes in complex lesions, even in the current era of next-generation DES.

Topics: Aged; Angina, Stable; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Iridium; Male; Middle Aged; Percutaneous Coronary Intervention; Platinum; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; United States

Quantitative flow ratio (QFR) based on three-dimensional quantitative coronary angiography (3D-QCA) is a novel method to assess physiological functionality after treatment with stents. The current study aimed to evaluate the difference in physiological functionality nine months after implantation of a bioresorbable polymer-based sirolimus-eluting stent with an electrografting base layer (BuMA Supreme: B-SES) versus a durable polymer-based zotarolimus-eluting stent (Resolute: R-ZES).. The current post hoc analysis was performed in the PIONEER randomised trial (1:1 randomisation to B-SES [83 patients/95 lesions] and R-ZES [87 patients/101 lesions]). QFR was measured in stented vessels in both arms at preprocedural, post-procedural and nine-month angiography without pharmacologically induced hyperaemia (contrast QFR). At nine months, both the values of QFR distal to the stent (B-SES: 0.89±0.10 vs. R-ZES: 0.89±0.11, p=0.97) and the number of vessels with QFR ≤0.8 were not significantly different between the two groups (11.0% vs. 12.8%, p=0.72), while the in-stent binary restenosis rate was also comparable (3.7% vs. 3.5%, p=1.00). QFR gradient across the device (∆QFR) at nine months was also similar between the groups (B-SES: 0.03±0.04 vs. R-ZES: 0.03±0.07, p=0.95).. Quantitative flow assessment nine months after stenting did not differ between B-SES and R-ZES, despite a significant difference in in-stent late lumen loss.

Topics: Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

We aimed to compare the long-term outcomes of the novel biodegradable polymer cobalt-chromium sirolimus-eluting stent (BP-SES) versus the durable polymer sirolimus-eluting stent (DP-SES) in the I-LOVE-IT2 trial.. Comparisons of the long-term safety and efficiency of the BP-DES versus the DP-DES are limited.. A total of 2,737 patients eligible for coronary stenting were randomized to the BP-SES or DP-SES group at a 2:1 ratio. The primary endpoint of target lesion failure (TLF) was defined as a composite of cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularization.. A three-year clinical follow-up period was available for 2,663 (97.3%) patients. There were no significant differences in TLF (8.9% vs. 8.6%, P = 0.81), patient-oriented composite endpoint (PoCE) (15.2% vs.14.5%, P = 0.63), or individual components between the BP-SES and DP-SES. Definite/probable stent thrombosis (ST) was low and similar at 3 years (0.8% vs. 1.0%, P = 0.64). Landmark analysis of 1-3 years showed that the TLF (2.7% vs. 2.6%, P = 0.81), PoCE (6.2% vs. 5.1%, P = 0.28), and definite/probable ST (0.4% vs. 0.4%, P = 1.00) were comparable between the 2 arms.. In this prospective randomized trial, the BP-SES showed similar clinical results versus the DP-SES in terms of safety and efficacy outcomes over a 3-year follow-up period.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Agents; China; Chromium Alloys; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Recurrence; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The authors sought to evaluate the safety and effectiveness of the NeoVas bioresorbable scaffold (BRS) compared with metallic drug-eluting stents.. BRS have the potential to improve very late outcomes compared with metallic drug-eluting stents, but some BRS have been associated with increased rates of device thrombosis before complete bioresorption. NeoVas is a new poly-l-lactic acid BRS that elutes sirolimus from a poly-D, l-lactide coating.. Eligible patients with a single de novo native coronary artery lesion with a reference vessel diameter 2.5 to 3.75 mm and a lesion length ≤20 mm were randomized 1:1 to NeoVas BRS versus cobalt-chromium everolimus-eluting stents (CoCr-EES). Angiographic follow-up was performed in all patients at 1 year. The primary endpoint was angiographic in-segment late loss (LL), and the major secondary endpoint was the rate of angina. Baseline and follow-up optical coherence tomography and fractional flow reserve were performed in a pre-specified subgroup of patients.. The authors randomized 560 patients at 32 centers to treatment with NeoVas (n = 278) versus CoCr-EES (n = 282). One-year in-segment LL with NeoVas and CoCr-EES were 0.14 ± 0.36 mm versus 0.11 ± 0.34 mm (difference 0.03 mm; upper 1-sided 97.5% confidence interval 0.09 mm; p. The NeoVas BRS was noninferior to CoCr-EES for the primary endpoint of 1-year angiographic in-segment LL, and resulted in comparable 1-year clinical outcomes, including recurrent angina. (NeoVas Bioresorbable Coronary Scaffold Randomized Controlled Trial; NCT02305485).

Topics: Absorbable Implants; Aged; Cardiac Catheterization; Cardiovascular Agents; China; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Fractional Flow Reserve, Myocardial; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Polyesters; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents (ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts).. The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices.. In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated.. Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; p. At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Netherlands; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

The aim of this study was to evaluate the efficacy and safety of the BioNIR stent compared with the Resolute Integrity stent for the treatment of coronary artery disease.. This first-in-human, multicentre, single-blind randomised non-inferiority trial was performed in Europe and Israel. Patients with stable coronary artery disease or acute coronary syndromes were randomly assigned to treatment with BioNIR or Resolute Integrity stents in a 2:1 fashion. The primary endpoint was angiographic in-stent late lumen loss (LLL) at six months. Three hundred and two patients were randomised, of whom 261 (86.0%) underwent six-month angiographic follow-up. The BioNIR stent was non-inferior to the Resolute Integrity stent for the primary endpoint of in-stent LLL at six months (0.04±0.30 mm vs. 0.03±0.31 mm, respectively, pnoninferiority<0.0001). At 12-month follow-up, target lesion failure occurred in 3.4% in the BioNIR group and 5.9% in the Resolute Integrity group (p=0.22). Rates of MACE were similar between the BioNIR and Resolute Integrity groups (4.3% vs. 5.9%, respectively, p=0.45).. The BioNIR stent was non-inferior to the Resolute Integrity stent for the primary endpoint of angiographic in-stent LLL at six months. Clinical outcomes at one year were comparable between the two groups.

Topics: Adult; Aged; Aged, 80 and over; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Treatment Outcome

Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer.. Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9-eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent at 2 to 6 months (. Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small sample size.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01742507.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Hong Kong; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The PRISON-IV trial showed inferior outcome in patients with chronic total occlusions (CTOs) treated with the ultrathin-struts (60 μm for stent diameter ≤3 mm, 81μm >3 mm) hybrid-sirolimus eluting stents (SES) compared with everolimus eluting stents (EES, 81 μm). The aim of this study is to investigate if the use of smaller stents (≤3 mm) was responsible for the inferior outcome reported in the trial.. In the PRISON-IV trial 330 patients with CTO lesion were randomized 1:1 to receive either hybrid-SES or EES. The hybrid-SES failed to reach the non-inferiority primary endpoint of in-segment late lumen loss (LLL) at 9-month angiographic follow-up. In this sub-analysis, we divided the population according to the different size of stents implanted in those receiving only stents with diameter ≤3 mm (Group-A, 178 patients), only stents >3 mm (Group-B, 59 patients), and those receiving stents of both sizes (Group-C, 93 patients).. The present analysis suggests that the inferior performance of the ultra-thin hybrid-SES in CTO-PCI is particularly pronounced when smaller stent (≤3 mm diameter) are adopted, if compared with EES.

Topics: Aged; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome; Vascular Diseases

The aim of this study was to provide contemporary outcome data for patients with de novo coronary disease and Medina 1,1,1 lesions who were treated with a culotte two-stent technique, and to compare the performance of two modern-generation drug-eluting stent (DES) platforms, the 3-connector XIENCE and the 2-connector SYNERGY.. Patients with Medina 1,1,1 bifurcation lesions who had disease that was amenable to culotte stenting were randomised 1:1 to treatment with XIENCE or SYNERGY DES. A total of 170 patients were included. Technical success and final kissing balloon inflation occurred in >96% of cases. Major adverse cardiovascular or cerebrovascular events (MACCE: a composite of death, myocardial infarction [MI], cerebrovascular accident [CVA] and target vessel revascularisation [TVR]) occurred in 5.9% of patients by nine months. The primary endpoint was a composite of death, MI, CVA, target vessel failure (TVF), stent thrombosis and binary angiographic restenosis. At nine months, the primary endpoint occurred in 19% of XIENCE patients and 16% of SYNERGY patients (p=0.003 for non-inferiority for platform performance).. MACCE rates for culotte stenting using contemporary everolimus-eluting DES are low at nine months. The XIENCE and SYNERGY stents demonstrated comparable performance for the primary endpoint.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Sirolimus; Treatment Outcome

Although several studies have shown positive outcomes after the use of drug-coated balloons (DCB) for in-stent restenosis (ISR), data on randomised controlled trials versus latest-generation drug-eluting stents (DES) are limited. Therefore, in this randomised trial, we sought to evaluate whether a butyryl-tri-hexyl citrate (BTHC)-based paclitaxel DCB is non-inferior to a biodegradable polymer sirolimus-eluting stent (BP-SES) therapy in patients with ISR in either a bare metal stent (BMS) or DES.. A total of 229 patients with ISR in BMS or DES from 13 German centres and one Latvian centre were 2:1 randomly allocated to DCB (n=157) or DES (n=72). The primary efficacy endpoint was defined as in-stent late lumen loss (LLL) at six months, and the primary safety endpoint was target lesion failure (TLF) at 12 months. LLL in the DCB arm was 0.03±0.40 mm compared to 0.20±0.70 mm in the DES arm (p=0.40). DCB proved to be non-inferior to DES (Δ = -0.17±0.52 mm, 97.5% CI -∞; -0.01]; p<0.0001). At 12 months, Kaplan-Meier TLF estimates were 16.7% in the DCB arm and 14.2% in the DES arm (p=0.65) and remained similar at 18 months (DCB versus DES: 17.4% versus 19.5%, p=0.88).. In patients with DES or BMS ISR, treatment with a paclitaxel DCB showed similar LLL at six months and TLF rates up to 18 months compared to a second-generation sirolimus DES.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

This study aimed to establish the early healing and neointimal transformation profile of the new polymer-free BioFreedom stent through sequential optical coherence tomography (OCT) within the first nine months following stent implantation.. We randomly assigned 104 BFS recipients to one of five groups with angiography and OCT follow-up at 1, 2, 3, 4, or 5 months, together with another follow-up for all at nine months. The primary endpoint was the degree of OCT-detected strut coverage at nine months. From 1, 2, 3, 4, and 5 months, median neointimal strut coverage increased from 85.8, 87.0, 88.6, 96.8 to 97.1%, respectively, to 99.6% (IQR 98.2-99.9) at nine months. At nine months, median percent neointimal volume was 13.0% and angiographic late lumen loss was 0.21±0.30 mm. Major adverse cardiac events (MACE) were limited to one non-cardiac death, one non-ST-elevation myocardial infarction not related to BFS, and two target lesion revascularisations without stent thrombosis (MACE rate 4.0%).. Neointimal strut coverage of the BFS was rapid and the BFS was shown to be clinically safe and effective.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Balloon dilatation or debulking seems to be essential to allow successful stent implantation in calcified coronary lesions. Compared with standard balloon predilatation, debulking using high-speed rotational atherectomy (RA) is associated with higher initial procedural success albeit with higher in-stent late lumen loss at intermediate-term follow-up. Whether modified (scoring or cutting) balloons (MB) could achieve similar procedural success compared with RA is not known. In addition, whether new-generation drug-eluting stents could counterbalance the excessive neointimal proliferation triggered by RA remains to be determined.. We randomly assigned patients with documented myocardial ischemia and severely calcified native coronary lesions undergoing percutaneous coronary intervention to a strategy of lesion preparation using MB or RA followed by drug-eluting stent implantation. Stenting was performed using a third-generation sirolimus-eluting stent with a bioabsorbable polymer. The trial had 2 primary end points: strategy success (defined as successful stent delivery and expansion with attainment of <20% in-stent residual stenosis in the presence of TIMI [Thrombolysis in Myocardial Infarction] 3 flow without crossover or stent failure; powered for superiority) and in-stent late lumen loss at 9 months (powered for noninferiority). Two hundred patients were enrolled at 2 centers in Germany (n=100 in each treatment group). The mean age of the study population was 74.9±7.0 years; 76% were men, and 33.5% had diabetes mellitus. Strategy success was significantly more common in the RA group (81% versus 98%; relative risk of failure with an MB- versus RA-based strategy, 9.5; 95% CI, 2.3-39.7; P=0.0001), but mean fluoroscopy time was longer (19.6±13.4 versus 23.9±12.2 minutes; P=0.03). At 9 months, mean in-stent late lumen loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group ( P=0.21, P=0.02 for noninferiority). Target lesion revascularization (7% versus 2%; P=0.17), definite or probable stent thrombosis (0% versus 0%; P=1.00), and target vessel failure (8% versus 6%; P=0.78) were low and not significantly different between the MB and RA groups.. Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in nearly all patients with severely calcified coronary lesions, is more commonly successful as a primary strategy compared with MB, and is not associated with excessive late lumen loss. A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters and less irradiation. Both strategies are associated with excellent clinical outcome at 9 months.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02502851.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Germany; Humans; Male; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Vascular Calcification

The aim of this study was to evaluate the angiographic efficacy and clinical outcomes of the Restore paclitaxel-coated balloon in a randomized trial designed to enable its approval with an indication for small-vessel disease (SVD).. Higher rates of restenosis and stent thrombosis limit the effectiveness of drug-eluting stent (DES) treatment of SVD. Whether a drug-coated balloon (DCB)-only strategy is effective in de novo SVD is not yet established.. In the noninferiority RESTORE SVD China trial, eligible patients with reference vessel diameter ≥2.25 and ≤2.75 mm were randomized to the Restore DCB or the RESOLUTE Integrity DES in a 1:1 ratio stratified by diabetes and number of lesions treated. Patients with RVD ≥2.00 and <2.25 mm were enrolled in a nested very small vessel registry. Angiographic and clinical follow-up were planned at 9 months and 1 year, respectively, in all patients. The study was powered for the primary endpoint of 9-month in-segment percentage diameter stenosis.. Between August 2016 and June 2017, a total of 230 subjects at 12 sites were randomized to the DCB group (n = 116) or DES group (n = 114); 32 patients were treated with the DCB in the very small vessel cohort. Nine-month in-segment percentage diameter stenosis was 29.6 ± 2.0% with the DCB versus 24.1 ± 2.0% with the DES; the 1-sided 97.5% upper confidence limit of the difference was 10.9%, achieving noninferiority of the DCB compared with the DES (p for noninferiority < 0.001). The DCB and DES had comparable 1-year rates of target lesion failure (4.4% vs. 2.6%, p = 0.72).. In this multicenter randomized trial, the Restore DCB was noninferior to the RESOLUTE DES for 9-month in-segment percentage diameter stenosis. (Assess the Efficacy and Safety of RESTORE Paclitaxel Eluting Balloon Versus RESOLUTE Zotarolimus Eluting Stent for the Treatment of Small Coronary Vessel Disease; NCT02946307).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; China; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Prosthesis Design; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The authors sought to investigate the impact of diabetes mellitus (DM) on outcomes following contemporary drug-eluting stent (DES) implantation in the BIONICS (BioNIR Ridaforolimus Eluting Coronary Stent System in Coronary Stenosis) trial.. Patients with DM are at increased risk for adverse events following percutaneous coronary intervention (PCI).. A prospective, multicenter, 1:1 randomized trial was conducted to evaluate in a noninferiority design the safety and efficacy of ridaforolimus-eluting stents versus zotarolimus-eluting stents among 1,919 patients undergoing PCI. Randomization was stratified to the presence of medically treated DM, and a pre-specified analysis compared outcomes according to the presence or absence of DM up to 2 years.. The overall prevalence of DM was 29.1% (559 of 1,919). DM patients had higher body mass index, greater prevalence of hyperlipidemia and hypertension, and smaller reference vessel diameter. One-year target lesion failure (cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization) was significantly higher among diabetic patients (7.8% vs. 4.2%; p = 0.002), mainly due to higher target lesion revascularization (4.5% vs. 2.0%; p = 0.002). Rates of cardiac death, myocardial infarction, and stent thrombosis did not statistically vary. Among 158 patients undergoing 13-month angiographic follow-up, restenosis rates were 3 times higher in diabetic patients compared with nondiabetic patients (15.2% vs. 4.7%; p = 0.01). Clinical and angiographic outcomes were similar between ridaforolimus-eluting stent- and zotarolimus-eluting stent-treated patients.. Despite advances in interventional therapies, and the implementation of new-generation DES, diabetic patients still have worse angiographic and clinical outcomes compared with nondiabetic patients undergoing PCI.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prevalence; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

The primary objective of this study was to evaluate the safety and effectiveness of the Mirage (Manli Cardiology, Singapore) bioresorbable microfiber sirolimus-eluting scaffold compared with the Absorb (Abbott Vascular, Santa Clara, California) bioresorbable vascular scaffold in the treatment of stenotic target lesions located in native coronary arteries, ranging from ≥2.25 to ≤4.0 mm in diameter. Secondary objectives were to establish the medium-term safety, effectiveness, and performance of the Mirage device.. The current generation of bioresorbable scaffolds has several limitations, such as thick square struts with large footprints that preclude their deep embedment into the vessel wall, resulting in protrusion into the lumen with microdisturbance of flow. The Mirage sirolimus-eluting bioresorbable microfiber scaffold is designed to address these concerns.. In this prospective, single-blind trial, 60 patients were randomly allocated in a 1:1 ratio to treatment with a Mirage sirolimus-eluting bioresorbable microfiber scaffold or an Absorb bioresorbable vascular scaffold. The clinical endpoints were assessed at 30 days and at 6 and 12 months. In-device angiographic late loss at 12 months was quantified. Secondary optical coherence tomographic endpoints were assessed post-scaffold implantation at 6 and 12 months.. Median angiographic post-procedural in-scaffold minimal luminal diameters of the Mirage and Absorb devices were 2.38 mm (interquartile range [IQR]: 2.06 to 2.62 mm) and 2.55 mm (IQR: 2.26 to 2.71 mm), respectively; the effect size (d) was -0.29. At 12 months, median angiographic in-scaffold minimal luminal diameters of the Mirage and Absorb devices were not statistically different (1.90 mm [IQR: 1.57 to 2.31 mm] vs. 2.29 mm [IQR: 1.74 to 2.51 mm], d = -0.36). At 12-month follow-up, median in-scaffold late luminal loss with the Mirage and Absorb devices was 0.37 mm (IQR: 0.08 to 0.72 mm) and 0.23 mm (IQR: 0.15 to 0.37 mm), respectively (d = 0.20). On optical coherence tomography, post-procedural diameter stenosis with the Mirage was 11.2 ± 7.1%, which increased to 27.4 ± 12.4% at 6 months and remained stable (31.8 ± 12.9%) at 1 year, whereas the post-procedural optical coherence tomographic diameter stenosis with the Absorb was 8.4 ± 6.6%, which increased to 16.6 ± 8.9% and remained stable (21.2 ± 9.9%) at 1-year follow-up (Mirage vs. Absorb: d. At 12 months, angiographic in-scaffold late loss was not statistically different between the Mirage and Absorb devices, although diameter stenosis on angiography and on optical coherence tomography was significantly higher with the Mirage than with the Absorb. The technique of implantation was suboptimal for both devices, and future trials should incorporate optical coherence tomographic guidance to allow optimal implantation and appropriate assessment of the new technology, considering the novel mechanical properties of the Mirage.

Topics: Absorbable Implants; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Female; Humans; Indonesia; Malaysia; Male; Middle Aged; Multimodal Imaging; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Data from randomized controlled trials have shown that the ABSORB BVS is non-inferior to Cobalt Chromium everolimus-eluting stents at 2years.. The EVERBIO II trial (Comparison of Everolimus- and Biolimus-Eluting Coronary Stents with Everolimus-Eluting Bioresorbable Vascular Scaffold) is a single-center, assessor-blind, randomized controlled trial enrolling 240 patients with an allocation ration of 1:1:1 conducted at University and Hospital Fribourg, Switzerland. The studied devices were an everolimus-eluting persistent polymer stent (EES), a biolimus-eluting stent with bioabsorbable polymer (BES) and a fully bioresorbable vascular scaffold (BVS). Clinical end points collected at 9months, 12months, and 2years, were academic research consortium defined composites, device thrombosis and target-vessel revascularization. Clinical follow-up at 2years was available in 96% (N=77) of patients in the EES group, in 100% (N=80) in the BES and 99% (N=77) in the BVS group. The device-oriented composite end point of cardiac death, target-vessel myocardial infarction and target-lesion revascularization occurred in 13 (16%) patients treated with EES, in 7 (9%) patients treated with BES and in 16 (21%) patients treated with BVS. There was no significant difference when the metallic stents were compared to the BVS (p=0.12). There was one late scaffold thrombosis throughout the trial in the BVS group, and no definite stent thrombosis in either EES or BES treated patients.. The current analysis shows no significant differences with regard to clinical outcomes at 2years between BVS and the best-in-class metallic DES. Event rates were numerically higher in BVS-treated patients. However, when BVS were compared to BES alone, the occurrence of device related adverse events was significantly increased.

Topics: Absorbable Implants; Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Single-Blind Method; Sirolimus; Time Factors; Tissue Scaffolds; Treatment Outcome

The aim of this study was to explore the safety and efficacy of a dedicated drug-eluting stent for the treatment of coronary lesions with very small reference vessel diameter (RVD).. Smaller RVD is associated with increased risk for restenosis and target lesion failure (TLF) after stent implantation.. This was a prospective, single-arm, multicenter trial of the Resolute Onyx 2.0-mm zotarolimus-eluting stent. The primary endpoint was 12-month TLF, which was compared with a pre-specified performance goal. Subjects with stable or unstable angina or ischemia, target lesions ≤27 mm in length, and RVD ≥2.0 and <2.25 mm were eligible for enrollment. A subset of subjects underwent follow-up angiography at 13 months post-procedure.. A total of 101 subjects with 104 lesions were enrolled. The mean age was 67.3 ± 9.6 years, 47% of subjects had diabetes, the mean lesion length was 12.6 ± 6.3 mm, and the mean RVD was 1.91 ± 0.26 mm. The rate of TLF at 12 months was 5.0%, fulfilling the pre-specified performance goal of 19% (p < 0.001). The rates of target lesion revascularization and target vessel myocardial infarction were 2.0% and 3.0%, respectively. There were no episodes of stent thrombosis. In-stent late lumen loss was 0.26 ± 0.48 mm, and the rate of binary restenosis was 12.0%.. In this first report of a drug-eluting stent with a dedicated size to treat lesions with RVD <2.25 mm, the Resolute Onyx 2.0-mm zotarolimus-eluting stent was associated with a low rate of TLF and late lumen loss, without a signal for stent thrombosis. This novel-sized drug-eluting stent appears to be a feasible option for the treatment of coronary lesions in extremely small vessels. (Medtronic Resolute Onyx 2.0 mm Clinical Study; NCT02412501).

Topics: Aged; Angina, Stable; Angina, Unstable; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; United States

Our aim was to report the long-term safety and efficacy of the biodegradable polymer-coated biolimus- eluting Nobori stent compared to the durable polymer-coated sirolimus-eluting CYPHER stent.. SORT OUT V randomised 2,468 patients 1:1 to the Nobori (n=1,229) versus the CYPHER stent (n=1,239). Clinically driven event detection based on Danish registries was used. The primary endpoint was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularisation). Individual components of the primary endpoint comprise the secondary endpoints. At five-year follow-up, the composite endpoint rate was found to be similar in patients treated with the two study stents (Nobori 182/1,229 [14.8%] vs. CYPHER 197/1,239 [15.8%]; odds ratio [OR] 0.93, 95% CI: 0.75-1.16; p=0.53). The rates of definite stent thrombosis were also found to be similar in patients treated with the two study stents (Nobori 23/1,229 [1.9%] vs. CYPHER 18/1,239 [1.5%]; OR 1.31, 95% CI: 0.70-2.47; p=0.40), as were the other secondary endpoints.. At five-year follow-up, the Nobori stent with a biodegradable polymer coating provided a similar safety and efficacy profile when compared to the durable polymer first-generation CYPHER stent.

Topics: Absorbable Implants; Acute Coronary Syndrome; Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Incidence; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Recurrence; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The aim of this first-in-human study was to assess the safety and effectiveness of the Virtue sirolimus-eluting balloon in a cohort of patients with in-stent restenosis (ISR).. Angioplasty balloons coated with the cytotoxic drug paclitaxel have been widely used for ISR treatment. The Virtue angioplasty balloon (Caliber Therapeutics, New Hope, Pennsylvania) delivers sirolimus in a nanoencapsulated liquid formulation. This clinical trial is the first to examine a sirolimus-eluting balloon for ISR.. In this prospective, single-arm feasibility study at 9 European centers, 50 ISR patients were treated with the Virtue balloon. Angiographic measurements at 6 months are reported, along with 12-month clinical follow-up.. Procedural success in the intention-to-treat population was 100%. The primary safety endpoint was target lesion failure (TLF) (cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization) assessed at 30 days (0%, n = 50). The primary performance endpoint was in-segment late lumen loss (LLL) at 6 months (0.31 ± 0.52 mm; n = 47). Secondary 6-month endpoints include binary restenosis (19.1%), diameter stenosis (30.3 ± 19.9%), and major adverse cardiac events (MACE) (10.2%, n = 49). In the 36-patient per-protocol population (excluding major protocol violations and previously stented ISR), LLL was 0.12 ± 0.33 mm at 6 months. Clinical outcomes at 1 year for the intention-to-treat group were 12.2% TLF and 14.3% MACE and for the per-protocol population were 2.8% TLF and 2.8% MACE.. This first-in-human study showed excellent procedural success for the Virtue sirolimus-eluting angioplasty balloon, 6-month LLL rates in line with current stent-free ISR treatment options, and clinical outcomes that warrant further evaluation in dedicated randomized studies.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Equipment Design; Europe; Feasibility Studies; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Sirolimus; Stents; Time Factors; Treatment Outcome

It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.

Topics: Aged; Antineoplastic Agents; Cilostazol; Coronary Angiography; Coronary Restenosis; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Sirolimus; Tetrazoles

To investigate the impact of sex on clinical outcomes after drug-eluting stent (DES) implantation in real-world patients.. A total number of 4720 patients (3365 males and 1355 females) undergoing the second-generation cobalt-chromium sirolimus-eluting stent (CoCr-SES) implantation from the FOCUS registry were included in this analysis. The cumulative incidences of major adverse cardiovascular event (MACE) (1.5% vs. 2.4%; p = .03), cardiovascular death (0.5% vs. 1.0%; p = .02) and target vessel revascularization (TVR) (0.3% vs. 0.8%; p = .01) within six months were significantly higher in females and the risks of MACE (adjusted hazard ratio [HR] 0.5 (0.3-0.9); p = .01) and TVR (adjusted HR 0.1(0.0-0.5); p = .001) remained significant in multivariate analysis. Reversely, the cumulative incidences of MACE (5.4% vs. 4.8%; p = .04) and any revascularization (5.1% vs. 3.3%; p = .01) were significantly higher in males beyond six months and the risks of all-cause death (adjusted HR 1.6 (1.1-2.5); p = .03) and cardiovascular death (adjusted HR 1.9 (1.1-3.6); p = .03) turned out to be significant in multivariate analysis. Notes: All cumulative incidences were presented as male vs. female; all HRs were calculated as male relative to female.. Females were associated with higher risk of early adverse events, while, males were associated with higher risk of late adverse events. Key messages Females undergoing PCI are typically older, have more cardiovascular risk factors, while, males in need of PCI are more frequently associated with complex lesions. The overall three-year cumulative incidences of adverse events are not significantly different between males and females but numerically higher in males. Females are associated with significantly higher risks of MACE and TVR within six months, while, males are associated with significantly higher risk of all-cause mortality and cardiac mortality beyond 6 months.

Topics: Aged; Asia, Southeastern; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Registries; Risk Factors; Sex Factors; Sirolimus; Thrombosis; Treatment Outcome

Our aim was to assess the safety and efficacy of paclitaxel-eluting balloon (PTX-B) treatment after bare metal stent (BMS) implantation in patients undergoing primary angioplasty.. After BMS implantation, patients were randomised (1:1) to treatment with a PTX-B or no PTX-B treatment (BMS group). The primary endpoint was in-stent late luminal loss (LLL) at nine-month follow-up. OCT was carried out on the first 20% of consecutive patients included in the study. Two hundred and twenty-three patients were randomised (BMS: 112, PTX-B: 111). At nine months, median LLL was 0.80 mm (interquartile range [IQR] 0.36-1.26) in the BMS group vs. 0.31 mm (IQR 0.00-0.58) in the PTX-B group, p<0.0001. Binary restenosis was significantly lower in the PTX-B group: 29.8% vs. 2.2%, p<0.0001, 95% confidence interval (CI): 3.2-54.2. Nine-month OCT showed good strut coverage in both groups but greater in the BMS group (100±0.0% vs. 99.52±1.11%, p=0.03) with very low rates of malapposed struts per lesion. One-year MACE was significantly lower in the PTX-B group (12.5% vs. 3.6%, p=0.016).. PTX-B after successful BMS implantation resulted in less LLL and better clinical outcomes as compared with a BMS-only strategy. This was associated with good stent strut coverage and very low rates of malapposed struts.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Metals; Middle Aged; Myocardial Infarction; Paclitaxel; Sirolimus; Treatment Outcome; Young Adult

The aim of this study was to investigate the efficacy and safety of the hybrid ultrathin-strut sirolimus-eluting stent (SES) with biodegradable polymer compared with the thin-strut everolimus-eluting stent (EES) with durable polymer in successfully recanalized chronic total occlusions (CTOs).. The introduction of drug-eluting stents revolutionized the treatment of CTOs. However, limited data are available on new-generation drug-eluting stents with biodegradable polymer in CTOs.. In this multicenter trial, patients were randomized, after successful CTO recanalization, to either SES or EES. The primary noninferiority endpoint was in-segment late lumen loss (noninferiority margin 0.2 mm). Secondary endpoints included in-stent late lumen loss and clinical endpoints.. Overall, 330 patients were included. At 9 months, angiography was available in 281 patients (85%). Duration of occlusion ≥3 months was 92.5%, with mean stent length of 52.4 ± 28.1 mm versus 52.3 ± 26.5 mm in the SES and EES groups. The primary noninferiority endpoint, in-segment late lumen loss, was not met for SES versus EES (0.13 ± 0.63 mm vs. 0.02 ± 0.47 mm; p = 0.08, 2-sided; difference 0.11 mm; 95% confidence interval: -0.01 to 0.25 mm; p. This randomized trial failed to show noninferiority of hybrid SES relative to EES in terms of in-segment late lumen loss in successfully recanalized CTOs. Furthermore, a statistically significantly higher rate of binary restenosis was found with SES.

Topics: Absorbable Implants; Aged; Belgium; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Netherlands; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

This study sought to assess the safety and effectiveness of the drug-filled stent (DFS) (Medtronic, Santa Rosa, California) in the treatment of patients with coronary artery disease.. Polymer-free drug-eluting stents have the potential to improve clinical outcomes and facilitate shorter durations of dual antiplatelet therapy. The polymer-free DFS is made from a trilayered continuous wire with an outer cobalt chromium layer, a middle tantalum layer, and an inner lumen coated with sirolimus. Small laser-drilled holes on the abluminal stent surface control drug elution.. The RevElution trial enrolled 100 patients with de novo coronary lesions 2.25 to 3.50 mm in diameter and length ≤27 mm in 2 cohorts of 50 patients for angiographic, intravascular ultrasound, and clinical assessment at 9 or 24 months, with optical coherence tomography performed in a subset of 30 patients at each time period. The primary endpoint was angiographic in-stent late lumen loss at 9 months compared with Resolute zotarolimus-eluting stent (Medtronic) historical control data.. Fifty patients with 56 lesions were treated with DFS in the 9-month cohort. In-stent late lumen loss was 0.26 ± 0.28 mm for DFS and 0.36 ± 0.52 mm for Resolute (p. At 9 months, the polymer-free DFS was safe and effective with high rates of early strut coverage and noninferior late lumen loss compared to Resolute. (Medtronic RevElution Trial [RevElution]; NCT02480348).

Topics: Australia; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Latin America; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prosthesis Design; Risk Factors; Singapore; Sirolimus; Tantalum; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

We performed a randomised controlled open-label non-inferiority trial to compare angiographic outcomes between the ultra-thin strut, biodegradable hybrid polymer Orsiro sirolimus-eluting stent (O-SES) and the durable biocompatible polymer Resolute Integrity zotarolimus-eluting stent (R-ZES).. A total of 372 patients planned to undergo percutaneous coronary revascularisation were randomly assigned 2:1 to treatment with O-SES or R-ZES (250 and 122 patients, respectively). O-SES was non-inferior to R-ZES for the primary endpoint, in-stent late lumen loss at nine months (median 0.06 mm [interquartile range, -0.09 to 0.24 mm] versus 0.12 mm [-0.07 to 0.32 mm]; p for non-inferiority <0.001; p for superiority=0.205). Percent diameter stenosis was significantly lower in the O-SES group than in the R-ZES group (15.0 [10.0 to 20.0] versus 20.0 [13.3 to 26.0]; p=0.002). Target lesion failure occurred in 2.4% and 3.3% of the O-SES and R-ZES groups, respectively (p=0.621). Subgroup analyses showed consistently similar outcomes between the two groups in terms of the primary endpoint, except for the diabetic subgroup.. O-SES was non-inferior to R-ZES in terms of in-stent late loss at nine months. Angiographic restenosis and clinical adverse events were low in both groups. This study confirms the good safety and efficacy profiles of both contemporary coronary stents.

Topics: Adult; Aged; Aged, 80 and over; Coronary Angiography; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Polymers; Sirolimus; Treatment Outcome

First-generation drug-eluting coronary stents (DES) were introduced in 2003 to 2004, and their use resulted in a considerable reduction in the development of in-stent restenosis at the cost of an increased risk of late stent thromboses.. This study followed clinical outcomes of patients included in a large randomized trial for 10 years to enable detection of late changes in annual event rates that could necessitate medical attention.. A total of 2,098 unselected all-comer patients (50% with acute coronary syndrome) were randomly assigned to have a first-generation DES implanted. This study recorded the occurrence of a major adverse cardiac event (MACE) assessed as the composite of cardiac death, myocardial infarction, and target vessel revascularization. Stent thromboses were also assessed.. Of the 2,098 unselected patients, 73.1% were still alive after 10 years. During the follow-up period, MACE occurred in 346 (32.5%) in the group receiving a sirolimus-eluting stent and in 342 (33.1%) in the group receiving a paclitaxel-eluting stent (hazard ratio: 0.96; 95% confidence interval: 0.83 to 1.11; p = 0.60), with a steady annual rate of 2.6% after the first year. Definite, probable, and possible stent thrombosis appeared in 279 patients (13.3%), with no difference between stent types and with a steady annual rate of 1.3% after the first year.. Among the surviving patients, the long-term annual MACE rate and the stent thrombosis rate appeared constant for both stent types, with no apparent late changes. Although there is no need for extraordinary medical attention for these patients, the absence of declines in annual event rates calls for continuous surveillance. (Danish Organization on Randomized Trials With Clinical Outcome II [SORT OUT II]; NCT00388934).

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Time Factors; Treatment Outcome

Previous studies have suggested a benefit of cilostazol in addition to standard dual-antiplatelet therapy (DAPT), reducing in-stent late luminal loss and restenosis after percutaneous coronary intervention (PCI) with bare-metal and drug-eluting stent (DES) implantation. However, there is a paucity of intravascular ultrasound (IVUS) assessment of neointimal tissue hyperplasia (NIH) after triple-antiplatelet therapy (TAPT), especially in diabetic patients treated with DES.. This prospective, placebo-controlled trial was conducted in diabetic patients randomized (1:1) to receive either standard DAPT (aspirin and clopidogrel) vs TAPT with cilostazol for a minimum of 12 months after PCI with Endeavor zotarolimus-eluting stent (E-ZES). The primary endpoint was the 9-month comparison of percentage of NIH in both groups. Additionally, we compared in-stent late lumen loss, binary restenosis, major adverse cardiac event (MACE; cardiac death, non-fatal myocardial infarction, and restenosis) rates, and the incidence of vascular/bleeding complications.. In total, 133 diabetic patients were enrolled (cilostazol cohort = 65 patients) with 56.4% male and mean age of 60.8 years. Overall, the two cohorts were comparable in terms of baseline clinical and angiographic characteristics, except for the reference vessel diameter, which was smaller among patients randomized to cilostazol (2.48 ± 0.46 mm vs 2.69 ± 0.48 mm; P=.01). At 9 months, there was a non-significant trend toward less percentage of NIH obstruction in the TAPT cohort (33.2 ± 8.29% vs 35.1 ± 8.45%; P=.07). However, this finding did not impact angiographic late-lumen loss (0.60 ± 0.46 mm cilostazol group vs 0.64 ± 0.48 mm control group; P=.30) and binary restenosis (9.8% vs 6.8%; P=.99). MACE rate also did not significantly differ between the cohorts (13.8% cilostazol group vs 8.8% control group; P=.81). Of note, the addition of a third antiplatelet agent did not increase vascular and bleeding complications.. In diabetic patients treated with E-ZES, TAPT with cilostazol did not add any significant benefit in terms of NIH suppression or MACE reduction.

Topics: Aspirin; Cilostazol; Clopidogrel; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Sirolimus; Tetrazoles; Ticlopidine; Treatment Outcome

Incomplete neointimal coverage and malapposed struts after stenting are associated with increased risk of stent thrombosis. We aimed to evaluate neointimal coverage early after Resolute zotarolimus-eluting stent (R-ZES) implantation using optical coherence tomography (OCT). A total of 20 patients with de novo native coronary lesions with R-ZES were enrolled. Among these patients, 20 stented lesions in 19 patients were evaluated at 1, 2, and 3 months after R-ZES implantation. The strut apposition and neointimal coverage were evaluated by OCT. Neointimal hyperplasia (NIH) thickness and percentage of covered struts and the proportion of incompletely apposed struts were measured at 1-mm intervals. The mean percentages of covered stent struts were over 85 % within 3 months (88.4 ± 6.3 % at 1 month, 95.5 ± 5.5 % at 2 months, 93.6 ± 3.5 % at 3 months). The percentages of incompletely apposed struts were not significantly different among the groups (4.4 ± 4.2 % at 1 month, 1.9 ± 1.9 % at 2 months, 3.1 ± 2.2 % at 3 months, p = 0.51). Mean NIH thickness (38.9 ± 8.1 μm at 1 month, 70.6 ± 18.8 μm at 2 months, 54.1 ± 5.9 at 3 months, p = 0.0016) was thickest in the 2 months group. Most of all OCT findings within 2 months demonstrated neointimal coverage with low signal intensity. The neointimal coverage of ZES-R was over 85 % within 3 months. These data may support shorter requirement of dual antiplatelet therapy duration with R-ZES.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

We aimed to compare healing responses with optical coherence tomography, and clinical and angiographic outcome after treatment of coronary bifurcation lesions with a dedicated stent versus a conventional culotte technique.. Forty patients with true and complex coronary bifurcation lesions were randomly assigned to treatment with the Axxess™ bifurcation stent in the proximal main vessel (MV) and additional BioMatrix™ stents in the branches (Biosensors Europe SA, Morges, Switzerland), versus a culotte technique using XIENCE™ stents (Abbott Vascular, Santa Clara, CA, USA). The primary endpoint of percentage of uncovered struts at nine months was similar with the dedicated strategy vs. culotte in the proximal MV (median 17.8 [IQR 3.3-24.7] vs. 6.8 [2.0-20.5]; p=0.19), bifurcation core (9.5 [5.7-19.5] vs. 4.0 [0.7-17.6]; p=0.17), distal MV (2.6 [2.3-18] vs. 2.2 [0.5-6.0]; p=0.09) and side branch (5.7 [1.5-11.5] vs. 1.9 [0-5.8]; p=0.14). As compared with culotte, a strategy using Axxess resulted in a significantly larger lumen in the proximal MV both acutely (minimum lumen diameter 3.03±0.51 vs. 2.71±0.44 mm, p=0.04) and at follow-up (mean lumen area 10.0±2.1 vs. 7.1±1.8 mm2, p<0.001), and in a lower angiographic late lumen loss (p=0.05). Both strategies resulted in good clinical outcomes at one year, and no stent thromboses.. As compared with a culotte strategy with XIENCE stents, complex bifurcation stenting using a dedicated strategy combining Axxess and BioMatrix stents results in similar stent strut coverage at nine-month follow-up, and a significantly larger lumen and lower angiographic late lumen loss in the proximal MV.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome

To compare the incidence and predictors of target lesion revascularisation (TLR) and non-TLR after percutaneous coronary intervention with drug-eluting stents (DES).. We pooled patient-level data on 6,137 patients (Resolute zotarolimus-eluting stent: 5,016, XIENCE everolimus-eluting stent: 1,121) in the RESOLUTE Global Program. At three years, clinically driven TLR, unplanned non-TLR, and no revascularisation occurred in 186, 618, and 5,333 patients, respectively. On multivariate analysis, predictors of both TLR and non-TLR were pre-procedure diameter stenosis (%) (odds ratio [OR] 1.01, 95% confidence interval [CI] [1.01-1.02], and OR 0.99 [0.99-1.00]), diabetes (OR 1.46 [1.07-1.99], and OR 1.37 [1.15-1.64]), and prior PCI (OR 1.42 [1.01-2.00], and OR 1.41 [1.18-1.68]). Baseline characteristics associated with TLR only were prior coronary artery bypass graft surgery (OR 2.85 [1.91-4.27]), in-stent restenosis (OR 2.35 [1.43-3.83]), age (OR 0.98 per year [0.97-1.00]), hypertension (OR 1.64 [1.10-2.44]), and pre-procedure reference vessel diameter (OR 0.74 per mm [0.55-0.99]). Baseline characteristics associated with non-TLR only were lesion location (left anterior descending vs. all others) (OR 0.70 [0.59-0.83]), and hyperlipidaemia (OR 1.42 [1.15-1.75]).. The cumulative incidence of non-TLR at three years in patients treated with current-generation DES was almost three times higher than TLR.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM).. The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM.. This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up.. A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group.. AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Spain; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Head-to-head optical coherence tomography (OCT) data comparing metallic stents with bioresorbable vascular scaffolds (BVS) are lacking. This study assessed vascular healing at 9-month follow-up after implantation of everolimus- and biolimus-eluting stents (EES; BES) and everolimus-eluting BVS.. OCT was performed in 74 patients enrolled in the EVERBIO II (NCT01711931) trial (23 with EES: 26 lesions, 7 625 struts; 23 with BES: 26 lesions, 6 140 struts; 28 with BVS: 33 lesions, 10 891 struts). OCT images were acquired using the pullback and nonocclusive flushing technique and analysed offline.. BVS demonstrated fewer uncovered struts per patient (12 ± 27 [3.8 ± 8.4%] vs 59 ± 55 [21.8 ± 13.7%] in the EES&BES group, p <0.001), and thicker neointimal hyperplasia (BVS 102 ± 44 µm vs EES&BES 66 ± 36 µm, p <0.01). There was no significant difference with regard to malapposed struts (2.1 ± 2.7% in the BVS vs 4.4 ± 8.8% in the EES&BES group, p = 0.41). In a predefined signal intensity scale, quantitative analysis of the "key component" (black) revealed lower intensity in BVS than EES&BES (14 ± 23% vs 13 ± 12%, p = 0.007). Intensity was lower in polylactide-containing stents (BVS&BES) than in EES (15 ± 19% vs 10 ± 10%, p <0.001).. BVS has fewer uncovered struts and presents with a thicker neointimal coverage compared with EES&BES. It is not known whether this improved capping correlates with superior vascular healing. Polylactide-containing stents (BVS and BES) demonstrate lower peristrut intensity compared with EES.

Topics: Absorbable Implants; Aged; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Single-Blind Method; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome

This registry evaluated the safety and clinical outcomes of the Combo stent in an all-comers population in routine clinical practice. We report 1-year results.. Limitations of current generation drug-eluting stents (DES) are 3-fold: stent thrombosis, neoatherosclerosis related to impaired healing, and repeat revascularization due to (late-) in-stent restenosis. The Combo stent combines an abluminal biodegradable coating eluting sirolimus and a luminal anti-CD34(+) antibody layer to attract endothelial progenitor cells in order to promote vessel healing, thus preventing neointima formation and restenosis.. The REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) post-market registry was an international, multicenter, prospective trial that evaluated clinical outcomes after deployment of the Combo stent, in an all-comers population of patients treated with a Combo stent in the setting of routine clinical care. Clinical endpoints were target lesion failure (TLF), defined as a composite of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR).. Between June 2013 and March 2014, a total of 1,000 patients were included in the registry, 49.9% of whom presented with acute coronary syndrome. Mean age was 65 ± 11 years old (range: 34 to 94 years of age), and 74% of patients were male; 58.9% of 1,255 lesions were American Heart Association type B2 or C lesions. The primary endpoints were 5.7% TLF, 1.7% cardiac death, 0.7% target vessel MI, and 4.4% TLR. Definite stent thrombosis occurred in 0.5% of subjects; no thrombosis occurred after 9 days post-stenting.. This registry showed excellent 1-year results of novel Combo bioengineered stent technology in an all-comers patient population. (Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE]; NCT01874002).

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Europe; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Product Surveillance, Postmarketing; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Wound Healing

Bioresorbable scaffolds were designed to overcome the limitations of permanent stents. In the BIOSOLVE-I study we aimed to assess the long-term safety and performance of a drug-eluting absorbable metal scaffold (DREAMS) at three years.. In this prospective, multicentre first-in-man study, 46 patients with 47 de novo lesions were enrolled. We report the final results at three-year follow-up. Mean age was 65.3±9.7 years, lesions were 2.73±0.48 mm in diameter and 10.99±4.59 mm long. Follow-up at three years was available for 44 patients (one patient died of a non-cardiac cause and one patient withdrew consent). Three target lesion failures (TLF) occurred (6.6%), consisting of two clinically driven target lesion revascularisations at scheduled six-month angiography (4.3%) and one myocardial infarction after drug-eluting balloon treatment in a non-target lesion but target vessel at 12-month angiography (2.2%). No cardiac death or scaffold thrombosis occurred. Seven patients had additional angiographic follow-up at 28±4 months: in-scaffold late lumen loss had improved from 0.51±0.46 mm (median 0.28 mm) at 12 months to 0.32±0.32 mm (median 0.20 mm).. The BIOSOLVE-I study showed excellent long-term outcomes at three years with a low TLF rate and no cardiac death or scaffold thrombosis. No TLF event was observed beyond 377 days.

Topics: Absorbable Implants; Adult; Aged; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Tissue Scaffolds

Current monotherapy drug-eluting stents are associated with impaired healing, neoatherosclerosis, and late stent thrombosis. The healing profile and neointimal transformation of the first dual-therapy endothelial progenitor cell-capturing sirolimus-eluting stent are unknown.. In this prospective, single-center study, 61 patients treated with the Combo stent had optical coherence tomography at baseline, early follow-up (4 monthly groups in a 1:2:2:1 ratio from 2 to 5 months), 9 months, and 24 months. Optical coherence tomography early strut coverage increased from 77.1% to 92.5% to 92.7% to 94.9% between 2 and 5 months. At 9 months, the major adverse cardiac event rate was 1.64%, and angiographic in-stent late loss was 0.24 mm (0.08-0.40). The 36-month major adverse cardiac event rate was 3.3%. From 9 to 24 months, neointimal regression was confirmed by optical coherence tomography: neointimal thickness (median [first quartile and third quartile]), 0.14 mm (0.08 and 0.21) versus 0.12 mm (0.07 and 0.19), P<0.001; neointimal volume, 29.9 mm(3) (22.1 and 43.2) versus 26.2 mm(3) (19.6 and 35.8), P=0.003; and percent neointimal volume, 17.8% (12.2 and 21.2) versus 15.7% (11.2 and 19.4), P=0.01. No definite or probable late stent thrombosis was recorded.. With additional endothelial progenitor cell-capturing technology, the Combo stent exhibits a unique late neointimal regression (from 9 to 24 months) that has not been reported in any drug-eluting stents, translating into good 36-month clinical results with minimal restenosis and no late stent thrombosis. This is the first study testing the concept of using a longitudinal sequential optical coherence tomography protocol to continuously document early healing profile and late neointimal transformation, predicting long-term outcomes of a new novel stent platform.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01274234, NCT01756807, and NCT02263313.

Topics: Aged; Cardiovascular Agents; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Endothelial Progenitor Cells; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

In percutaneous coronary intervention for de-novo coronary bifurcation lesions, the optimal technique for provisional side-branch stenting is still a matter of debate. We tested whether in this setting culotte stenting reduces the incidence of restenosis as compared with T-and-protrusion (TAP) stenting.. This trial included 300 patients with a coronary bifurcation lesion requiring a side-branch stent. Patients were randomly assigned to culotte stenting or TAP stenting using drug-eluting stents in a 1:1 fashion. Primary endpoint was maximal per cent diameter stenosis of the bifurcation lesion at 9-month angiographic follow-up. As clinical endpoints we assessed target lesion re-intervention (TLR) and target lesion failure (composite of cardiac death, target vessel myocardial infarction, and TLR).Angiographic follow-up was available in 91% of the patients. After culotte stenting, the maximum per cent diameter stenosis in the treated bifurcation lesion was 21 ± 20% as compared with 27 ± 25% after TAP stenting (P = 0.038). The respective corresponding binary restenosis rates were 6.5 and 17% (P = 0.006). The 1-year incidence of TLR was 6.0% after culotte stenting vs. 12.0% after T-stenting (P = 0.069). Target lesion failure occurred in 6.7% of the culotte group and in 12.0% of the TAP group (P = 0.11). Only one patient of the culotte group incurred a definite stent thrombosis during 1-year follow-up.. Compared with the TAP stenting, culotte stenting was associated with a significantly lower incidence of angiographic restenosis.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus; Treatment Outcome

Compared with bare metal stents, first-generation drug-eluting stents (DES) are associated with an increased risk of late restenosis and stent thrombosis (ST). Whether this risk continues or attenuates during long-term follow-up remains unknown.. We extended the follow-up of 1012 patients [sirolimus-eluting stent (SES): N = 503 and paclitaxel-eluting stent (PES): N = 509] included in the all-comers, randomized Sirolimus-Eluting vs. Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) trial to 10 years. Follow-up was complete in 895 patients (88.4%) at 10 years. At 1, 5, and 10 years of follow-up, rates of ischaemia-driven target lesion revascularization (ID-TLR) were 8.1%, 14.6% and 17.7%, respectively, and rates of ST were 1.9%, 4.5% and 5.6%, respectively. The annual risks of ID-TLR and definite ST were significantly higher between 1 and 5 years as compared with the 5- to 10-year period [ID-TLR: 1.8% vs. 0.7%/year, hazard ratio (HR) 0.36, 95% confidence intervals (95% CI) 0.21-0.62, P < 0.001; definite ST: 0.67% vs. 0.23%/year, HR 0.31, 95% CI 0.13-0.75, P = 0.01]. The attenuation of the risk of ID-TLR and ST beyond 5 years was independent of age. Major adverse events (cardiac death, myocardial infarction, and ID-TLR) occurred in 33.7% of SES- and 33.8% of PES-treated patients (P = 0.72).. During long-term follow-up through 10 years, the annual risks of ID-TLR and definite ST significantly decreased beyond 5 years after first-generation DES implantation. These findings may have important implications for secondary prevention after percutaneous coronary intervention with first-generation DES including long-term antiplatelet therapy.. http://www.clinicaltrials.gov. Unique identifier: NCT00297661.

Topics: Coronary Restenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Myocardial Infarction; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Improved outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention remain an unmet clinical need. We assessed the long-term efficacy and safety of novel polymer-free sirolimus- and probucol-eluting stent in diabetic patients enrolled in intracoronary stenting and angiographic results: test efficacy of sirolimus- and probucol-eluting versus zotarolimus-eluting stents 5 trial.. In a pre-specified subgroup analysis, outcomes of diabetic patients treated with a sirolimus- and probucol-eluting stent or a second-generation zotarolimus-eluting stent were compared. The primary endpoint was a device-oriented composite outcome comprising cardiac death, target vessel-related myocardial infarction (MI), or target lesion revascularization (TLR) at 5-year follow-up. Event-free survival was assessed using the Kaplan-Meier method. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated from univariate Cox proportional hazards models.. A total of 870 patients with diabetes mellitus were treated with either a sirolimus- and probucol-eluting stent (n = 575) or a second-generation zotarolimus-eluting stent (n = 295). At 5 years, the rate of device-oriented composite endpoint was comparable between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent (32.9 versus 33.4 %, HR 0.88, 95 % CI 0.76-1.26). No significant differences were observed between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent groups in the incidence of cardiac death (15.6 versus 16.7 % HR 0.92, 95 % CI 0.63-1.32), target-vessel MI (4.6 versus 6.6 %, HR 0.73, 95 % CI 0.40-1.34), and TLR (18.6 versus 18.8 %, HR 1.00, 95 % CI, 0.72-1.41). The rate of definite or probable stent thrombosis was low and similar in both groups (2.5 versus 2.6 %, HR 1.02, 95 % CI, 0.41-2.52).. In patients with diabetes the long-term efficacy and safety of a polymer-free sirolimus- and probucol-eluting stent were comparable to a second-generation durable polymer zotarolimus-eluting stent. Trial registration ClinicalTrials.gov NCT00598533. Registered 10 January 2008.

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Diabetic Angiopathies; Disease-Free Survival; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Probucol; Proportional Hazards Models; Prosthesis Design; Retreatment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The biodegradable polymer drug-eluting stents (DES) were developed to improve vascular healing. However, further data and longer-term follow-up are needed to confirm safety and efficacy of these stents. This randomized clinical trial aimed to compare safety and efficacy of 2 sirolimus-eluting stents (SES): Cordimax-a novel abluminal biodegradable polymer SES and Cypher Select-a durable polymer SES, at 9 months angiographic and 5-year clinical follow-up.. We randomized 402 patients with coronary artery disease to percutaneous coronary intervention with Cordimax (n = 202) or Cypher select (n = 200). Angiographic follow-up was performed at 9 months after the index procedure and clinical follow-up annually up to 5 years. The primary endpoint was angiographic in-stent late luminal loss (LLL). Secondary endpoints included angiographic restenosis rate, target vessel revascularization (TVR), and major adverse cardiac events (MACEs; defined as cardiac death, myocardial infarction, or TVR) at 5-year follow-up.. Cordimax was noninferior to Cypher select for in-stent LLL (0.25 ± 0.47 vs 0.18 ± 0.49 mm; P = 0.587) and in-stent mean diameter stenosis (22.19 ± 12.21% vs 19.89 ± 10.79%; P = 0.064) at 9 months angiographic follow-up. The MACE rates were not different at 1 year (5.9% vs 4.0%, P = 0.376); however, MACE rates from 2 to 5 years were lower in the Cordimax group (6.8% vs 13.1%; P = 0.039).. Abluminal biodegradable polymer SES is noninferior to durable polymer SES at 9-month angiographic and 1-year clinical follow-up. However, MACE rates from 2 to 5 years were less in the abluminal biodegradable polymer group.

Topics: Absorbable Implants; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Durable Medical Equipment; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Polymers; Postoperative Complications; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

To compare the efficacy and safety of the MiStent absorbable polymer sirolimus-eluting stent (APSES) with a zotarolimus-eluting stent (ZES).. The trial was a 2:1 randomisation at 26 sites of 184 patients implanted with an APSES (n=123) versus a ZES (n=61). Following stent implantation, all patients underwent quantitative coronary angiography at baseline and at nine months of follow-up, while a select subgroup also underwent optical coherence tomography (OCT). The primary efficacy hypothesis was superiority of in-stent late lumen loss (LLL) of APSES compared to ZES. At nine months, the primary endpoint was met, with a mean in-stent LLL of 0.27±0.46 mm in 103 APSES patients versus 0.58±0.41 mm in 52 ZES patients (p<0.001). The proportion of uncovered stent struts by OCT at nine months was very low in both groups. The mean neointimal thickness of covered struts (p=0.002) and percent net volume obstruction (p≤0.003) were significantly lower in the APSES than in the ZES group. Major adverse cardiac event and stent thrombosis rates were low and comparable between groups.. The DESSOLVE II trial demonstrated superiority in the primary efficacy endpoint of nine-month mean LLL for APSES compared to ZES. Strut coverage by OCT was high with both stents and the clinical safety endpoints including stent thrombosis were equally low in both groups. ClinicalTrials.gov Identifier: NCT01294748.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Single-Blind Method; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

The Japan drug-eluting stents evaluation: a randomized trial (J-DESsERT) was conducted to compare the effectiveness of 2 different drug-eluting stents (DES). It remains uncertain which is more efficacious in diabetic patients, sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES). In this trial, the largest of its kind, 3,533 patients including 1,724 diabetes mellitus (DM) patients were randomized to either SES or PES. Stratification was based on the presence or absence of DM. PES target vessel failure (TVF) non-inferiority at 8 months (primary endpoint) was not demonstrated when compared to SES (SES 4.5 % vs. PES 6.4 %, p = 0.23). In addition, PES TVF superiority at 8 months in the DM subset (secondary endpoint) was not shown (SES 5.6 % vs. PES 7.6 %, p = 0.10). Insulin treatment was associated with increased TVF rates, however, this was less pronounced in the PES group. At 8 months, the similar TVF rates for SES and PES up to that point diverged significantly, favoring SES out to 12 months. Patients undergoing routine angiographic follow-up demonstrated lower TVF prior to the 8-month point, and higher TVF after 8 months, as compared to those followed clinically. In conclusion, the current study failed to demonstrate the proposed superiority of PES for DM patients. In addition, the diversion of TVF at 8 months may reflect an "oculo-stenotic reflex" bias (the tendency to treat lesions found during routine, rather than clinically driven, angiographic follow-up), which could constitute an obstacle for evaluating the true clinical effect of new devices.

Topics: Aged; Anti-Bacterial Agents; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Paclitaxel; Sirolimus; Treatment Outcome; Tubulin Modulators

Sirolimus-eluting stents (SES) have been shown to be superior to Endeavor zotarolimus-eluting stents (ZES) and comparable to Resolute ZES at eight-month angiography in patients treated for total coronary occlusions (TCO). This study investigated clinical outcome at three-year follow-up.. The PRISON III trial investigated the efficacy and safety of SES against ZES (Endeavor and Resolute) in two study phases. In the first phase, 51 patients were randomised to receive SES and 46 to Endeavor ZES. In the second phase, 103 and 104 patients were randomised to SES or Resolute ZES, respectively. Between one and three years there were only a few additional clinical events in all groups. As a result, the rates of target lesion revascularisation 12.2% vs. 19.6%, p=0.49, target vessel failure 14.3% vs. 19.6%, p=0.68, and definite or probable stent thrombosis 4.1% vs. 2.2% were comparable between SES and Endeavor ZES at three years. In the second study phase, the rates of target lesion revascularisation 10% vs. 5.9%, p=0.42, target vessel failure 10% vs. 7.9%, p=0.79 and definite or probable stent thrombosis 1.0% vs. 0% were similar between SES and Resolute ZES.. The present study demonstrated a low incidence of clinical events between one- and three-year follow-up with either SES compared to Endeavor ZES or SES versus Resolute ZES in patients treated for total coronary occlusions.

Topics: Aged; Antibiotics, Antineoplastic; Cardiovascular Diseases; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Reoperation; Sirolimus; Thrombosis

The aim of this study was to evaluate the extent of neointimal response after the implantation of a second-generation drug-eluting stent, zotarolimus-eluting stent (ZES-ER, Endeavor Resolute) or everolimus-eluting stent (EES, Xience V), using intravascular ultrasound (IVUS) in diabetic patients.. In all, 154 diabetic patients with de-novo coronary lesions were randomized to be implanted with a ZES-ER or EES, and the angiographic follow-up at 9 months combined with a complete IVUS study was available for 96 patients with 101 lesions.. Baseline demographic and lesion parameters were similar in both groups at index percutaneous coronary intervention. On follow-up angiography, in-stent late lumen loss and minimal lumen diameter were not different between the two groups. On IVUS study, neointimal hyperplasia volume [median (interquartile range): ZES-ER vs. EES; 2.25 mm (0.57-6.25) vs. 1.59 mm (0.45-8.37), P=0.615] and in-stent percentage of volume obstruction [median (interquartile range): ZES-ER vs. EES; 1.16% (0.33-3.61) vs. 0.77% (0.29-4.01), P=0.615] showed similar results between the two groups.. In diabetic patients, the second-generation drug-eluting stents, ZES-ER and EES, were comparable in inhibiting neointimal proliferation.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Pilot Projects; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS).. This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients.. A multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting.. A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]).. Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020).

Topics: Aged; Aspirin; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Early Termination of Clinical Trials; Europe; Everolimus; Female; Hemorrhage; Humans; Immunosuppressive Agents; Male; Middle Aged; Middle East; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Sirolimus; Ticlopidine; Time Factors; Treatment Outcome

We compared 5-year clinical outcomes in diabetic and nondiabetic patients treated with Endeavor zotarolimus-eluting stents (ZESs; Endeavor Sprint, Medtronic, Santa Rosa, California) or Cypher sirolimus-eluting stents (SESs; Cordis, Johnson & Johnson, Warren, New Jersey) coronary implantation. We randomized 2,332 patients to either ZESs (n = 1,162, n = 169 diabetic patients) or SESs (n = 1,170, n = 168 diabetic patients) stratified according to presence or absence of diabetes mellitus. End points included major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, target vessel revascularization (TVR), and definite stent thrombosis. Among diabetic patients, MACE occurred more frequently in patients treated with ZESs than SESs (48 [28.4%] vs 31 [18.5%]; odds ratio [OR] 1.75, 95% confidence interval [CI] 1.05 to 2.93, p = 0.032) because of a higher rate of TVR (32 [18.9%] vs 14 [8.3%]; OR 2.57, 95% CI 1.32 to 5.02, p = 0.006). Among nondiabetic patients, ZES and SES had similar MACE rates at 5-year follow-up but SES was associated with a significantly higher risk of definite stent thrombosis (10 [1.0%] vs 23 [2.3%]; OR 0.43, 95% CI 0.20 to 0.91, p = 0.028). Moreover, during the last 4 years, ZES had fewer MACE, TVR, and stent thrombosis events among nondiabetic patients. In conclusion, SES remains superior to ZES in patients with diabetes throughout the 5-year follow-up, however, among nondiabetic patients, SES demonstrated a highly dynamic performance with favorable initial results followed by a late catch-up that included an overall higher risk of stent thrombosis.

Topics: Blood Vessel Prosthesis Implantation; Case-Control Studies; Coronary Artery Disease; Coronary Restenosis; Diabetes Complications; Diabetes Mellitus; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Male; Myocardial Infarction; Prosthesis Failure; Reoperation; Sirolimus; Thrombosis; Treatment Outcome

Stents with a passive coating of titanium-nitride-oxide (TiNO) have been compared with Endeavor® zotarolimus-eluting stents (E-ZES) with regard to the primary endpoint of in-stent late lumen loss at six to eight months. The objective of the present analysis was to compare the long-term outcomes of TiNO stents with E-ZES up to five years of clinical follow-up.. A total of 302 patients had been randomly allocated to treatment with TiNO or E-ZES. Up to five years of follow-up, major adverse cardiac events (MACE), the composite of cardiac death, myocardial infarction, or clinically indicated target vessel revascularisation (TLR), were observed in 27.6% of patients treated with TiNO stents and 25.3% of patients treated with E-ZES (RR 1.13, 95% CI: 0.72-1.75, p=0.60), with the majority of events related to clinically indicated TVR (TiNO 21.7% versus E-ZES 20.7%, RR 1.10, 95% CI: 0.67-1.81). There were no differences with respect to individual events including cardiac death, myocardial infarction or stent thrombosis between the two treatment arms up to five years of follow-up. A majority of patients remained free from angina throughout the entire study duration (TiNO 77.3% versus E-ZES 76.1%, p=0.92).. Final five-year outcomes of the TIDE trial comparing TiNO stents with E-ZES revealed increased rates of MACE driven primarily by clinically indicated TVR. The TIDE trial is registered at ClinicalTrials.gov: NCT00492908.

Topics: Aged; Antibiotics, Antineoplastic; Cardiovascular Diseases; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Proportional Hazards Models; Reoperation; Sirolimus; Titanium; Treatment Outcome

To evaluate the preliminary safety and efficacy of the EXCEL II stent system.. Although the first biodegradable polymer drug-eluting stent (BP-DES), EXCEL, was launched nearly a decade ago, in-stent restenosis and stent thrombosis remain pertinent clinical problems in practice. A new cobalt-chromium BP-DES EXCEL II has been developed with the aim of improving stent safety and efficacy.. Forty-five patients with single de novo native coronary lesions were enrolled and randomized to two groups in a 2:1 ratio, the 4-month follow-up group (n = 30) and the 12-month follow-up group (n = 15). All patients underwent percutaneous coronary intervention (PCI) with the EXCEL II stent system. Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) were used to assess coronary vasculature at the designated 4- or 12-month follow-up. The primary outcome was major adverse cardiac events (MACE) at 30 days post-PCI.. No MACE, thrombotic events, or target lesion failure was found in the 45 patients during the 12-month follow-up. There was no significant difference (P > 0.05) between the two groups in terms of in-stent and in-segment late lumen loss (LLL). No in-stent and in-segment restenosis was found in either group. At follow-up, the ratio of >10% uncovered struts per lesion was 26.67% in the 4-month group and 0% in the 12-month group (P < 0.05). Neointimal coverage in the 12-month group was significantly better than in the 4-month group (98.58% vs. 93.51%, P < 0.01).. This first-in-man study demonstrates promising feasibility, safety, and efficacy of EXCEL II stents. These stents were found to have rapid endothelialization and low LLL rates at 4 and 12 months after implantation.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; China; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Biodegradable polymers for release of antiproliferative drugs from drug-eluting stents aim to improve vascular healing. We assessed noninferiority of a novel ultrathin strut drug-eluting stent releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) compared with the durable polymer Xience Prime everolimus-eluting stent (X-EES) in terms of the primary end point in-stent late lumen loss at 9 months.. A total of 452 patients were randomly assigned 2:1 to treatment with O-SES (298 patients, 332 lesions) or X-EES (154 patients, 173 lesions) in a multicenter, noninferiority trial. The primary end point was in-stent late loss at 9 months. O-SES was noninferior to X-EES for the primary end point (0.10±0.32 versus 0.11±0.29 mm; difference=0.00063 mm; 95% confidence interval, -0.06 to 0.07; Pnoninferiority<0.0001). Clinical outcome showed similar rates of target-lesion failure at 1 year (O-SES 6.5% versus X-EES 8.0%; hazard ratio=0.82; 95% confidence interval, 0.40-1.68; log-rank test: P=0.58) without cases of stent thrombosis. A subgroup of patients (n=55) underwent serial optical coherence tomography at 9 months, which demonstrated similar neointimal thickness among lesions allocated to O-SES and X-EES (0.10±0.04 mm versus 0.11±0.04 mm; -0.01 [-0.04, -0.01]; P=0.37). Another subgroup of patients (n=56) underwent serial intravascular ultrasound at baseline and 9 months indicating a potential difference in neointimal area at follow-up (O-SES, 0.16±0.33 mm(2) versus X-EES, 0.43±0.56 mm(2); P=0.04).. Compared with durable polymer X-EES, novel biodegradable polymer-based O-SES was found noninferior for the primary end point in-stent late lumen loss at 9 months. Clinical event rates were comparable without cases of stent thrombosis throughout 1 year of follow-up.. http://www.clinicaltrials.gov. Unique identifier: NCT01356888.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neointima; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

We aimed to compare angiographic and clinical outcomes after the implantation of everolimus-eluting (EES) and sirolimus-eluting (SES) stents in patients with diabetes.. There are limited data on long-term outcome after EES vs SES implantation in diabetic patients.. We randomized 213 patients with diabetes and coronary artery disease to EES (n = 108) or SES (n = 105) implantation. Angiographic follow-up was performed 10 months after the index procedure and all patients were followed clinically for 4 years. The primary endpoint was angiographic in-stent late luminal loss at 10-month follow-up. Secondary endpoints included angiographic restenosis rate, the need for target lesion revascularization (TLR) and major adverse cardiac events (MACE; defined as cardiac death, myocardial infarction, definite stent thrombosis, or TLR) at 4-year follow-up.. At 10-month angiographic follow-up, in-stent late lumen loss was 0.20 ± 0.53 mm and 0.11 ± 0.49 mm (P = 0.28), and angiographic restenosis rate was 3.8% and 5.2% (P = 0.72) in the EES and SES groups, respectively. At 4-year clinical follow-up, MACE had occurred in 22 (20.4%) patients in the EES group and 25 (23.8%) patients in SES group (HR 0.84, 95% CI 0.47-1.49; P = 0.55), with TLR performed in 6 (5.6%) and 10 (9.5%) patients in the two groups (HR 0.57, 95% CI 0.21-1-58; P = 0.28).. EES and SES had comparable 10-month angiographic and 4-year clinical outcomes in patients with diabetes mellitus and coronary artery disease.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Denmark; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The first CE-approved bioresorbable vascular scaffold (BVS) is effective at treating simple lesions and stable coronary artery disease, but it has yet to be assessed versus the best-in-class drug-eluting stents (DES).. This study sought to compare the performance of a BVS with that of everolimus-eluting stents (EES) and biolimus-eluting stents (BES) in all-comer patients.. The EVERBIO II (Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents II) trial was a single-center, assessor-blinded study of 240 patients randomly assigned in a 1:1:1 ratio to EES, BES, or BVS. The only exclusion criterion was a reference vessel diameter >4.0 mm, which precluded treatment with BVS. The primary endpoint was angiographic late lumen loss (LLL) at 9 months. Secondary endpoints included patient-oriented major acute coronary events (MACE) (death, myocardial infarction [MI], and any revascularization), device-oriented MACE (cardiac death, MI, and target lesion revascularization), and stent thrombosis at the 9-month clinical follow-up.. Follow-up angiography was performed in 216 patients (90.7%) at 9 months. In-stent LLL was similar between patients treated with BVS (0.28 ± 0.39 mm) and those treated with EES/BES (0.25 ± 0.36 mm; p = 0.30). Clinical outcomes were similar at 9 months: the patient-oriented MACE rate was 27% in BVS and 26% in the EES/BES group (p = 0.83) and the device-oriented MACE rate was 12% in BVS and 9% in the EES/BES group (p = 0.6).. New-generation metallic DES (EES/BES) were not superior to BVS in terms of angiographic LLL and clinical outcomes. (Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents [EVERBIO II]; NCT01711931).

Topics: Absorbable Implants; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Materials Testing; Middle Aged; Percutaneous Coronary Intervention; Postoperative Complications; Sirolimus; Tissue Scaffolds; Treatment Outcome

The use of drug-eluting stents (DES) in patients at high risk of bleeding or thrombosis has not been prospectively studied; limited data are available in patients who have a low restenosis risk.. This study sought to compare a hydrophilic polymer-based, second-generation zotarolimus-eluting stent (ZES) with a unique drug fast-release profile versus bare-metal stents (BMS) under similar durations of dual-antiplatelet therapy (DAPT).. We randomly assigned 1,606 patients with stable or unstable symptoms, and who on the basis of thrombotic bleeding or restenosis risk criteria, qualified as uncertain candidates for DES, to receive ZES or BMS. DAPT duration was on the basis of patient characteristics, rather than stent characteristics, and allowed for a personalized 1-month dual antiplatelet regimen. The primary endpoint was the risk of 1-year major adverse cardiovascular events (MACE), which included death, myocardial infarction (MI), or target vessel revascularization (TVR).. Median DAPT duration was 32 days (interquartile range [IQR]: 30 to 180 days) and did not differ between the groups. In the ZES group, 140 patients (17.5%) reached the primary endpoint, compared with 178 patients (22.1%) in the BMS group (hazard ratio: 0.76; 95% confidence interval: 0.61 to 0.95; p = 0.011) as a result of lower MI (2.9% vs. 8.1%; p < 0.001) and TVR rates (5.9% vs.10.7%; p = 0.001) in the ZES group. Definite or probable stent thrombosis was also significantly reduced in ZES recipients (2.0% vs. 4.1%; p = 0.019).. Compared with BMS, DES implantation using a stent with a biocompatible polymer and fast drug-eluting characteristics, combined with an abbreviated, tailored DAPT regimen, resulted in a lower risk of 1-year MACE in uncertain candidates for DES implantation. (Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS] Study; NCT01385319).

Topics: Aged; Aged, 80 and over; Aspirin; Biocompatible Materials; Clopidogrel; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Hemorrhage; Humans; Immunosuppressive Agents; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Assessment; Risk Factors; Sirolimus; Ticlopidine; Treatment Outcome

Incomplete struts coverage is a predictor of late stent thrombosis after implantation of the drug-eluting stents (DES) in atherosclerotic lesions. The process of struts coverage in DES implanted for bare-metal stent (BMS) restenosis has never been described. Thirty-two patients with stable coronary artery disease were consecutively selected, 11 with BMS restenosis (group A) and 21 with de novo atherosclerotic lesions (group B). All patients underwent everolimus-eluting stent implantation; coronary angiography and optical coherence tomography were performed at 6 months follow-up. Percentage difference in struts coverage between the 2 groups was the primary end point. A total of 85,773 struts (17,891 in group A and 67,882 in group B) were analyzed: compared with group B, the percentage of uncovered stent struts was significantly lower in group A (2.6% vs 4.8%; p <0.0001). In group A, DES struts protruding out of BMS were more uncovered (5.0% vs 1.9%; p <0.0001) and malapposed (4.1% vs 2.1%; p <0.0001) compared with overlapping struts. In conclusion, when DES are implanted to treat BMS restenosis, struts coverage at 6 months follow-up is more complete compared with DES implanted in atherosclerotic lesions.

Topics: Antineoplastic Agents; Atherosclerosis; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Electrocardiography; Everolimus; Follow-Up Studies; Immunosuppressive Agents; Prosthesis Design; Reproducibility of Results; Retrospective Studies; Single-Blind Method; Sirolimus; Time Factors; Tomography, Optical Coherence

Most trials comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG) have not made use of second-generation drug-eluting stents.. We conducted a randomized noninferiority trial at 27 centers in East Asia. We planned to randomly assign 1776 patients with multivessel coronary artery disease to PCI with everolimus-eluting stents or to CABG. The primary end point was a composite of death, myocardial infarction, or target-vessel revascularization at 2 years after randomization. Event rates during longer-term follow-up were also compared between groups.. After the enrollment of 880 patients (438 patients randomly assigned to the PCI group and 442 randomly assigned to the CABG group), the study was terminated early owing to slow enrollment. At 2 years, the primary end point had occurred in 11.0% of the patients in the PCI group and in 7.9% of those in the CABG group (absolute risk difference, 3.1 percentage points; 95% confidence interval [CI], -0.8 to 6.9; P=0.32 for noninferiority). At longer-term follow-up (median, 4.6 years), the primary end point had occurred in 15.3% of the patients in the PCI group and in 10.6% of those in the CABG group (hazard ratio, 1.47; 95% CI, 1.01 to 2.13; P=0.04). No significant differences were seen between the two groups in the occurrence of a composite safety end point of death, myocardial infarction, or stroke. However, the rates of any repeat revascularization and spontaneous myocardial infarction were significantly higher after PCI than after CABG.. Among patients with multivessel coronary artery disease, the rate of major adverse cardiovascular events was higher among those who had undergone PCI with the use of everolimus-eluting stents than among those who had undergone CABG. (Funded by CardioVascular Research Foundation and others; BEST ClinicalTrials.gov number, NCT00997828.).

Topics: Aged; Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Complications; Prospective Studies; Sirolimus; Stroke

Studies have indicated varying mortality risks with timing of stent thrombosis (ST), but few have been adequately powered with prospective late follow-up. PROTECT randomized 8,709 subjects to either Endeavor zotarolimus-eluting or Cypher sirolimus-eluting stents. PROTECT Continued Access enrolled 1,018 patients treated with Endeavor zotarolimus-eluting stents. Subjects completed at least 4 and 3 years of follow-up, respectively. ARC-defined definite and probable ST events were stratified by time from index procedure: early (≤30 days), late (>30 and ≤360 days), and very late (>360 days). Rates of death and myocardial infarction were analyzed by ST timing. Median follow-up was 4.1 years. There were 184 ST events (1.9%): 61 early, 27 late, and 96 very late. Patient and procedural characteristics were similar between timing groups. There was no difference in dual-antiplatelet therapy use at discharge (97%) or 1 year (84%). Cardiac death in patients with ST at 4 years occurred in 32.1% compared with 2.5% in patients without ST (p <0.001). Combined rates of cardiac death and myocardial infarction did not differ according to ST timing, yet early ST was more commonly associated with cardiac death at 4 years than later ST (50.8% for early vs 18.5% for late vs 24.0% for very late; p <0.001). The relation between ST timing and outcomes did not differ between stent types. In conclusion, in prospective data, cardiac death was more common after early ST than later ST. Although ST remains infrequent, continued efforts to determine how to reduce ST, particularly within the first 30 days, are warranted. (The PROTECT trial is registered with ClinicalTrials.gov, number NCT00476957.).

Topics: Aged; Cause of Death; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Sirolimus

The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments.. In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (-0.25 mm, 95% CI -0.36 to -0.17 mm) when compared with patients without NA (-0.13 mm, 95% CI -0.17 to -0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years.. In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms.SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT00617084.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Disease Progression; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Neointima; Paclitaxel; Prosthesis Failure; Sirolimus; Tomography, Optical Coherence; Tubulin Modulators

Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) remains a major challenge.. This study evaluated the comparative efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients presenting with DES-ISR.. The study design of this multicenter randomized clinical trial assumed superiority of EES for the primary endpoint, in-segment minimal lumen diameter at the 6- to 9-month angiographic follow-up.. A total of 309 patients with DES-ISR from 23 Spanish university hospitals were randomly allocated to DEB (n = 154) or EES (n = 155). At late angiography (median 247 days; 90% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p < 0.01) (absolute mean difference: 0.23 mm; 95% CI: 0.07 to 0.38) [corrected], net lumen gain (1.28 ± 0.7 mm vs. 1.01 ± 0.7 mm; p < 0.01), and lower percent diameter stenosis (23 ± 22% vs. 30 ± 22%; p < 0.01) and binary restenosis rate (11% vs. 19%; p = 0.06), compared with patients in the DEB arm. Consistent results were observed in the in-lesion analysis. At the 1-year clinical follow-up (100% of patients), the main clinical outcome measure (composite of cardiac death, myocardial infarction, and target vessel revascularization) was significantly reduced in the EES arm (10% vs. 18%; p = 0.04; hazard ratio: 0.58; 95% CI: 0.35 to 0.98), mainly driven by a lower need for target vessel revascularization (8% vs. 16%; p = 0.035).. In patients with DES-ISR, EES provided superior long-term clinical and angiographic results compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent [RIBS IV]; NCT01239940).

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Sirolimus

To evaluate the outcomes of patients treated with a new drug-eluting stent formulation with low doses of sirolimus, built in an ultra-thin-strut platform coated with biodegradable abluminal coating.. This study is a randomized trial that tested the main hypothesis that the angiographic late lumen loss of the novel sirolimus-eluting stent is noninferior compared with commercially available biolimus-eluting stent. A final study population comprising 170 patients with one or two de novo lesions was randomized in the ratio 2:1 for sirolimus-eluting stent or biolimus-eluting stent, respectively. The primary endpoint was 9-month angiographic in-stent late lumen loss. Adverse clinical events were prospectively collected for 1 year.. After 9 months, the novel sirolimus-eluting stent was shown noninferior compared with the biolimus stent for the primary endpoint (angiographic in-stent late lumen loss: 0.20 ± 0.29 mm vs. 0.15 ± 0.20 mm, respectively; P value for noninferiority <0.001). The 1-year incidence of death, myocardial infarction, repeat revascularization, and stent thrombosis remained low and not significantly different between the groups.. The present randomized trial demonstrates that the tested novel sirolimus-eluting stent was angiographically noninferior in comparison with a last-generation biolimus-eluting stent.

Topics: Absorbable Implants; Aged; Brazil; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

Previously, we reported that the nine-month angiographic result after treatment of coronary bifurcation lesions with provisional T-stenting was not significantly different from that with routine T-stenting. To compare long-term clinical outcomes of the two stenting strategies, we extended the follow-up of our study on bifurcation stenting.. One hundred and one patients with coronary bifurcation lesions had been randomly assigned to provisional T-stenting and 101 to routine T-stenting, using sirolimus-eluting stents. We performed complete five-year follow-up. The primary efficacy endpoint was the incidence of target lesion revascularisation (TLR), and the primary safety endpoint was the incidence of definite/probable stent thrombosis (ST). We also monitored death, myocardial infarction (MI) and MACE (composite of death, MI and TLR). The cumulative five-year incidence of TLR in the provisional T-stenting arm was not significantly different from that in the routine T-stenting arm (16.2% vs. 16.3%, p=0.97). The same was true for MACE (22.8% vs. 22.9%, p=0.91), the composite of death and MI (9.9% vs. 13.9%, p=0.40), and ST (2.0% vs. 5.1%; p=0.25).. During five-year follow-up, routine T-stenting offered no advantage over provisional T-stenting with respect to TLR or MACE. ClinicalTrials.gov Identifier: NCT00288535

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The aim of this study was to evaluate the Sparrow sirolimus-eluting stent (Sparrow-SES) against the Sparrow bare-metal stent (Sparrow-BMS) and conventional balloon-expandable bare-metal stent (BMS: Driver/Micro-Driver stent, Medtronic Vascular, Santa Rosa, CA).. The Sparrow stent (Biosensors International, Singapore) consists of a guide wire-based, self-expandable, ultra-thin nitinol stent. The performance of this device with sirolimus in a fully biodegradable polymer has not been determined.. A total of 74 patients were included in this intravascular ultrasound (IVUS) sub-study of the CARE II trial, which was a prospective, randomized, multicenter trial in the treatment of single de novo native coronary artery lesions in vessels ranging from 2.0 mm to 2.75 mm in diameter (Sparrow-SES: n = 31, Sparrow-BMS: n = 22, BMS: n = 21).. Stent volume index (VI) was significantly increased 8-month later in Sparrow-SES and Sparrow-BMS, but not in BMS (4.0 ± 1.0 to 4.6 ± 1.0 mm(3) /mm, p<0.0001, 4.0 ± 0.6 to 4.4 ± 0.8 mm(3) /mm, p<0.05, and 5.2 ± 1.0 to 5.1 ± 0.9 mm(3) /mm, p=0.421, respectively). % neointimal obstruction in Sparrow-SES was significantly smaller than those in Sparrow-BMS and BMS at follow-up (17.6 ± 9.4 vs. 36.2 ± 13.8 and 39.9 ± 11.1%, p<0.001). Sparrow-SES showed a mean 15% stent expansion and good suppression of neointimal proliferation, resulting in a significantly lower percentage of change in lumen VI during follow-up period (Sparrow-SES: -6.2 ± 16.2%, Sparrow-BMS: -30.4 ± 11.6%, BMS: -40.4 ± 10.0%, p<0.001).. The self-expanding Sparrow-SES demonstrated chronic stent expansion, good suppression of neointimal proliferation and resulted in a more preserved lumen in stented small vessels compared with the Sparrow-BMS and conventional balloon expandable BMS.

Topics: Aged; Alloys; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Persistence of stent polymer coating has been associated with incomplete endothelialization, expansive vessel remodeling, neoatherosclerosis, and delayed healing associated with inflammation that may contribute to late adverse events.. The BICARE (Lepu Medical, Beijing, China) stent is a novel polymer-free, nanotechnology-based stent eluting sirolimus and probucol. As a first in human feasibility study, patients with a single de novo native coronary stenosis <30 mm in length and with reference vessel diameter from 2.5 to 4.0 mm underwent revascularization with the BICARE stent. The primary endpoint of target lesion failure (TLF) was assessed at 30 days. Secondary endpoints included in-stent late lumen loss and proportion of uncovered or malapposed stent struts by optical coherence tomography at 4-month angiographic surveillance.. Among 32 consecutive patients (age, 55.7 ± 8.7 years; men, 62.5%; diabetes, 18.8%), the average baseline reference vessel diameter and lesion length were 2.85 ± 0.48 mm and 15.0 ± 5.6 mm, respectively. At 30 days there was no occurrence of TLF. At 4 months (angiographic follow-up, N=32), angiographic in-stent late loss was 0.14 ± 0.19 mm, and the in-stent binary restenosis rate was 3.1%. Complete strut coverage was 98.2% with 0.2% malapposition among 16,751 analyzed struts. At 18 months, TLF occurred in 3 (9.4%) patients related to repeat revascularization with no adverse safety events identified.. The preliminary feasibility and safety of a polymer-free, dual-drug eluting stent are demonstrated by absence of early adverse safety events and favorable angiographic suppression of neointimal hyperplasia. Stent imaging suggests favorable healing with extensive stent strut coverage and very low malapposition. These findings further inform comparison with biopermanent polymer DES.

Topics: Cardiovascular Agents; China; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug Combinations; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Probucol; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate the effects of the everolimus-eluting Xience™/Promus™ stent (EES) and the sirolimus-eluting Cypher™ stent (SES) on intimal hyperplasia (IH) in diabetic patients.. Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to intimal hyperplasia (IH).. In a sub study of the Randomized Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents in Patients Treated with Percutaneous Coronary Intervention (SORT OUT IV trial), serial intravascular ultrasound (IVUS) 10-month follow-up data were available in 88 patients, including 48 EES and 40 SES treated patients. IVUS endpoints included IH volume, in-stent % volume obstruction and changes in external elastic membrane (EEM) volume.. Compared with the SES group, IH volume was increased in the EES group [median (interquartile range): 2.8 mm(3) (0.0-12.6) vs. 0.0 mm(3) (0.0-1.1), P = 0.001]. In-stent % volume obstruction was increased in EES compared to SES [median (interquartile range): 1.6% (0.0-8.2) vs. 0.0% (0.0-1.0), P = 0.001]. Peri-stent external elastic membrane (EEM) volume: (post procedure vs. follow-up EES [300 mm(3) (219-491) vs. 307 mm(3) (223-482), P = 0.73] and SES [316 mm(3) (235-399) vs. 323 mm(3) (246-404), P = 0.05]) and peri-stent plaque volume: EES [163 mm(3) (103-273) vs. 184 mm(3) (115-291), P = 0.18] and SES [186 mm(3) (139-248) vs. 175 mm(3) (153-243), P = 0.26]) were unchanged in both groups. In the proximal reference segment a significant increase in plaque area was seen in the EES group only, without vascular remodeling.. In diabetic patients, EES stent implantation was associated with increased IH volume obstruction without involvement of vascular remodeling.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Remodeling

Different approaches of local intravascular drug delivery may influence endothelial and microvascular function. The aim of this trial was to study the influence of a paclitaxel coated balloon in combination with a bare metal stent (DCB + BMS) versus a bare metal stent (BMS) or a sirolimus-eluting stent (DES) on coronary restenosis and endothelial function.. This prospective trial included 77 patients with coronary de novo lesions. The patients were assigned to either one of the treatment groups. After 9 months, patients underwent angiographic follow-up including invasive measurement of coronary endothelial function. After 9 months, late lumen loss in-stent was highest in the BMS group (0.85 ± 0.73 mm), lower in DCB + BMS (0.36 ± 0.46 mm); and lowest in the DES group (0.25 ± 0.34 mm; P = 0.001 [ANOVA]). When compared to the BMS group, in-segment late lumen loss was significantly reduced in the DCB + BMS group (0.27 ± 0.43 mm vs. 0.60 ± 0.55 mm, P = 0.029) and the DES group (0.28 ± 0.40 mm, P = 0.045). Coronary flow reserve was significantly higher with the DCB + BMS treatment (3.16 ± 0.97 vs. 2.42 ± 0.99 [BMS], P = 0.036) whereas the increase in the DES group did not reach the significance level (3.06 ± 1.39, P = 0.144 vs. BMS). Parameters of endothelial function like intracoronary flow velocity and vessel diameter distal to the stented area showed similar patterns of response to adenosine, acetylcholine, and nitro in all groups.. DES and the combination of DCB + BMS showed a significant reduction of late lumen loss as compared to a BMS alone. Furthermore, both types of local drug delivery were not associated with a deterioration of microvascular function at 9 months [ClinicalTrials.gov Identifier: NCT00473499].

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Circulation; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Endothelium, Vascular; Female; Hemodynamics; Humans; Male; Metals; Microcirculation; Middle Aged; Paclitaxel; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Time Factors; Vasodilator Agents

Early-generation drug-eluting stent (DES) overlap (OL) is associated with impaired long-term clinical outcomes whereas the impact of OL with newer-generation DES is unknown. Our aim was to assess the impact of OL on long-term clinical outcomes among patients treated with newer-generation DES.. We analysed the three-year clinical outcomes of 3,133 patients included in a prospective DES registry according to stent type (sirolimus-eluting stents [SES; N=1,532] versus everolimus-eluting stents [EES; N=1,601]), and the presence or absence of OL. The primary outcome was a composite of death, myocardial infarction (MI), and target vessel revascularisation (TVR). The primary endpoint was more common in patients with OL (25.1%) than in those with multiple DES without OL (20.8%, adj HR=1.46, 95% CI: 1.03-2.09) and patients with a single DES (18.8%, adj HR=1.74, 95% CI: 1.34-2.25, p<0.001) at three years. A stratified analysis by stent type showed a higher risk of the primary outcome in SES with OL (28.7%) compared to other SES groups (without OL: 22.6%, p=0.04; single DES: 17.6%, p<0.001), but not between EES with OL (22.3%) and other EES groups (without OL: 18.5%, p=0.30; single DES: 20.4%, p=0.20).. DES overlap is associated with impaired clinical outcomes during long-term follow-up. Compared with SES, EES provide similar clinical outcomes irrespective of DES overlap status.

Topics: Adult; Aged; Aged, 80 and over; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Sirolimus; Time; Treatment Outcome

Drug-eluting stents (DES) constitute a major achievement in preventing re-stenosis, concerns remain regarding the increased inflammatory responses associated with the polymers used. This analysis focuses on outcomes in patients receiving the polymer-free sirolimus-eluting stent system YUKON-Choice (Yukon-DES, Translumina, Germany).. From 01/2006-09/2008 all patients receiving Yukon-DES (≥2.5 mm diameter) were prospectively enrolled in our registry. The primary endpoint was long-term major adverse cardiac events (MACE).. 701 patients were included in our registry. Mean age was 65.7 ± 10 years (73% male gender, 35.5% diabetes, and 32.2% acute coronary syndrome). 76% of the lesions were of Type B2/C. Lesion length was 24.6 ± 5.2 mm and mean stent diameter was 2.8 ± 0.4 mm. A total of 511 pts (72%) underwent 6-months angiographic follow-up, target vessel revascularization was noted in 23.5%. At 5 years clinical outcomes were: cardiac death 5.8%; myocardial infarction 3.4%; and TVR 24.6%. The incidence of MACE differed significantly between "on-label" and "off-label" indications (14.8% vs. 40.8% MACE; P < 0.001). Incidence of definitive/probable stent thrombosis (ST) was 1.14% (8/701); very late (>1 year) ST occurred in 0.29%.. Our data suggests that the implantation of the sirolimus-coated polymer-free YUKON-DES is safe and feasible with a very low incidence of ST in this real world patient cohort with high percentage of diabetes and small vessels.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Germany; Humans; Incidence; Male; Polymers; Prospective Studies; Registries; Sirolimus; Survival Rate; Time Factors

This study sought to evaluate the impact of anatomic and procedural variables on the outcome of the unprotected left main coronary artery (uLMCA) itself after drug-eluting stent (DES) implantation.. There is a controversial debate regarding when and how to perform percutaneous coronary intervention (PCI) for an uLMCA stenosis.. This analysis is based on a randomized study of 607 patients undergoing PCI for uLMCA, randomized 1:1 to receive paclitaxel- or sirolimus-eluting stents. We evaluated the impact of the SYNTAX score, uLMCA anatomy, and stenting technique on in-stent restenosis (ISR), target lesion revascularization (TLR), and the 3-year outcomes.. The 3-year cardiac mortality rate was 5.8%; 235 (39%) patients had a true bifurcation lesion (TBL), and the median SYNTAX score was 27. TBL was associated with a higher need for multiple stents (72% vs. 37%, p < 0.001). TBL was a significant predictor of ISR (23% vs. 14%, p = 0.008) and for TLR (18% vs. 9%, p < 0.001). The need for multiple stents was a predictor of ISR (22% vs. 13%, p = 0.005) and for TLR (16% vs. 9%, p = 0.005). Culotte stenting showed better results compared with T-stenting for ISR (21% vs. 56%, p = 0.02) and for TLR (15% vs. 56%, p < 0.001). We observed a significant association between uLMCA-TLR and SYNTAX scores (9.2% for scores ≤ 22, 14.9% for scores 23 to 32, and 13.0% for scores ≥ 33, p = 0.008).. PCI of uLMCA lesions with DES is safe and effective out to 3 years. TBL and multiple stents were independent predictors for ISR. In the multivariate analysis, independent predictors for TLR were TBL, age, and EuroSCORE (European System for Cardiac Operative Risk Evaluation). (Drug-Eluting-Stents for Unprotected Left Main Stem Disease [ISAR-LEFT-MAIN]; NCT00133237).

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Proportional Hazards Models; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

This study sought to assess device-specific outcomes after implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients undergoing percutaneous coronary intervention.. Few studies have directly compared second-generation drug-eluting stents with each other or with BMS.. We randomized 2,013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group received up to 6 or 24 months of clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse cardiac event (MACE) including any death, myocardial infarction, or target vessel revascularization, whereas the cumulative rate of definite or probable stent thrombosis (ST) was the key safety endpoint.. Clinical follow-up at 2 years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%; 95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1 to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%; 95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi-square = 16.9; p = 0.0001).. Our study shows that cumulative MACE rate, encompassing both safety and efficacy endpoints, was lowest for EES, highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS also with respect to the safety endpoints with regard to definite or probable and definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

Topics: Aged, 80 and over; Chi-Square Distribution; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Italy; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prosthesis Design; Risk Factors; Sirolimus; Stents; Ticlopidine; Time Factors; Treatment Outcome

Restenosis is a frequent complication of coronary stent implantation, especially bare metal stent (BMS) implantation. The everolimus-eluting stent (EES) has previously been shown to be efficacious in the treatment of de novo lesions. We performed this study to evaluate clinical, angiographic and IVUS results after EES implantation for the treatment of BMS ISR. XERES was a prospective, multicentre, nationwide study, enrolling 97 consecutive patients with in-stent restenosis (ISR) after BMS implantation across 20 centres in France. Suitable lesions had a reference vessel diameter between 2.5 mm and 4 mm, a length ≤22 mm and a diameter stenosis between 50 and 100%. The primary endpoint was angiographic in-stent late loss (LL) as determined by quantitative coronary angiography (QCA) at nine-month follow-up. QCA was required to be performed in each included patient and IVUS was performed in a subgroup of 27 patients. At nine-month follow-up, the in-stent late loss was 0.35±0.63 mm. The rate of in-stent binary restenosis was 12.22%, including two complete occlusions. The average volume of neointimal hyperplasia was 15.6±9.9 mm3. The in-stent percent volume obstruction was 8.5±5.2%. The in-segment percent area and diameter obstruction were 32±17% and 27±11%, respectively. Two initial malappositions were persistent and two other patients had late acquired stent malapposition. The cumulative incidence of major adverse cardiac events (MACE) was 10.1%. EES for the treatment of bare metal in-stent restenosis seemed safe and efficacious.

Topics: Adult; Aged; Aged, 80 and over; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; France; Humans; Hyperplasia; Male; Middle Aged; Myocardial Infarction; Neointima; Prospective Studies; Sirolimus; Stents; Thrombosis; Ultrasonography, Interventional

Patients with diabetes mellitus have a higher risk of adverse events after percutaneous coronary intervention (PCI). This study aimed to elucidate the relative efficacy of everolimus-eluting stents (EES) versus sirolimus-eluting stents (SES) according to diabetic status.. Data from the EXCELLENT randomised trial and registry were pooled in a per protocol analysis manner. The primary endpoint was target lesion failure (TLF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularisation. Among a total of 6,524 patients, 2,404 (36.8%) had diabetes mellitus. Patients with diabetes were shown to have a higher rate of TLF after PCI, which was mainly driven by differences in cardiac death and myocardial infarction, while the rate of repeat revascularisation and stent thrombosis did not differ significantly. TLF occurred at a similar rate between patients treated with EES versus SES in each subgroup stratified by diabetic status (interaction p=0.384). In addition, no significant interactions were present with regard to any pre-specified clinical endpoints. The results were corroborated by analysis with inverse probability of treatment weighting (interaction p=0.329). We also found that insulin-dependent diabetes imposed an even greater risk of TLF on patients treated with PCI.. Despite the recent advances in drug-eluting stent technology, diabetic patients are still at higher risk of adverse clinical events after PCI than those without diabetes mellitus. Whether a patient was treated with EES or SES had no significant interaction with diabetic status in terms of clinical outcome after PCI.

Topics: Aged; Case-Control Studies; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome

Second-generation everolimus-eluting stents (EES) and third generation biolimus-eluting stents (BES) have been shown to be superior to first-generation paclitaxel-eluting stents (PES) and second-generation sirolimus-eluting stents (SES). However, neointimal proliferation and very late stent thrombosis is still an unresolved issue of drug-eluting stent (DES) implantation overall. The Absorb™ (Abbott Vascular, Abbott Park, IL, USA) is the first CE approved DES with a bioresorbable vascular scaffold (BVS) thought to reduce long-term complication rates. The EVERBIO II trial was set up to compare the BVS safety and efficacy with both EES and BES in all patients viable for inclusion.. The EVERBIO II trial is a single-center, assessor-blinded, randomized trial. The study population consists of all patients aged≥18 years old undergoing percutaneous coronary intervention. Exclusion criterion is where the lesion cannot be treated with BVS (reference vessel diameter>4.0 mm). A total of 240 patients will be enrolled and randomly assigned into 3 groups of 80 with either BVS, EES or BES implantation. All patients will undergo a follow-up angiography study at 9 months. Clinical follow-up for up to 5 years will be conducted by telephone. The primary endpoint is in-segment late lumen loss at 9 months measured by quantitative coronary angiography. Secondary endpoints are patient-oriented major adverse cardiac event (MACE) (death, myocardial infarction and target-vessel revascularization), device-oriented MACE (cardiac death, myocardial infarction and target-lesion revascularization), stent thrombosis according to ARC and binary restenosis at follow-up 12 months angiography.. EVERBIO II is an independent, randomized study, aiming to compare the clinical efficacy, angiographic outcomes and safety of BVS, EES and BES in all comer patients.. The trial listed in clinicaltrials.gov as NCT01711931.

Topics: Absorbable Implants; Cardiovascular Agents; Clinical Protocols; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Prosthesis Design; Research Design; Sirolimus; Switzerland; Time Factors; Tissue Scaffolds; Treatment Outcome

This study sought to compare the efficacy of drug-eluting balloons (DEB) with that of everolimus-eluting stents (EES) in patients with bare-metal stents (BMS) in-stent restenosis (ISR).. Treatment of patients with ISR remains a challenge.. This was a prospective, multicenter, randomized trial comparing DEB with EES in patients with bare-metal stents (BMS) in-stent restenosis (ISR). The primary endpoint was the minimal lumen diameter at 9 months' follow-up.. A total of 189 patients with BMS-ISR from 25 Spanish sites were included (95 were allocated to DEB and 94 to EES). Procedural success was achieved in all patients. At late angiography (median 249 days; 92% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm, p < 0.001; absolute mean difference: 0.35 mm; 95% confidence interval [CI]: 0.16 to 0.53) and a lower percent of diameter stenosis (13 ± 17% vs. 25 ± 20%, p < 0.001). However, late loss (0.04 ± 0.5 mm vs. 0.14 ± 0.5 mm, p = 0.14) and binary restenosis rate (4.7% vs. 9.5%, p = 0.22) were very low and similar in both groups. Clinical follow-up (median 365 days) was obtained in all (100%) patients. Occurrences of the combined clinical outcome measure (cardiac death, myocardial infarction, and target vessel revascularization; 6% vs. 8%; hazard ratio [HR]: 0.76; 95% CI: 0.26 to 2.18, p = 0.6) and the need for target vessel revascularization (2% vs. 6%; HR: 0.32: 95% CI: 0.07 to 1.59, p = 0.17) were similar in the 2 groups.. In patients with BMS-ISR, both DEB and EES provided excellent clinical results with a very low rate of clinical and angiographic recurrences. However, compared with DEB, EES provide superior late angiographic findings. (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-eluting Balloon vs. Everolimus-eluting Stent [RIBS V]; NCT01239953).

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Metals; Middle Aged; Paclitaxel; Prospective Studies; Prosthesis Design; Prosthesis Failure; Risk Assessment; Severity of Illness Index; Sirolimus; Spain; Survival Rate; Treatment Outcome

The Absorb everolimus-eluting bioresorbable vascular scaffold (AbsorbBVS) is a completely resorbable device engineered to overcome the limitations of permanent metallic stents, providing temporary scaffolding and antiproliferative drug delivery for the treatment of obstructive coronary artery disease.. The objective of the AIDA trial is to evaluate the efficacy and performance in an contemporary all-comer population of the AbsorbBVS strategy vs the XIENCE family everolimus-eluting metallic coronary stent system in the treatment of coronary lesions. The AIDA trial is a prospective, randomized (1:1), active-control, single-blinded, all-comer, noninferiority trial. A total of 2,690 subjects will be enrolled with broad inclusion and limited exclusion criteria according to the "Instructions for Use" of the AbsorbBVS strategy. The study population includes both simple and complex lesions, in patients with stable and acute coronary syndrome. The follow-up continues for 5years. The primary end point of the trial is target vessel failure, defined as the composite of cardiac death, myocardial infarction, and target vessel revascularization, at 2years. This study is registered on ClinicalTrials.gov with number NCT01858077.. The AIDA trial will provide the first randomized direct comparison between the everolimus-eluting bioresorbable vascular scaffold and the everolimus-eluting metallic stent in contemporary percutaneous coronary intervention practice.

Topics: Aged; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Single-Blind Method; Sirolimus; Treatment Outcome

There are conflicting data on the use of cilostazol as triple antiplatelet therapy (TAPT) for improving clinical outcomes after drug-eluting stent implantation. We aimed to evaluate whether 3-month use of cilostazol in addition to dual antiplatelet therapy (DAPT) improved clinical outcomes in patients with long or multivessel coronary artery disease (CAD) after biolimus-eluting stent (BES) implantation.. Patients (n = 630) who had been successfully treated with BES implantation for lesions with ≥28 mm in stent length or ≥2 stents for different coronary arteries were enrolled in this prospective randomized multicenter trial. All patients were randomly assigned to receive either DAPT (aspirin and clopidogrel for 12 months, n = 314) or TAPT (DAPT plus 3-month cilostazol use, n = 316). The primary end point was a device-oriented composite consisting of cardiac death, myocardial infarction (not clearly attributable to a nontarget vessel), and ischemia-driven target lesion revascularization at 1-year follow-up.. A total of 314 patients in DAPT and 308 patients in TAPT were analyzed. Multivessel CAD was present in 65.7% of patients. Stents ≥28 mm in length were implanted in 58.1% of lesions. There were no significant differences in baseline and angiographic characteristics between the 2 groups. The primary end point was similar between the 2 groups (2.3% in DAPT vs 1.9% in TAPT, log-rank P = .799).. In patients treated with BES implantation for long or multivessel CAD, 3 months of cilostazol use in addition to DAPT did not improve clinical outcome at 1-year follow-up.

Topics: Aged; Cilostazol; Clopidogrel; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Sirolimus; Tetrazoles; Ticlopidine; Time Factors; Treatment Outcome

We sought to compare the healing patterns of biolimus-eluting stents with biodegradable polymer (BP-BES, Nobori) versus everolimus-eluting stents with permanent polymer (PP-EES, Xience) using intravascular optical coherence tomography (OCT). A total of 34 patients undergoing treatment of de novo coronary lesions were randomly assigned to receive BP-BES (n = 15) or PP-EES (n = 19). Stent tissue coverage and apposition as well as the incidence of peri-strut low intensity area (PLIA) were assessed by OCT at 6-8 months. Generalized linear mixed models were used to account for clustered data. OCT imaging was available for 17 lesions with 2,805 struts in the BP-BES group and 22 lesions with 3,890 struts in the PP-EES group. BP-BES as compared to PP-EES showed similar rates of uncovered struts (479 vs. 588, odds ratio (OR) 1.54 (95 % CI 0.63-3.79), P = 0.34) and malapposed struts (46 vs. 32 struts, OR 1.64 [95 % CI 0.21-12.5], P = 0.64). Three lesions with BP-BES (17.6 %) versus 5 lesions with PP-EES (22.7 %) had >30 % uncovered struts (P = 0.78). The proportion of patients with PLIA was similar in both groups (BP-BES 41.2 % vs. PP-EES 36.4 %, OR 1.11 [95 % CI 0.43-2.87], P = 0.83). New generation BP-BES as compared to PP-EES showed similar stent coverage and apposition as assessed by OCT at 6-8 months. In addition, PLIA-possible markers of delayed arterial healing-were observed with similar frequency in both groups.

Topics: Aged; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Immunosuppressive Agents; Male; Materials Testing; Odds Ratio; Polymers; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES).. Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥ 3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43).. A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).

Topics: Aspirin; Blood Vessel Prosthesis; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Failure; Sirolimus; Ticlopidine; Treatment Outcome

In head-to-head comparisons of coronary drug-eluting stents, the primary endpoint is traditionally assessed after 9-12 months. However, the optimum timepoint for this assessment remains unclear. In this study, we assessed clinical outcomes at up to 5 years' follow-up in patients who received two different types of drug-eluting stents.. We undertook this multicentre, open-label, randomised superiority trial at five percutaneous coronary intervention centres in Denmark. We randomly allocated 2332 eligible adult patients (≥18 years of age) with an indication for drug-eluting stent implantation to the zotarolimus-eluting Endeavor Sprint stent (Medtronic, Santa Rosa, CA, USA) or the sirolimus-eluting Cypher Select Plus stent (Cordis, Johnson & Johnson, Warren, NJ, USA). Randomisation of participants was achieved by computer-generated block randomisation and a telephone allocation service. The primary endpoint of the SORT OUT III study was a composite of major adverse cardiac events-cardiac death, myocardial infarction, and target vessel revascularisation-at 9 months' follow-up. In this study, endpoints included the occurrence of major adverse cardiac events and definite stent thrombosis at follow-up times of up to 5 years. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00660478.. We randomly allocated 1162 patients to receive the zotarolimus-eluting stent and 1170 to the sirolimus-eluting stent. At 5-year follow-up, rates of major adverse cardiac events were similar in patients treated with both types of stents (zotarolimus-eluting stents 197/1162 [17.0%] vs sirolimus-eluting stents 182/1170 [15.6%]; odds ratio [OR] 1.10, 95% CI 0.88-1.37; p=0.40). This finding was indicative of the directly contrasting results for rates of major adverse cardiac events at 1-year follow up (zotarolimus 93/1162 [8.0%] vs sirolimus 46/1170 [3.9%]; OR 2.13, 95% CI 1.48-3.07; p<0.0001) compared with those at follow-up between 1 and 5 years (104 [9.0%] vs 136 [11.6%]; OR 0.78, 95% CI 0.59-1.02; p=0.071). At 1-year follow-up, definite stent thrombosis was more frequent after implantation of the zotarolimus-eluting stent (13/1162 [1.1%]) than the sirolimus-eluting stent (4/1170 [0.3%]; OR 3.34, 95% CI 1.08-10.3; p=0.036), whereas the opposite finding was recorded for between 1 and 5 years' follow-up (zotarolimus-eluting stent 1/1162 [0.1%] vs sirolimus-eluting stent 21/1170 [1.8%], OR 0.05, 95% CI 0.01-0.36; p=0.003). 26 of 88 (30%) target lesion revascularisations in the zotarolimus-eluting stent group occurred between 1 and 5 years' follow-up, whereas 54 of 70 (77%) of those in the sirolimus-eluting stent group occurred during this follow-up period.. The superiority of sirolimus-eluting stents compared with zotarolimus-eluting stents at 1-year follow-up was lost after 5 years. The traditional 1-year primary endpoint assessment therefore might be insufficient to predict 5-year clinical outcomes in patients treated with coronary drug-eluting stent implantation.. Cordis and Medtronic.

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Cytostatic Agents; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Research Design; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

Concern exists relating to potential attenuated efficacy of limus-eluting stents in patients with diabetes mellitus. In this respect diabetic patients with sirolimus-eluting stent (SES) failure requiring reintervention may be expected to derive particular benefit from a treatment-switch to paclitaxel-eluting stent (PES) implantation.. The aim of the current report was to investigate outcomes of patients with SES restenosis randomized to treatment with SES (same stent strategy) or PES (switch stent strategy) in the pre-specified subgroups of patients with and without diabetes mellitus.. In the setting of ISAR-DESIRE 2 trial, 450 patients with clinically significant SES restenosis were randomly assigned to receive either SES or PES. The primary end point was in-stent late loss at 6-8month follow-up angiography. Secondary endpoints were binary angiographic restenosis (diameter stenosis >50%) and target lesion revascularization (TLR), the composite of death or myocardial infarction (MI) and definite stent thrombosis at 12months.. Of 450 patients enrolled, 162 (36.0%) had a diagnosis of diabetes mellitus. In patients with diabetes 86 patients were randomly assigned to SES versus 76 to PES. In patients without diabetes 139 were assigned to SES versus 149 to PES. Late loss was comparable between SES and PES both in patients with diabetes (0.38±0.59mm vs. 0.37±0.59mm; p=0.97) and without (0.41±0.67mm vs. 0.38±0.6mm; p=0.98; pinteraction=0.89). Similarly binary restenosis was comparable between SES and PES in patients with diabetes (19.0% vs. 26.0%; p=0.32) or without (18.9% vs. 17.8%; p=0.98; pinteraction=0.36). TLR, death or MI and definite stent thrombosis were also similar in SES versus PES treatment groups regardless of diabetes status.. In cases of SES-restenosis, treatment with either repeat SES or switch to PES was associated with a comparable degree of efficacy, regardless of diabetic status.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Diabetes Complications; Drug-Eluting Stents; Female; Germany; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Patient Selection; Percutaneous Coronary Intervention; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The use of drug-eluting stents (DES) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is controversial and not yet endorsed in clinical guidelines.. This was an a priori planned post hoc analysis involving 754 NSTE-ACS patients from the randomised BASKET-PROVE trial (sirolimus-eluting stent vs. everolimus-eluting stent vs. bare metal stent in large-vessel stenting). The primary endpoint was the combined two-year rate of cardiovascular death or non-fatal myocardial infarction (MI). Secondary endpoints were each component of the primary endpoint, and clinically indicated target vessel revascularisation (TVR) and stent thrombosis. Compared to patients with BMS, those treated with SES and EES had a strong trend towards lower two-year rates of the primary endpoint (HR: 0.31 [CI: 0.11-0.90], p=0.03, and HR: 0.74 [CI: 0.44-1.24], p=0.25), and of TVR (HR: 0.58 [CI: 0.29-1.15], p=0.12) and (HR: 0.52 [CI: 0.34-0.78], p=0.002). When the SES and EES groups were combined and compared to BMS, significant reductions in both cardiovascular death/MI and TVR were found.. Compared with BMS, use of DES in NSTE-ACS patients undergoing stent implantation in large vessels was associated with a reduction in both TVR and the combined endpoint consisting of cardiovascular death/MI. Thus, DES use improves both efficacy and safety. These findings support the use of DES in NSTE-ACS patients.

Topics: Acute Coronary Syndrome; Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Proportional Hazards Models; Sirolimus; Stents; Thrombosis; Treatment Outcome

Long-term clinical outcomes of everolimus-eluting stent (EES) compared with sirolimus-eluting stent (SES) have not been evaluated fully yet, especially whether EES implantation could positively affect late adverse events reported after SES implantation occurring >1 year.. In this all-comer prospective multicenter randomized open-label trial, 3196 patients were assigned randomly to implant either EES (n=1596) or SES (n=1600). At 3 years, EES was noninferior to SES on the primary safety end point (all-cause death or myocardial infarction; 10.1% versus 11.5%; noninferiority P <0.001; and superiority P=0.19). Cumulative incidence of definite stent thrombosis was low and was not significantly different between the 2 groups (0.5% versus 0.6%; P=0.81). There was no significant difference in the efficacy end point of target-lesion revascularization between the EES and SES groups (6.6% versus 7.9%; P=0.16). However, the cumulative incidence of target-lesion failure (cardiac death/target-vessel myocardial infarction/ischemia-driven target-lesion revascularization) was significantly lower in the EES group than in the SES group (8.8% versus 11.4%; P=0.01). By a landmark analysis at 1 year, the cumulative incidence of very late stent thrombosis and late target-lesion revascularization was not significantly different between the 2 groups (0.2% versus 0.2%; P=0.99 and 2.2% versus 2.9%; P=0.21, respectively).. The efficacy and safety outcomes for this trial after EES implantation remained comparable with those after SES implantation through 3-year follow-up. However, improvement of clinical outcome after EES implantation compared with SES implantation was suggested by the significantly lower cumulative incidences of target-lesion failure, which has been the most widely used primary end point in the stent-versus-stent trials.. http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Topics: Aged; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Thrombosis; Treatment Outcome

Procedural and clinical outcomes still remain unfavorable for patients with long coronary lesions who undergo percutaneous coronary intervention. The current study, therefore, evaluated 2 innovative drug-eluting stents for the management of long-lesion coronary artery disease.. This randomized, multicenter, prospective trial, called the Long Drug-Eluting Stent (LONG-DES) V trial, compared the biodegradable polymer-based biolimus A9-eluting stent (BES) and the durable polymer-based platinum chromium everolimus-eluting stent (PtCr-EES) in 500 patients with long (≥ 25 mm) coronary lesions. The primary end point of the trial was in-segment late luminal loss at the 9-month angiographic follow-up. The BES and PtCr-EES groups had similar baseline characteristics, with a slightly shorter lesion length in the BES group versus the PtCr-EES group (29.24 ± 12.17 versus 32.27 ± 13.84 mm; P = 0.016). In-segment late luminal loss was comparable between the 2 groups at the 9-month angiographic follow-up (BES, 0.14 ± 0.38 versus PtCr-EES, 0.11 ± 0.37 mm; difference, 0.031; 95% confidence interval, -0.053 to 0.091; P = 0.03 for a noninferiority margin of 0.11, P = 0.45 for superiority), as was in-stent late luminal loss (0.20 ± 0.41 versus 0.24 ± 0.38 mm; P = 0.29). The incidence of in-segment (6.1% versus 4.9%; P = 0.63) and in-stent (3.7% versus 4.9%; P = 0.59) binary restenosis was also similar between the groups. There was no significant between-group difference in the rate of composite outcome of death, myocardial infarction, and target vessel revascularization (41, 16.7% in BES versus 42, 16.5% in PtCr-EES; P=0.94).. BES and PtCr-EES implantation showed analogous angiographic and clinical outcomes for patients with de novo long coronary lesions.. http://www.clinicaltrials.gov. Unique identifier: NCT01186120.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Single-Blind Method; Sirolimus; Survival Rate; Thrombosis; Treatment Outcome

Paclitaxel drug-eluting balloons (pDEB) could be an attractive option to minimise side branch (SB) restenosis in bifurcated coronary lesions. We compared angiographic and clinical outcomes with pDEB plus bare metal stent (BMS) versus drug-eluting stents (DES) in de novo bifurcated lesions.. This multicentre randomised trial included 108 patients. Sequential main branch (MB)/SB dilatation with pDEB, with provisional T-stenting with BMS in the MB was performed in the pDEB group, and with everolimus DES in the DES group. The primary endpoint was late lumen loss (LLL) at nine months. The secondary endpoint was the incidence of major adverse cardiac events (MACE: death, myocardial infarction, or target lesion revascularisation). In-segment MB LLL was 0.31±0.48 mm in the pDEB group, and 0.16±0.38 mm in the DES group (p=0.15); mean difference was 0.15 mm (upper limit one-sided 95% CI: 0.27 mm; p=0.001; non-inferiority test). LLL in SB was -0.04±0.76 mm in the pDEB group and -0.03±0.51 mm in the DES group (p=0.983). MACE and TLR were higher in the pDEB group (17.3% vs. 7.1%; p=0.105, and 15.4% vs. 3.6%; p=0.045), due to higher MB restenosis (13.5% vs. 1.8%; p=0.027).. pDEB bifurcation pretreatment with BMS implantation in MB showed greater LLL (ns) and increased incidence of MACE compared to everolimus DES. Both strategies showed similar results in the SB.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Platelet Aggregation Inhibitors; Sirolimus; Stents; Ticlopidine; Treatment Outcome; Tubulin Modulators

Up to 25% of patients who undergo a percutaneous coronary intervention show some limitation in the use of drug-eluting stents. The aim of this study was to evaluate if titanium-nitride-oxide-coated stents could be a good alternative to everolimus-eluting stents in diabetic patients.. A total of 173 diabetic patients with lesions at moderate risk of restenosis (exclusion criteria: diameter < 2.5 mm or length > 28 mm in vessels < 3mm, chronic occlusion) were randomized to a titanium group (83 patients) or an everolimus group (90 patients).. Baseline characteristics were well balanced; 28.3% of patients were insulin dependent. At 1 year, the incidence of major adverse cardiac events (death, nonfatal myocardial infarction, stroke, or repeat target vessel revascularization) was significantly higher in the titanium group than in the everolimus group (total, 14.5% vs 4.4%; P = .02; noninsulin-dependent subgroup, 9.7% vs 3.2%; P = .14; insulin-dependent subgroup, 28.6% vs 7.1%; P = .04). The incidence of death, nonfatal myocardial infarction, stroke, or any revascularization was 16.9% in the titanium group and 7.8% in the everolimus group (P = .06). Target lesion and vessel revascularizations occurred in 8.4% compared with 3.3% (P = .15) and in 13.3% compared with 3.3% (P = .01) in the titanium and everolimus groups, respectively. Angiographic follow-up at 9 months showed significantly less late lumen loss in the everolimus group (in-segment, 0.52 [standard deviation, 0.58) mm vs -0.05 [0.32] mm; in-stent, 0.76 [0.54] mm vs 0.13 [0.31] mm; P < .0001).. The everolimus-eluting stent is superior to the titanium stent for clinical and angiographic end points in diabetic patients with lesions at moderate risk of restenosis.

Topics: Aged; Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Stents; Titanium

To our knowledge, no randomised study has compared rates of uncovered stent struts in everolimus (EES) vs. new-generation zotarolimus-eluting (ZES-R) stents in acute coronary syndrome (ACS). The aim of our study was to evaluate the completeness of neointimal coverage with optical coherence tomography (OCT) in ACS patients treated with drug-eluting stents (DES) comparing EES versus new-generation ZES-R.. All eligible ACS patients admitted to four Italian centres with a clinical indication for culprit lesion intervention were randomised 1:1 to EES or ZES-R. The primary study endpoint was the percentage of uncovered stent struts evaluated by optical coherence tomography (OCT) at six months. Secondary endpoints were the percentage of malapposed stent struts, percent neointimal hyperplasia cross-sectional area (CSA) and major adverse cardiac events (MACE) at six months. A total of 60 patients were randomised to EES (n=29) or ZES-R (n=31). No differences were observed in baseline characteristics between the two groups. Overall, 31.7% presented with STEMI, of which 68.4% were anterior. The other patients comprised 41.7% NSTEMI and 26.7% troponin-negative ACS. A mean of 1.3±0.6 lesions were treated per patient, with a mean of 1.3±0.5 stents per lesion. At 30 days there was one sudden death. Six-month OCT analysis was performed in 25 lesions in the EES group and in 24 lesions in the ZES-R group. There was no difference in the primary endpoint of uncovered stent struts between groups (EES 6.42% [3.27, 9.57] vs. ZES-R 7.07% [3.22, 10.92]; p=0.80). Furthermore, there were no differences between groups in the percentage of malapposed stent struts, either with (EES 1.19% [0.34, 2.04] vs. ZES-R 0.85% [0.40, 1.30]; p=0.49) or without coverage (EES 1.06% [0.12, 2.01] vs. ZES-R 0.24% [0.05, 0.44]; p=0.09). Percent neointima CSA was similar in both groups (EES 37.0% [18.6, 55.3] vs. ZES-R 26.6% [18.4, 34.8]; p=0.31). At six-month clinical follow-up, no additional patients died or suffered MI. There were four MACE in the EES group and one in the ZES-R group.. In our study, in patients presenting with ACS, both EES and ZES-R had low percentages of malapposed and uncovered stent struts at six-month OCT analysis.

Topics: Acute Coronary Syndrome; Aged; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Single-Blind Method; Sirolimus; Tomography, Optical Coherence

Drug-eluting stents (DES) with durable polymer have significantly reduced restenosis and target vessel revascularization compared with bare metal stents. Durable polymer has been linked with persistent inflammation of vessel wall and delayed endothelial healing that may increase the risk of late and very late stent thrombosis. This study sought to evaluate the efficacy and safety of HELIOS completed biodegradable polymer sirolimus-eluting stent (SES) in de novo coronary lesions.. Totally, 287 patients with one or two de novo coronary lesions (lesion length ≤ 38 mm and reference vessel diameter 2.5-4.0 mm) were enrolled in the HOPE study, a prospective, multicenter, randomized, non-inferiority trial. Patients were randomized to treatment either with HELIOS completed biodegradable polymer SES (n = 142) or PARTNER durable polymer SES (n = 145). The primary endpoint was angiographic in-stent late lumen loss (LLL) at 9-month follow-up. The secondary endpoint included stent thrombosis and major adverse cardiac events including cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR).. The 9-month in-stent LLL in the HELIOS group was similar to the PARTNER group, (0.16 ± 0.22) mm vs. (0.19 ± 0.30) mm (P = 0.28). The difference and 95% confidence interval were -0.03 (-0.09, 0.04), and the P value for non-inferiority <0.01. Major adverse cardiovascular event (MACE) occurred in 7.9% vs. 8.2%, MI in 2.4% vs. 3.0%, TLR in 5.5% vs. 3.0%, and stent thrombosis in 0 vs. 1.5%; and events were comparable between the HELIOS group and PARTNER group at three-year follow-up (all P > 0.05). The three-year cardiac death was lower in the HELIOS group, but with no significant difference, 0 vs. 3.0% (P = 0.12).. In the HOPE trial, the novel completed biodegradable polymer SES HELIOS was non-inferior to the durable polymer SES PARTNER with respect to nine-month in-stent LLL in de novo coronary lesions. The incidence of other clinical endpoints was low for both of the stents in three-year follow-up.

Topics: Adult; Aged; Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Middle Aged; Percutaneous Coronary Intervention; Polymers; Sirolimus; Titanium; Treatment Outcome; Young Adult

To compare the long-term clinical safety between two drug-eluting stents with different healing characteristics in the Patient Related Outcomes with Endeavour (E-ZES) vs. Cypher (C-SES) Stenting Trial (PROTECT). At 3 years, there was no difference in the primary outcome of definite or probable stent thrombosis or in the other main secondary clinical outcomes consisting of the composite of death or myocardial infarction (MI). Prespecified 4-year clinical follow-up was analysed.. Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial was a prospective, open-label randomized-controlled superiority trial powered to look at differences in long-term clinical safety, including stent thrombosis. Dual antiplatelet therapy (DAPT) was prescribed for ≥ 3 months and up to 12 months based on current guidelines. Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial enrolled 8791 patients undergoing elective or emergency PCI to E-ZES or C-SES. There was no difference in DAPT usage between the two groups up to 4 years. At 4-year follow-up, the primary outcome occurred in 1.6% of E-ZES vs. 2.6% of C-SES patients [HR 0.63 (95% CI 0.46-0.85), P = 0.003]. The composite of all-cause death or large MI occurred in 6.7% of E-ZES vs. 8.0% of C-SES-treated patients [HR 0.84 (95% CI 0.71-0.98), P = 0.024].. Drug-eluting coronary stents with different healing characteristics demonstrated different late safety profiles: after 4 years, compared with C-SES, E-ZES reduced the risk of stent thrombosis and the risk of the composite endpoints of death or MI. Appropriately powered large-scale trials with long-term follow-up are critical to determine clinical safety and efficacy of permanently implanted coronary stents. This trial is registered with ClinicalTrials.gov, number NCT00476957.

Topics: Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prosthesis Failure; Sirolimus; Treatment Outcome

This study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI).. There is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age.. In this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow-up as determined by optical coherence tomography.. Men and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up.. In patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207).

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Health Status Disparities; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Prospective Studies; Risk Factors; Rupture, Spontaneous; Sex Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Little is known about the respective healing responses and clinical efficacy and safety of drug-eluting balloons (DEB) and the second generation of drug-eluting stents (DES) when used to treat in-stent restenosis (ISR). In this study, we set out to compare prospectively the healing characteristics, as assessed by optical coherence tomography (OCT), of DEB versus DES after treatment of ISR in bare metal stents (BMS).. Fifty patients with BMS ISR were randomised to treatment with a paclitaxel-eluting balloon vs. an everolimus-eluting stent (EES). The primary endpoint was the percentage of uncovered struts, assessed with OCT at nine months, as a marker of vessel wall healing. A mean of 366±135 and 636±184 struts were analysed per patient in the DEB and EES groups, respectively. The percentage of uncovered struts per patient was significantly lower with DEB vs. EES (1.4% vs. 3.1%, p=0.025). Mean neointimal hyperplasia area was 2.4±1.08 mm in DEB vs. 1.92±0.67 mm in EES (p=0.1806), while the percentage of malapposed struts per patient was very low in both groups (0.2% vs. 0.3%, p=0.699). At nine months, angiographic in-stent MLD (minimum lumen diameter) was lower (2.13 vs. 2.54 mm, p=0.006), while diameter stenosis (26.4 vs. 11.4%, p=0.002), and LLL (0.28 vs. 0.07 mm, p=0.1) were higher after DEB compared to EES. During one-year follow-up, we did not observe differences in the rates of death, TLR (target lesion revascularisation) or stent thrombosis.. DEB appears to be associated with better healing characteristics, as assessed by stent strut coverage with OCT, but tended to be slightly less effective compared to EES. These findings give support to the use of either DEB or EES as valuable treatment options for ISR.. http://www.clinicaltrials.gov. Unique identifier: NCT 01065532.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Paclitaxel; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up.. A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES; P=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm(3) proliferation volume/cm stent length; P=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4; P=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%; P=0.409) was found.. Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up.. http://www.clinicaltrials.gov. Unique identifier: NCT01056744.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Germany; Humans; Male; Metals; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Access Devices

This study sought to investigate the in-scaffold vascular response (SVR) and edge vascular response (EVR) after implantation of an everolimus-eluting bioresorbable scaffold (BRS) using serial optical coherence tomography (OCT) imaging.. Although studies using intravascular ultrasound have evaluated the EVR in metal stents and BRSs, there is a lack of OCT-based SVR and EVR assessment after BRS implantation.. In the ABSORB Cohort B (ABSORB Clinical Investigation, Cohort B) study, 23 patients (23 lesions) in Cohort B1 and 17 patients (18 lesions) in Cohort B2 underwent truly serial OCT examinations at 3 different time points (Cohort B1: post-procedure, 6 months, and 2 years; B2: post-procedure, 1 year, and 3 years) after implantation of an 18-mm scaffold. A frame-by-frame OCT analysis was performed at the 5-mm proximal, 5-mm distal edge, and 2-mm in-scaffold margins, whereas the middle 14-mm in-scaffold segment was analyzed at 1-mm intervals.. The in-scaffold mean luminal area significantly decreased from baseline to 6 months or 1 year (7.22 ± 1.24 mm(2) vs. 6.05 ± 1.38 mm(2) and 7.64 ± 1.19 mm(2) vs. 5.72 ± 0.89 mm(2), respectively; both p < 0.01), but remained unchanged from then onward. In Cohort B1, a significant increase in mean luminal area of the distal edge was observed (5.42 ± 1.81 mm(2) vs. 5.58 ± 1.53 mm(2); p < 0.01), whereas the mean luminal area of the proximal edge remained unchanged at 6 months. In Cohort B2, the mean luminal areas of the proximal and distal edges were significantly smaller than post-procedure measurements at 3 years. The mean luminal area loss at both edges was significantly less than the mean luminal area loss of the in-scaffold segment at both 6-month and 2-year follow-up in Cohort B1 or at 1 year and 3 years in Cohort B2.. This OCT-based serial EVR and SVR evaluation of the Absorb Bioresorbable Vascular Scaffold (Abbott Vascular, Santa Clara, California) showed less luminal loss at the edges than luminal loss within the scaffold. The luminal reduction of both edges is not a nosologic entity, but an EVR in continuity with the SVR, extending from the in-scaffold margin to both edges. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Everolimus; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Patients with coronary total occlusions are at especially high risk for restenosis and new revascularizations. Sirolimus-eluting stents dramatically improved the clinical outcome of this subset of patients in randomized trials, but other drug-eluting stents, mainly the everolimus-eluting stent (currently the most frequently used stent), have not yet been evaluated in patients with coronary total occlusions. The objective was to compare the second-generation everolimus-eluting stent with the first-generation sirolimus-eluting stent in patients with coronary total occlusions.. A total of 207 patients with coronary total occlusions and estimated time since occlusion >2 weeks were randomized to everolimus- or sirolimus-eluting stent. The primary end point was in-stent late loss at 9-month angiographic follow-up (noninferiority trial). Clinical follow-up was performed at 1 and 12 months. In-stent late loss at 9 months was 0.29±0.60 versus 0.13±0.69 mm in patients allocated to sirolimus- and everolimus-eluting stent, respectively. The observed difference in in-stent late loss between both groups was -0.16 mm (95% confidence interval, 0.04 to -0.36 mm; P for noninferiority <0.01). The rate of binary angiographic restenosis was 10.8% and 9.1% in patients allocated to sirolimus- and everolimus-eluting stent, respectively (P=0.709), whereas the rate of vessel reocclusion was 3.2% and 1.1%, respectively (P=0.339). At 12 months, the rate of major adverse events was 15.9% versus 11.1% with sirolimus- and everolimus-eluting stent, respectively (P=0.335), and probable or definitive stent thrombosis occurred in 3.0% and 0.0% of patients, respectively (P=0.075).. In patients with coronary total occlusions, everolimus-eluting stent is as effective as sirolimus-eluting stent.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00793221.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Postoperative Complications; Risk; Sirolimus; Survival Analysis; Treatment Outcome

To analyse the clinical outcome at 4 years in patients with coronary artery disease treated with bare metal stents (BMS) vs. BMS and oral prednisone, or drug-eluting stents (DES), all assuming similar adjunctive medical treatment.. Five Italian hospitals enrolled 375 non-diabetic, ischaemic patients without contraindications to dual anti-platelet treatment or corticosteroid therapy in a randomized controlled study. The primary endpoint was the event-free survival of cardiovascular death, myocardial infarction, and recurrence of ischaemia needing repeated target vessel revascularization at 1 year, and this was significantly lower in the BMS group (80.8%) compared with the prednisone (88.0%) and DES group (88.8%, P = 0.04 and 0.006, respectively). The long-term analysis of the primary endpoint was a pre-specified aim of the trial, and was performed at 1447 days (median, IQ range = 1210-1641). Patients receiving BMS alone had significantly lower event-free survival (75.3%) compared with 84.1% in the prednisone group (HR: 0.447; 95% CI: 0.25-0.80, P = 0.007) and 80.6% in DES patients (HR: 0.519; 95% CI: 0.29-0.93, P = 0.03). Prednisone-treated patients did not develop new treatment-related clinical problems. Drug-eluting stents patients suffered more very late stent thrombosis as a cause of spontaneous myocardial infarction. The need for target vessel revascularization remained lower in the prednisone and DES groups (13.6 and 15.2%, respectively), compared with BMS (23.2%).. The clinical benefits of prednisone compared with BMS only persisted almost unchanged at 4 years. Drug-eluting stents performed better than BMS at long-term, although the advantages observed at 1 year were in part attenuated because of the occurrence of very late stent thrombosis and late revascularizations. Clinical Trial NCT 00369356.

Topics: Administration, Oral; Anti-Inflammatory Agents; Coronary Restenosis; Cortisone; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prednisone; Sirolimus; Treatment Outcome; Tubulin Modulators

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial.

Topics: Antineoplastic Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

This study sought to compare clinical outcomes and angiographic findings using the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Santa Rosa, California) versus the Taxus Liberte paclitaxel-eluting stent (PES) (Boston Scientific, Natick, Massachusetts) in an all-comer Chinese population.. Concerns regarding restenosis risk led to new-generation drug-eluting stents (DES) designed for use in patients with complex clinical or lesion characteristics. In-stent late lumen loss (LLL) is a measure of restenosis risk.. Patients with an indication for treatment with a DES were randomized in a 1:1 ratio to placement of at least 1 R-ZES or PES with minimal exclusions. The primary endpoint was angiographic in-stent LLL at 9 months post-procedure. Clinical endpoints at 12 months are compared between the 2 stents.. A total of 198 patients received a R-ZES, and 202 patients received a PES. Most patients were male; 25.8% and 29.2% of R-ZES and PES patients, respectively, had diabetes. Over 70% of lesions in both cohorts were American College of Cardiology/American Heart Association lesion classification Type B2 and C (B2/C). In-stent LLL was 0.16 ± 0.38 mm for R-ZES and 0.33 ± 0.52 mm for PES at 9 months (p < 0.001; 95% confidence interval [CI]: -0.26 to -0.08). The rates of clinically driven target lesion revascularization were 1.5% for R-ZES and 7.0% for PES (p = 0.011). The rate of target lesion failure was 5.6% for R-ZES and 11% for PES (p = 0.068).. In an all-comers Chinese population, 9-month in-stent LLL was significantly less with R-ZES compared with PES, which was reflected in lower revascularization rates at 12 months for the R-ZES patients. Results are consistent with previous clinical trials of the R-ZES in all-comer populations. (Resolute Zotarolimus-Eluting Stent Versus the Taxus Liberte Paclitaxel-Eluting Stent for Percutaneous Coronary Intervention in China [R-China RCT]; NCT01334268).

Topics: Aged; Cardiovascular Agents; China; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

This study sought to compare the efficacy and safety results after coronary implantation of a combined sirolimus-eluting CD34 antibody coated Combo stent (OrbusNeich Medical, Ft. Lauderdale, Florida) with the paclitaxel-eluting Taxus Liberté stent (PES) (Boston Scientific, Natick, Massachusetts). This report summarizes the first-in-man randomized, controlled multicenter REMEDEE trial (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) angiographic, intravascular ultrasound, and clinical results up to 12 months.. Drug-eluting stents have limited restenosis and reintervention but are complicated by especially late and very late stent thrombosis and accelerated neoatherosclerosis. Alternative or adjunct technologies should address these limitations.. One hundred eighty-three patients with de novo native coronary artery stenoses were randomized 2:1 to Combo stent or PES implantation. The primary endpoint is the angiographic in-stent late lumen loss at 9 months, which was tested for noninferiority between the 2 stent groups. Secondary endpoints include the occurrence of major adverse cardiac events.. The Combo stent was found to be noninferior to the PES in 9-month angiographic in-stent late lumen loss with 0.39 ± 0.45 mm versus 0.44 ± 0.56 mm (pnoninferiority = 0.0012). At 12 months, the occurrence of major adverse cardiac events was 8.9% in the Combo group and 10.2% in the PES group (p = 0.80) with no difference in mortality, occurrence of myocardial infarction, or target lesion revascularization. No stent thrombosis was reported in either group.. In the REMEDEE trial the Combo stent has shown to be effective by meeting the primary noninferiority angiographic endpoint and safe, with an overall low rate of clinical events in both stent groups, including no stent thrombosis up to 12 months.

Topics: Aged; Antibodies; Antigens, CD34; Asia; Australia; Brazil; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Endothelial Cells; Europe; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Sirolimus; Stem Cells; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The cobalt chromium everolimus-eluting stent (CoCr-EES) has shown the best safety and efficacy profile in the trials conducted so far. Recently, a new EES with a platinum-based platform (PtCr-EES) has been introduced in the market. There is only one study comparing both stents, but with important exclusion criteria.. We sought to evaluate clinical outcomes with the PtCr-EES compared with the CoCr-EES in an all-comers population. We have conducted a randomized all-comers study aimed to compare these stents in a real-practice scenario.. A total of 300 patients undergoing revascularization and suitable for long-term dual-antiplatelet therapy were randomized 1:1 to CoCr-EES or PtCr-EES. No exclusion criteria based on clinical presentation or lesion characteristics were applied.. The clinical and angiographic characteristics were well balanced in both groups without significant differences. At 18 months, the survival free from death and infarction was 93.9% for CoCr-EES and 91.3% for PtCr-EES (P=.3), the survival free from revascularization was 95.2% vs 94.5% (P=.6) and the survival free from death, infarction, and revascularization was 90.6% vs 88%, respectively (P=.4). The incidence of definite or probable thrombosis was 1.3% for CoCr-EES and 0.66% for PtCr-EES (P=.9). No cases of longitudinal stent compression were observed.. The results of this all-comers trial do not show significant differences between CoCr-EES and PtCr-EES. However, the sample size is not powered to exclude potential differences between stents.

Topics: Aged; Angina, Stable; Angina, Unstable; Chromium Alloys; Coronary Restenosis; Drug-Eluting Stents; Equipment Failure; Everolimus; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platinum; Sirolimus; Thrombosis; Treatment Outcome

The ZOMAXX I trial tested the noninferiority of a zotarolimus-eluting coronary stent (ZoMaxx(™) ) when compared with a paclitaxel-eluting coronary stent (Taxus(™) Express(2™) ) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. Angiographic analysis at the primary endpoint of 9 months has been reported previously. The purpose of this follow-on analysis was to describe the clinical results of the ZoMaxx and Taxus cohorts of the ZOMAXX I trial after 5 years.. In the ZOMAXX I trial, 199 patients received a ZoMaxx stent and 197 patients received a Taxus stent at 29 investigative sites in Europe, Australia, and New Zealand. The two groups were generally well matched with respect to both clinical and lesional characteristics, including the incidence of diabetes (ZoMaxx 22% vs. Taxus 26%; P = 0.29), reference vessel diameter (ZoMaxx 2.79 ± 0.43 mm vs. Taxus 2.81 ± 0.46 mm; P = 0.65), and lesion length (ZoMaxx 14.9 ± 5.7 mm vs. Taxus 14.6 ± 5.5; P = 0.61). Through 5 years of follow-up, a total of 21 patients had died, six patients had withdrawn, nine had been lost to follow-up, and 13 missed their 5-year visit, leaving a total of 347 patients for analysis (169 ZoMaxx and 178 Taxus). At the 5-year time point, there were no significant differences in any clinical metric including ischemia-driven target lesion revascularization (TLR; ZoMaxx 10.6% vs. Taxus 7.1%; P = 0.29), Q-wave myocardial infarction (ZoMaxx 1.5% vs. Taxus 1.0%; P = 0.99), definite/probable stent thrombosis (ZoMaxx 1.5% vs. Taxus 3.0%; P = 0.34), and cardiac death (ZoMaxx 3.0% vs. Taxus 1.0%; P = 0.28).. After 5 years, the differences in clinical outcome between patients treated with ZoMaxx vs. Taxus stents did not reach statistical significance. However, the nominally higher rate of ischemia-driven TLR (10.6 vs. 7.1%) and the previously reported higher rate of restenosis after 9 months suggest that the ZoMaxx stent afforded less neointimal inhibition when compared with Taxus. © 2013 Wiley Periodicals, Inc.

Topics: Aged; Australia; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Europe; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; New Zealand; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

The aim of this study was to evaluate late safety and efficacy outcomes among patients enrolled in clinical trials comparing Endeavor zotarolimus-eluting stents (E-ZES) (Medtronic, Inc., Santa Rosa, California) with first-generation drug-eluting stents (DES) and bare-metal stents (BMS).. Despite demonstration of higher angiographic luminal loss and restenosis with E-ZES compared with alternative DES, whether differences in these early angiographic measures translate into more disparate late clinical events is uncertain.. Among 3,616 patients undergoing percutaneous coronary revascularization in 5 registration trials, late safety and efficacy events were compared between E-ZES (n = 2,132) versus sirolimus- or paclitaxel-eluting stents (n = 888) or BMS (n = 596).. Compared with a parallel cohort of patients treated with first-generation DES and BMS, 5-year rates of cardiac death/myocardial infarction (MI) (5.8% vs. 8.8% DES, p = 0.003; vs. 8.4% BMS, p = 0.02) and major adverse cardiac events (16.1% vs. 20.6% DES, p = 0.009; vs. 24.6% BMS, p < 0.001) were significantly lower with E-ZES. The E-ZES was associated with significantly lower target lesion revascularization (TLR) compared with BMS (7.4% vs. 16.3%, p < 0.001) but similar to comparator DES (7.4% vs. 8.1%, p = 0.63). Despite higher TLR in the first year with E-ZES compared with DES, between 1- and 5-year follow-up, rates of cardiac death/MI, TLR, and definite/probable stent thrombosis were significantly lower with E-ZES.. Over 5 years, significant differences in cardiac death/MI and composite endpoints favored treatment with E-ZES over comparator BMS and DES. Rates of clinical restenosis and safety events, including stent thrombosis beyond the first year of revascularization, remain stable with E-ZES, leading to significant differences compared with first-generation DES.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome

Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar clinical outcomes. This study was aimed to clarify the differences in the angiographic findings of EES as compared to SES. Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. From February to July 2010, 3197 patients were randomly assigned to receive either EES or SES. Of these, angiographic sub-study enrolled 571 patients (EES 285 patients, SES 286 patients). Angiograms were assessed qualitatively and quantitatively at procedure and at 8-12 months in the independent core angiographic laboratory. Late loss of the proximal edges tended to be greater in the EES group than that in the SES group (0.12 ± 0.49 vs. 0.04 ± 0.43 mm, P = 0.05), although late loss in the other segments was similar between the 2 groups. Edge restenosis was mainly observed in EES group, whereas body restenosis was demonstrated in half of SES group. Stent fracture was observed only in the SES group (1.5 %), and peri-stent contrast staining (PSS) tended to be more frequently observed in the SES group than in the EES group (3.6 and 1.5 %, P = 0.18). Restenotic response in the proximal edge was more prominent in the EES group as compared to the SES group. Abnormal angiographic findings such as stent fracture and PSS tended to be more frequent in the SES group.

Topics: Aged; Aged, 80 and over; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Japan; Male; Middle Aged; Prospective Studies; Sirolimus; Treatment Outcome

The study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) for treating patients with single de novo coronary lesions compared with the durable polymer everolimus-eluting stent (EES) XIENCE V.. A total of 458 patients with single de novo native coronary lesions ≤24 mm in length and a coronary artery ≥2.25 to ≤4.0 mm in diameter were enrolled in the TARGET I study, a prospective, randomised, non-inferiority trial. The primary endpoint was in-stent late lumen loss (LLL) at nine-month follow-up. The secondary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, target vessel myocardial infarction (TVMI), or ischaemia-driven target lesion revascularisation (iTLR). Patients were centrally randomised to treatment with either biodegradable polymer SES (n=227) or durable polymer EES (n=231). The nine-month in-stent LLL of the biodegradable polymer SES was comparable to the EES group (0.13 ± 0.24 mm vs. 0.13 ± 0.18 mm, p=0.94; difference and 95% confidence interval 0.00 [-0.04, 0.04] mm; p for non-inferiority <0.0001). Cardiac death (0.4% vs. 0.0%), TVMI (1.3% vs. 1.7%), iTLR (0.4% vs. 0.4%) and TLF (2.2% vs. 2.2%) were similar between the biodegradable polymer SES and durable polymer EES groups at 12-month follow-up (all p>0.05). No definite/probable stent thrombosis was observed in both of these groups.. In the multicentre TARGET I trial, the novel abluminal groove-filled biodegradable polymer SES FIREHAWK was non-inferior to the durable polymer EES XIENCE V with respect to the primary endpoint of in-stent LLL at nine months for treating patients with single de novo coronary lesions. The incidences of clinical endpoints were low in both of the stents at 12-month follow-up. (ClinicalTrials.gov identifier: NCT01196819).

Topics: Absorbable Implants; Aged; Analysis of Variance; Antineoplastic Agents; Chi-Square Distribution; China; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

Intravascular ultrasound (IVUS) offers tomographic images of the coronary artery, helping physicians to refine drug-eluting stent (DES) implantation in angiographically complex lesions. However, controversy exists regarding whether the routine use of IVUS in short-length lesions leads to improved clinical outcomes after DES implantation. Therefore, we evaluated the usefulness of IVUS in predicting major adverse cardiac events (MACE), including cardiovascular death, myocardial infarction, or target vessel revascularization, at 1 year after DES implantation in short-length lesions. The present study was a subanalysis of the REal Safety and Efficacy of a 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation (RESET) study with different clinical outcome parameters. The study population consisted of 662 patients with IVUS guidance and 912 patients with angiography guidance who underwent DES implantation (stent length ≤24 mm). In the IVUS-guided group, adjuvant postdilation was more frequently performed (43.0% vs 34.6%, p <0.001), and the postintervention minimal lumen diameters were greater (2.88 ± 0.44 mm vs 2.72 ± 0.43 mm, p <0.001). MACE occurred in 15 IVUS-guided (2.3%) and 19 angiographically guided (2.1%) patients (p = 0.872). In a subset of patients with diabetes mellitus (n = 292), the MACE rate was 3.4% (n = 4) and 1.7% (n = 3) in the IVUS- and angiographically guided patients, respectively (p = 0.384). The MACE rate in the IVUS- and angiographically guided patients with acute coronary syndrome (n = 601) was 1.1% (n = 3) and 2.7% (n = 9), respectively (p = 0.194). The clinical benefits of IVUS-guided DES implantation compared with angiographically guided DES implantation in short-length lesions could not be confirmed even in patients with clinically high-risk presentations (acute coronary syndrome and diabetes mellitus). In conclusion, routine IVUS guidance does not provide clinical benefits when performing short-length DES implantation.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prognosis; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

To assess long-term outcomes of Endeavor Zotarolimus-eluting stent (E-ZES) implantation in patients with diabetes mellitus (DM).. Patients with DM and coronary artery disease have lower restenosis with drug-eluting stent (DES) compared with bare-metal stents. Recent data suggest that the E-ZES is inferior to other DES in this population.. Patient-level data for 601 patients with DM from the ENDEAVOR III and ENDEAVOR IV trials were pooled, of which 337 were treated with E-ZES and 264 were treated with other DES. The primary outcome was target vessel failure (TVF) in the course of 5 years. Outcomes are reported as rates using Kaplan-Meier (KM) survival method and differences between E-ZES and other stent types (sirolimus-eluting stent or paclitaxel-eluting stent) were compared using the log-rank statistic. The independent effect of stent type on TVF was assessed using Cox proportional hazards regression.. Baseline characteristics were similar between the groups. Five-year TVF KM rate estimate was numerically lower for E-ZES, but the difference did not reach statistical significance (20.2 vs. 26.9%, P = 0.065). The 5-year KM rate estimates of major adverse cardiac events (17.7 vs. 26.6%, P = 0.012), death (7.6 vs. 15.0%, P = 0.004), and myocardial infarction (1.3 vs. 5.1%, P = 0.011) were also lower for E-ZES versus other DES.. Patients with DM implanted with E-ZES have favorable long-term outcomes compared to first-generation DES. Long-term performance of DES should be assessed routinely and may differ from initial performance.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Histologic experimental studies have reported incomplete neointimal healing in overlapping with respect to nonoverlapping segments in drug-eluting stents (DESs), but these observations have not been confirmed in human coronary arteries hitherto. On the contrary, angiographic and optical coherence tomography studies suggest that DES overlap elicits rather an exaggerated than an incomplete neointimal reaction.. Optical coherence tomography studies from 2 randomized trials including sirolimus-eluting, biolimus-eluting, everolimus-eluting, and zotarolimus-eluting stents were analyzed at 9- to 13-month follow-up. Coverage in overlapping segments was compared versus the corresponding nonoverlapping segments of the same stents, using statistical pooled analysis.. Forty-two overlaps were found in 31 patients: 11 in sirolimus-eluting stents, 3 in biolimus-eluting stents, 17 in everolimus-eluting stents, and 11 in zotarolimus-eluting stents. The risk ratio of incomplete coverage was 2.35 (95% CI 1.86-2.98) in overlapping versus nonoverlapping segments. Thickness of coverage in overlaps was only 85% (95% CI 81%-90%) of the thickness in nonoverlaps. Significant heterogeneity of the effect was observed, especially pronounced in the comparison of thickness of coverage (I(2) = 90.31).. The effect of overlapping DES on neointimal inhibition is markedly heterogeneous: on average, DES overlap is associated with more incomplete and thinner coverage, but in some cases, the overlap elicits an exaggerated neointimal reaction, thicker than in the corresponding nonoverlapping segments. These results might help to understand why overlapping DES is associated with worse clinical outcomes, both in terms of thrombotic phenomena and in terms of restenosis and revascularization.

Topics: Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Feasibility Studies; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Neointima; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The EVOLVE FHU trial demonstrated non-inferiority of six-month late loss with two dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus-eluting stent (EES) compared with the durable polymer PROMUS Element (PE) EES. The current analysis describes the six-month IVUS and clinical results through two years from the EVOLVE FHU trial.. EVOLVE recruited 291 patients from 29 centres. At six months, IVUS-assessed in-stent net volume obstruction was 3.40 ± 5.06% for PROMUS Element (PE) vs. 2.68 ± 4.60% for SYNERGY (p=0.34) and 3.09 ± 4.29% for SYNERGY ½ dose (p=0.68 vs. PE). There were no significant differences between groups for any other measured IVUS parameter including resolved, persistent, and late-acquired incomplete stent apposition (ISA). At two years, target lesion failure (TLF) was 6.1% for PE vs. 5.5% for SYNERGY (p=0.87) and 5.2% for SYNERGY ½ dose (p=0.81). There were no significant differences between groups for cardiac death, repeat revascularisation, MI or stent thrombosis through two years.. At six months, everolimus delivered from an ultrathin bioabsorbable abluminal polymer resulted in equivalent net volume obstruction and ISA compared with a permanent polymer EES. There were no significant differences between PE and either SYNERGY stent for any major cardiac endpoint through two years. Clinical trials number: NCT01135225.

Topics: Australia; Cardiovascular Agents; Chi-Square Distribution; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Humans; Kaplan-Meier Estimate; Myocardial Infarction; New Zealand; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

We report the initial human evaluation of the novel BioMimeTM sirolimus-eluting stent (SES) (Meril Life Sciences Pvt. Ltd., Gujarat, India) with an ultra-thin stent platform (65 μm) and a biodegradable polymer for the treatment of de novo coronary lesions.. The meriT-1 trial was a prospective, non-randomised, single-arm, single-centre, first-in-human evaluation of the safety, feasibility and performance of the BioMime SES. Lesion criteria included non-occlusive stenosis ≤ 19 mm in length located in native coronary vessels. Clinical follow-up (FU) was performed at 1, 8 and 12 months; all patients were assigned for angiographic FU at eight months. A total of 30 patients (30 lesions) were enrolled between March 2009 and February 2010. Mean age was 49.9 years, 30% were diabetics, and 36.7% had previous myocardial infarction (MI). Baseline median [25%, 75% interquartile range] lesion length, reference diameter and % diameter stenosis were 15.51 mm [12.74, 20.27], 2.94 mm [2.71, 3.34], and 80.5% [67.0%, 90.7%], respectively. Overall, there was one stent implanted per lesion and procedural success was 100%. At eight-month angiographic FU (26/30), median in-stent late lumen loss was 0.15 mm [0.09, 0.33]; also, there were no cases of binary restenosis within the treated segment. Clinical FU at 12 months (100%) demonstrated absence of MACE (cardiac death, MI and target lesion revascularisation) and stent thrombosis (ST).. The novel BioMime SES demonstrated excellent performance in single coronary lesions including high procedural success and efficacy, as demonstrated by the relatively low late lumen loss (a surrogate of neointimal hyperplasia) at eight-month angiographic FU. Overall, there were no safety concerns in this preliminary evaluation including absence of MACE or ST up to 12 months.

Topics: Adult; Aged; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Polymers; Prospective Studies; Sirolimus; Treatment Outcome

This study sought to compare the safety and efficacy of the zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES) for treatment of unprotected left main coronary artery (uLMCA) disease.. The second-generation ZES and EES have reduced the risk of restenosis in large patient cohorts. However, their comparative performance in uLMCA lesions is not known.. In this study, patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention for uLMCA lesions were randomly assigned to receive either a ZES (n = 324) or an EES (n = 326). The primary endpoint was the combined incidence of death, myocardial infarction, and target lesion revascularization at 1 year. Secondary endpoints were definite or probable stent thrombosis at 1 year and angiographic restenosis based on analysis of the left main coronary artery area at follow-up angiography.. At 1 year, the cumulative incidence of the primary endpoint was 17.5% in the ZES group and 14.3% in the EES group (relative risk: 1.26; 95% confidence interval [CI]: 0.85 to 1.85; p = 0.25). Three patients in the ZES group (0.9%) and 2 patients in the EES group (0.6%) experienced definite or probable stent thrombosis (p > 0.99). All-cause mortality at 1 year was equal in the 2 groups (5.6%; relative risk: 1.00; 95% CI: 0.52 to 1.93; p = 0.98). Angiographic restenosis occurred in 21.5% of patients in the ZES group and 16.8% in the EES group (relative risk: 1.28; 95% CI: 0.86 to 1.92; p = 0.24).. Within the statistical limitations of the present study, treatment of uLMCA lesions with a ZES or an EES provided comparable clinical and angiographic outcomes at 1-year follow-up.

Topics: Aged; Aged, 80 and over; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Middle Aged; Myocardial Infarction; Sirolimus

This first-in-human multicenter study sought to examine prospectively the safety and efficacy of a new, cobalt chromium thin-strut, coronary absorbable polymer-coated, sirolimus-eluting stent.. Bioabsorbable polymers on drug-eluting stents may lower the long-term risks of inflammation, delayed healing, and adverse events.. We enrolled patients with symptomatic coronary artery disease with stable or unstable angina pectoris and >50% diameter stenosis, amenable to coverage with a ≤23-mm long stent in a vessel 2.5 to 3.5 mm in diameter. All patients received dual antiplatelet therapy after implantation. Patients, in groups of 10, underwent repeat angiography, intravascular ultrasound, and optical coherence tomography at 4, 6, or 8 months, and all patients were seen or contacted at 18 months of follow-up.. The median (range) in-stent late lumen loss (LLL) was 0.03 mm (-0.22 to 0.21 mm), 0.10 mm (-0.03 to 1.2 mm), and 0.08 mm (-0.01 to 0.28 mm), at 4, 6, and 8 months, respectively. At 18 months, the median in-stent LLL was 0.08 mm (-0.30 to 0.46 mm). On optical coherence tomography, the proportion of uncovered stent struts decreased from a median of 7.3% (range 0.4% to 46.3%) at 4 months to 0% (range: 0% to 3.4%) at 18 months. The percentage of neointimal volume obstruction by intravascular ultrasound increased from a median of 5.3% to 9.1% between 4 and 6 months and remained nearly unchanged thereafter through 18 months of follow-up. The only recorded major adverse cardiac event was a myocardial infarction.. At 18 months of follow-up, this absorbable polymer-coated, cobalt chromium sirolimus-eluting stent was associated with a low and stable in-stent LLL, complete strut coverage, and no stent thrombosis. (First-In-Human Trial of the MiStent Drug-Eluting Stent [DES] in Coronary Artery Disease [DESSOLVE-I]; NCT01247428).

Topics: Absorbable Implants; Adult; Aged; Aged, 80 and over; Angina, Stable; Angina, Unstable; Australia; Belgium; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; New Zealand; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Prospective Studies; Prosthesis Design; Severity of Illness Index; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

This study sought to investigate the efficacy and performance of the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary lesions in patients with 2- to 3-vessel multivessel coronary artery disease (MV-CAD).. Drug-eluting stents (DES) have emerged as an alternative to conventional coronary artery bypass surgery in patients with MV-CAD although first-generation DES yielded inferior efficacy and safety compared with surgery.. Prospective, randomized (1:1), multicenter feasibility trial was designed to assess angiographic efficacy of EES compared with the TAXUS paclitaxel-eluting stent (PES) in 200 patients, and a prospective, open-label, single-arm, controlled registry was designed to analyze the clinical outcome of EES at 1-year follow-up in 400 MV-CAD patients. For the randomized trial, the primary endpoint was in-stent late loss at 9 months. For the registry, the primary endpoint was a composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization at 12 months.. The primary endpoint per single lesion was significantly lower in the EES group compared with the PES group (-0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed when analyzing all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001). Clinical outcome at 1 year yielded a composite of major adverse cardiac events of 9.2% in the single-arm registry, and 11.1% and 16.5% in the EES and PES randomized groups, respectively (p = 0.30).. The EXECUTIVE trial was a randomized pilot trial dedicated to the comparison of the efficacy of 2 different DES among patients with 2- to 3-vessel MV-CAD. The study shows lower in-stent late loss at 9 months with the EES XIENCE V compared with the PES TAXUS Libertè, and a low major adverse cardiac event rate at 1 year in patients with 2-to 3-vessel MV-CAD. (EXECUTIVE [EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease]; NCT00531011).

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Feasibility Studies; Female; Humans; Italy; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Sirolimus; Time Factors; Treatment Outcome

Small vessels represent a risk factor for restenosis in percutaneous coronary angioplasty (PCA). The Sparrow® self-expanding drug-eluting stent, which has a lower profile than the current systems, has never been tested in this scenario.. To evaluate the late effectiveness of the Sparrow® drug-eluting stent, regarding in-stent late lumen loss (LLL).. Patients with ischemia, symptomatic or documented, were submitted to PCA in vessels with reference diameter < 2.75 mm, divided into two groups regarding Sparrow® stent type: group 1: Sparrow® drug-eluting stent (DES), group 2: Sparrow® bare metal stent (BMS). Clinical follow-up duration was 12 months. Evaluation using quantitative coronary angiography (QCA) was performed immediately and at 8 months. A decrease of over 65% of in-stent LLL with DES was estimated to calculate sample size. IBM® SPSS software, release 19 (Chicago, Illinois, USA) was used for the statistical analysis.. A total of 24 patients were randomized, 12 in each group. The DES and BMS groups were similar in age (63.25 ± 10.01 vs. 64.58 ± 11.54, p = 0.765), male gender (58.3% vs. 33.3%, p = 0.412), risk factors and all angiographs aspects. Immediate results were satisfactory in both groups. At 8 months in-stent late lumen loss was significantly lower in DES than in BMS group (DES vs. BMS 0.25 ± 0.16 0.97 ± 0.76, p = 0.008).. In small-vessel PCA, the Sparrow® DES determined significant reduction in in-stent LLL, when compared to Sparrow® BMS.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Miniaturization; Sirolimus; Stents; Treatment Outcome

This study sought to demonstrate the 5-year clinical and functional multislice computed tomography angiographic results after implantation of the fully resorbable everolimus-eluting scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California).. Multimodality imaging of the first-in-humans trial using a ABSORB BVS scaffold demonstrated at 2 years the bioresorption of the device while preventing restenosis. However, the long-term safety and efficacy of this therapy remain to be documented.. In the ABSORB cohort A trial (ABSORB Clinical Investigation, Cohort A [ABSORB A] Everolimus-Eluting Coronary Stent System Clinical Investigation), 30 patients with a single de novo coronary artery lesion were treated with the fully resorbable everolimus-eluting Absorb scaffold at 4 centers. As an optional investigation in 3 of the 4 centers, the patients underwent multislice computed tomography (MSCT) angiography at 18 months and 5 years. Acquired MSCT data were analyzed at an independent core laboratory (Cardialysis, Rotterdam, the Netherlands) for quantitative analysis of lumen dimensions and was further processed for calculation of fractional flow reserve (FFR) at another independent core laboratory (Heart Flow, Redwood City, California).. Five-year clinical follow-up is available for 29 patients. One patient withdrew consent after 6 months, but the vital status of this patient remains available. At 46 days, 1 patient experienced a single episode of chest pain and underwent a target lesion revascularization with a slight troponin increase after the procedure. At 5 years, the ischemia-driven major adverse cardiac event rate of 3.4% remained unchanged. Clopidogrel was discontinued in all but 1 patient. Scaffold thrombosis was not observed in any patient. Two noncardiac deaths were reported, 1 caused by duodenal perforation and the other from Hodgkin's disease. At 5 years, 18 patients underwent MSCT angiography. All scaffolds were patent, with a median minimal lumen area of 3.25 mm(2) (interquartile range: 2.20 to 4.30). Noninvasive FFR analysis was feasible in 13 of 18 scans, which yielded a median distal FFR of 0.86 (interquartile range: 0.82 to 0.94).. The low event rate at 5 years suggests sustained safety after the implantation of a fully bioresorbable Absorb everolimus-eluting scaffold. Noninvasive assessment of the coronary artery with an option of functional assessment could be an alternative to invasive imaging after treatment of coronary narrowing with such a polymeric bioresorbable scaffold. (ABSORB Clinical Investigation, Cohort A [ABSORB A] Everolimus-Eluting Coronary Stent System Clinical Investigation [ABSORB]; NCT00300131).

Topics: Aged; Biocompatible Materials; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Female; Fractional Flow Reserve, Myocardial; Humans; Male; Middle Aged; Multidetector Computed Tomography; New Zealand; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

Paclitaxel-eluting balloons (PEBs) are a promising alternative to drug-eluting stent (DES) in the treatment of coronary stenoses. The aim of our study was to compare the 9-month restenosis rates of a strategy of predilatation with PEB followed by bare-metal CoCr stent (PEB + BMS group) versus implantation of everolimus DES (DES group).. This randomized, single-center study planned to enroll 366 patients with stable angina (183 patients per arm) undergoing percutaneous coronary intervention of a de novo, native coronary artery stenosis ≤ 15 mm in length. Primary end point, in a noninferiority study design, was 9-month binary angiographic restenosis. A frequency-domain optical coherence tomography substudy investigated the percentage of uncovered stent struts per lesion, the percentage of malapposed/uncovered struts per lesion, and the percentage of net volume obstruction at 9-month follow-up among the first consecutive 30 patients enrolled in the PEB + BMS group.. The study was prematurely halted after enrollment of 125 patients, 59 in the PEB + BMS group and 66 in the DES group, because of excess of ischemia-driven target lesion revascularization in the PEB + BMS group. When all the enrolled patients completed their follow-up, IDLTR rates were 14% in the PEB + BMS versus 2% in DES group (P = .001). Binary restenosis, either in-stent or in-segment, was significantly higher in the PEB + BMS compared with DES group (17% vs 3% [P = .01] and 25% vs 4% [P = .009] respectively). Frequency-domain optical coherence tomography demonstrated important neointimal regrowth in the PEB + BMS group, similar to historical BMS data.. In the treatment of de novo coronary stenosis, a strategy of predilatation with PEB before BMS implantation was significantly inferior to implantation of an everolimus DES stent in terms of 9-month target lesion revascularization. Frequency-domain optical coherence tomography data confirm the lack of efficacy of this strategy.

Topics: Aged; Aged, 80 and over; Angina, Stable; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

This study sought to evaluate the long-term safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in patients with obstructive coronary artery disease.. The use of EES compared to PES has been shown to result in improved clinical outcomes in patients undergoing PCI. However, there have been concerns regarding the durability of these benefits over longer-term follow-up.. SPIRIT III was a prospective, multicenter trial in which 1,002 patients were randomized 2:1 to EES versus PES. Endpoints included ischemia-driven target vessel failure (TVF) (death, myocardial infarction (MI), or ischemia-driven target vessel revascularization [TVR]), the pre-specified primary endpoint), target lesion failure (TLF) (cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization [TLR]), major adverse cardiac events (MACE) (cardiac death, MI, or ischemia-driven TLR), their individual components and stent thrombosis.. Five-year follow-up was available in 91.9% of patients. Treatment with EES versus PES resulted in lower 5-year Kaplan-Meier rates of TVF (19.3% vs. 24.5%, p = 0.05), TLF (12.7% vs. 19.0%, p = 0.008), and MACE (13.2% vs. 20.7%, p = 0.007). EES also resulted in reduced rates of all-cause death (5.9% vs. 10.1%, p = 0.02), with nonsignificantly different rates of MI, stent thrombosis, and TLR, and no evidence of late catch-up of TLR over time.. At 5 years after treatment, EES compared to PES resulted in durable benefits in composite safety and efficacy measures as well as all-cause mortality. Additionally, the absolute difference in TLR between devices remained stable over time without deterioration of effect during late follow-up.

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Kaplan-Meier Estimate; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome; United States

The Orsiro Hybrid sirolimus-eluting stent is a newly developed third-generation drug-eluting stent, featuring a unique dual-polymer mix. An active bioabsorbable polymer delivers the anti-proliferative drug, sirolimus, via controlled release, while a passive biocompatible polymeric coating shields the metallic strut from surrounding tissue, preventing interaction. To date, the Orsiro Hybrid sirolimus-eluting stent has excelled in terms of late lumen loss at 9 months in a first-in-man single-arm trial. However, the efficacy and safety data for Orsiro Hybrid sirolimus-eluting stents in a broader population of all-comers are limited. The present study offers an angiographic and clinical comparison of the Orsiro Hybrid sirolimus-eluting stent and the Resolute Integrity zotarolimus-eluting stent in the treatment of patients with coronary artery disease.. The ORIENT trial is a multicenter, randomized, open-label, parallel-arm study designed to demonstrate the non-inferiority of the Orsiro Hybrid sirolimus-eluting stent relative to the Resolute Integrity zotarolimus-eluting stent. A total of 375 patients with a spectrum of coronary artery disease will undergo prospective, random assignment to a Orsiro Hybrid sirolimus-eluting stent or Resolute Integrity zotarolimus-eluting stent (2:1 ratio), for a primary endpoint of in-stent late lumen loss at 9 months by quantitative coronary angiography. Secondary 12-month clinical endpoints are death, target lesion revascularization, target vessel revascularization, myocardial infarction, stent thrombosis and target lesion failure (a composite of cardiac death, target lesion revascularization and target vessel-related myocardial infarction).. The ORIENT trial is the first study to date comparing the Orsiro Hybrid sirolimus-eluting stent with the Resolute Integrity zotarolimus-eluting stent for efficacy and safety in a population of all-comers with coronary artery disease.. Clinicaltrials.gov NCT01826552.

Topics: Cardiovascular Agents; Clinical Protocols; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Republic of Korea; Research Design; Sirolimus; Time Factors; Treatment Outcome

The aim of the study was to compare long-term follow-up results of crush versus culotte stent techniques in coronary bifurcation lesions.. The randomized Nordic Stent Technique Study showed similar 6-month clinical and 8-month angiographic results with the crush and culotte stent techniques of de novo coronary artery bifurcation lesions using sirolimus-eluting stents. Here, we report the 36-month efficacy and safety of the Nordic Stent Technique Study.. A total of 424 patients with a bifurcation lesion were randomized to stenting of both main vessel and side branch with the crush or the culotte technique and followed for 36 months. Major adverse cardiac events-the composite of cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization-were the primary endpoint.. Follow-up was complete for all patients. At 36 months, the rates of the primary endpoint were 20.6% versus 16.7% (p = 0.32), index lesion restenosis 11.5% versus 6.5% (p = 0.09), and definite stent thrombosis 1.4% versus 4.7% (p = 0.09) in the crush and the culotte groups, respectively.. At 36-month follow-up, the clinical outcomes were similar for patients with coronary bifurcation lesions treated with the culotte or the crush stent technique. (Nordic Bifurcation Study. How to Use Drug Eluting Stents [DES] in Bifurcation Lesions? NCT00376571).

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Finland; Humans; Latvia; Male; Middle Aged; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Scandinavian and Nordic Countries; Sirolimus; Time Factors; Treatment Outcome

We aimed comparing two-year clinical outcomes of the Everolimus-Eluting Promus and Paclitaxel-Eluting TAXUS Liberte stents used in routine clinical practice. Patients with objective evidence of ischemia and coronary artery disease eligible for PCI were prospectively randomized to everolimus-eluting stent (EES) or paclitaxel-eluting stent (PES) groups. The primary end-point was ischemia-driven target vessel revascularization (TVR) at 2 yr after intervention, and the secondary end-point was a major adverse cardiac event (MACE), such as death, myocardial infarction (MI), target lesion revascularization (TLR), TVR or stent thrombosis. A total of 850 patients with 1,039 lesions was randomized to the EES (n=425) and PES (n=425) groups. Ischemic-driven TVR at 2 yr was 3.8% in the PES and 1.2% in the EES group (P for non-inferiority=0.021). MACE rates were significantly different; 5.6% in PES and 2.5% in EES (P = 0.027). Rates of MI (0.8% in PES vs 0.2% in EES, P = 0.308), all deaths (1.5% in PES vs 1.2% in EES, P = 0.739) and stent thrombosis (0.3% in PES vs 0.7% in EES, P = 0.325) were similar. The clinical outcomes of EES are superior to PES, mainly due to a reduction in the rate of ischemia-driven TVR.

Topics: Antineoplastic Agents, Phytogenic; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Thrombosis; Treatment Outcome

Coronary bifurcation lesions can be approached using a simple or a complex strategy. In clinical trials with first-generation drug-eluting stents, the complex strategy was not superior to the simple approach. However, to date, the best strategy when using second-generation drug-eluting stents has not been defined.. We performed a prospective randomized study comparing a simple vs a complex strategy involving T-stenting for the percutaneous revascularization of bifurcation lesions using the everolimus-eluting stent. Angiographic and clinical follow-up were performed at 9 months.. We included 70 lesions in 69 patients, who were randomized to the simple (34 lesions, 33 patients) or complex strategy (36 lesions and patients). In all, 85.6% of the lesions included were true bifurcations. The crossover rate was 17.1%. The binary restenosis rate was 12.1%, with no differences between the groups. Side branch restenosis tended to be higher with the simple strategy in the intention to treat analysis (10.7% vs 0%) but not in the per protocol analysis (5.9% vs 4.2%). The incidence of major adverse cardiac events (cardiac death, myocardial infarction, and target vessel revascularization) was 9.2%, with no differences between groups. There were no cases of stent thrombosis.. According to the clinical and angiographic findings, the complex strategy was not significantly superior to the simple approach in the revascularization of bifurcation lesions with second-generation everolimus-drug eluting stents.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus

Limited evidence exists regarding the long-term performance of polymer-free (PF) drug-eluting stents (DES) in comparison to permanent polymer DES. This study investigated the 5-year efficacy and safety of a PF sirolimus-eluting stent (PF-SES) versus a permanent polymer paclitaxel-eluting stent (PES) in the setting of the Intracoronary Stenting and Angiographic Restenosis-Test Equivalence Between Two Drug-Eluting Stents (ISAR-TEST) randomized trial.. A total of 450 patients undergoing percutaneous coronary intervention were randomized to receive either PF-SES (Yukon, Translumina; n = 225) or PES (Taxus, Boston Scientific; n = 225). Clinical follow-up was performed to 5 years after enrollment. The endpoints were major adverse cardiac events (MACE), target lesion revascularization (TLR), the composite of death or any myocardial infarction (MI) and stent thrombosis (ST). The incidence of MACE at 5 years was 27.3% (57 patients) in the PF-SES group and 31.7% (65 patients) in the PES group [hazard ratio (HR) = 0.87 [95% confidence interval (95% CI) = 0.61-1.24]; P = 0.40]. The combined incidence of death or MI was 16.6% (34 patients) in the PF-SES group and 20.0% (39 patients) in the PES group (HR = 0.86 [95% CI = 0.54-1.36]; P = 0.52). The incidence of TLR was 16.5% (34 patients) in the PF-SES group and 16.4% (33 patients) in the PES group (HR = 1.03 [95% CI = 0.64-1.66]; P = 0.89). ST occurred in 0.5% (one patient) in the PF-SES group and 1.6% (three patients) in the PES group (HR = 0.33 [95% CI = 0.03-3.14]; P = 0.32).. Overall there was no significant difference in clinical outcomes between PF-SES and PES to 5 years. Extended follow-up supports the durability of efficacy and safety of PF-SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheterization; Confidence Intervals; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Polymers; Proportional Hazards Models; Prospective Studies; Prosthesis Failure; Risk Assessment; Sirolimus; Statistics, Nonparametric; Survival Rate; Time Factors; Treatment Outcome

To evaluate long-term patterns of luminal changes after implantation of different types of drug-eluting stents (DES), we analyzed the serial angiographic outcomes of patients implanted with zotarolimus-eluting stents (ZES), sirolimus-eluting stents (SES), or paclitaxel-eluting stents (PES).. Little is known regarding long-term luminal changes after DES implantation.. As a subgroup analysis of the ZEST trial, we performed complete angiographic evaluation immediately after the procedure and at 9 months and 2 years in 111 patients with 165 lesions (36 patients with ZES, 40 with SES, and 35 with PES).. Baseline clinical, angiographic, and procedural characteristics were similar among the three groups. Quantitative angiographic analysis revealed significant decreases in minimal luminal diameter 9 months after stent implantation in the ZES (from 2.71 ± 0.49 to 2.21 ± 0.42 mm, P < 0.001), SES (from 2.79 ± 0.49 to 2.58 ± 0.57 mm, P < 0.001), and PES (from 2.66 ± 0.45 to 2.19 ± 0.52 mm, P < 0.001) groups. However, significant late improvements with different degree in luminal diameter were observed between 9 months and 2 years in the ZES (from 2.21 ± 0.42 to 2.39 ± 0.58 mm, P = 0.001), SES (from 2.58 ± 0.57 to 2.66 ± 0.60 mm, P = 0.039), and PES (from 2.19 ± 0.52 to 2.43 ± 0.52 mm, P < 0.001) groups.. Serial angiographic follow-up study revealed a biphasic luminal response after DES implantation, characterized by an early progression phase for the first 9 months and a late regression phase from 9 months to 2 years.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Linear Models; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Republic of Korea; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

Polymer-free sirolimus- and probucol-eluting stents (Real Dual drug-eluting stents [DES]) is as effective as first-generation DES in treating coronary artery stenosis. It is unknown whether sirolimus-eluting stents containing biodegradable polymer (Excel) would be superior to real Dual DES. This study aimed to investigate the difference in target vessel revascularization (TVR) at 12 months in patients with coronary artery disease treated by the implantation of Dual DES or Excel stents.. Three hundred and forty-six patients with de novo coronary artery disease were recruited from six centers in China and randomly assigned to either the Dual DES or the Excel group. The primary endpoint was the occurrence of TVR at 12 months. The secondary endpoint was angiographic in-stent restenosis and late lumen loss at 13 months. Stent thrombosis (ST) served as the safety endpoint. Dual anti-platelet therapy (DAPT) was prescribed for 6 months.. Clinical follow-up for 12 months and repeat angiography at 13 months were available in 100% and >90% of patients, respectively. The ISR and in-stent late loss were significantly different between the Excel (3.1%, 0.09 ± 0.11 mm) and the Dual DES (19.5%, 0.36 ± 0.32 mm, P < 0.001, P < 0.001, respectively) groups. The TVR (3.5%) in the Excel group was significantly less than in the Dual DES group (13.9%, P = 0.001). The ST rate beyond 12 months in the Dual DES group was 0%, and this was 1.2% in the Excel group (P = 0.499).. The Excel stent was statistically superior to the Dual DES in terms of restenosis, late loss, and TVR for long lesions.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Chi-Square Distribution; China; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Disease-Free Survival; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Probucol; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

There have been no optical coherence tomographic (OCT) data directly comparing the pattern of strut coverage between the 2 second-generation drug-eluting stents in the early period. The aim of this prospective study was to evaluate early strut coverage using optical coherence tomography 3 months after Resolute zotarolimus-eluting stent (ZES-R) or everolimus-eluting stent (EES) implantation in de novo coronary artery lesions. A total of 40 patients who were suitable for the OCT procedure and consented to the study protocol were randomized 1:1 to receive either ZES-R or EES. Among these patients, 35 stented lesions (18 ZES-R, 17 EES) in 34 patients were evaluated by optical coherence tomography immediately and 3 months after stent implantation. Neointimal hyperplasia thickness, percentage of uncovered struts, and the proportion of malapposed struts were measured at 1-mm intervals. An uncovered strut was defined as having a neointimal hyperplasia thickness of 0 μm. At the 3-month OCT evaluation, mean neointimal hyperplasia thickness (ZES-R vs EES 74 ± 41 vs 75 ± 35 μm, p = 0.89) and mean percentage of uncovered struts (ZES-R vs EES 6.2 ± 6.9 vs 4.7 ± 5.1%, p = 0.62) were not significantly different between the groups. The percentage of malapposed struts was also similar between the groups (0.7 ± 2.2% for ZES-R and 0.7 ± 1.7% for EES, p = 0.64). Thrombi were documented in 3 stents (1 [5.6%] in a ZES-R vs 2 [11.8%] in EES, p = 0.60). In conclusion, early stent strut coverage on the basis of serial OCT evaluation was comparable between ZES-R and EES 3 months after stent implantation.

Topics: Aged; Antineoplastic Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Out-stent plaque characteristics and eosinophilic inflammatory response, which correlates with positive remodeling after first-generation drug-eluting stent implantation, may be associated with late restenosis and very late stent thrombosis. The differences of out-stent plaque characteristics were compared between paclitaxel-eluting stents (PES) and zotarolimus-eluting stents (ZES), using integrated backscatter-intravascular ultrasound (IB-IVUS).. Of 78 patients enrolled, 25 receiving PES and 25 receiving ZES had adequate IVUS assessment. Volumetric IVUS analysis was performed after stenting and at 8-month follow-up. Out-stent plaque change in the stented segment was compared on IB-IVUS. The relationship between systemic inflammatory response and out-stent plaque change was evaluated. In PES, vessel volume significantly increased (365-389 mm(3), P<0.0001), whereas it did not change in ZES (315-314 mm(3), P=0.81). In culprit lesions at baseline in PES, fibrous plaque tended to increase (3.1-3.6mm(2), P=0.051) and lipid plaque significantly increased (4.3-5.1mm(2), P=0.02), whereas in ZES the fibrous plaque significantly increased (2.9-4.0mm(2), P<0.0001) but lipid plaque significantly decreased (5.1-3.6mm(2), P<0.0001). Systemic eosinophil increase was significantly correlated with positive remodeling and out-stent lipid plaque increase.. Chronic out-stent plaque change in ZES consisted of less positive remodeling and more favorable effects on out-stent plaque characteristics than PES. Systemic eosinophil change might be a marker of out-stent lipid plaque change.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Eosinophils; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paclitaxel; Risk Factors; Sirolimus; Treatment Outcome; Tubulin Modulators; Ultrasonography, Interventional; Vasculitis; Ventricular Remodeling

The best way to manage restenosis in patients who have previously received a drug-eluting stent is unknown. We investigated the efficacy of paclitaxel-eluting balloons (PEB), paclitaxel-eluting stents (PES), and balloon angioplasty in these patients.. In this randomised, open-label trial, we enrolled patients older than 18 years with restenosis of at least 50% after implantation of any limus-eluting stent at three centres in Germany between Aug 3, 2009, and Oct 27, 2011. Patients were randomly assigned (1:1:1; stratified according to centre) to receive PEB, PES, or balloon angioplasty alone by means of sealed, opaque envelopes containing a computer-generated sequence. Patients and investigators were not masked to treatment allocation, but events and angiograms were assessed by individuals who were masked. The primary endpoint was diameter stenosis at follow-up angiography at 6-8 months. Primary analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00987324.. We enrolled 402 patients, of whom 137 (34%) were assigned to PEB, 131 (33%) to PES, and 134 (33%) to balloon angioplasty. Follow-up angiography at 6-8 months was available for 338 (84%) patients. PEB was non-inferior to PES in terms of diameter stenosis (38·0% [SD 21·5] vs 37·4% [21·8]; difference 0·6%, one-sided 95% CI 4·9%; p(non-inferiority)=0·007; non-inferiority margin of 7%). Findings were consistent in per-protocol analysis (p(non-inferiority)=0·011). PEB and PES were superior to balloon angioplasty alone (54·1% [25·0]; p(superiority)<0·0001 for both comparisons). Frequency of death, myocardial infarction, or target lesion thrombosis did not differ between groups.. By obviating the need for additional stent implantation, PEB could be a useful treatment for patients with restenosis after implantation of a drug-eluting stent.. Deutsches Herzzentrum.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Germany; Humans; Male; Middle Aged; Paclitaxel; Prospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Survival Analysis; Treatment Outcome

Evidence regarding therapy with drug-eluting stents in the left main coronary artery (LM) is based mostly on trials performed with first-generation drug-eluting stents. The aim of this study was to evaluate long-term clinical outcomes after treatment for unprotected LM disease with paclitaxel-eluting stents (PES) and everolimus-eluting stents (EES). The ESTROFA-LM is a multicenter retrospective registry including consecutive patients with unprotected LM disease treated with PES or EES. A total of 770 patients have been included at 21 centers, 415 with treated PES and 355 with EES. Treatment with 2 stents was more frequent with PES (17% vs 10.4%, p = 0.007), whereas intravascular ultrasound was more frequently used with EES (35.2% vs 26%, p = 0.006). The 3-year death and infarction survival rates were 86.1% for PES and 87.3% for EES (p = 0.50) and for death, infarction, and target lesion revascularization were 83.6% versus 82% (p = 0.60), respectively. Definite or probable thrombosis was 1.6% for PES and 1.4% for EES (p = 0.80). The use of 2 stents, age, diabetes, and acute coronary syndromes were independent predictors of mortality. In the subgroup of distal lesions, the use of intravascular ultrasound was an independent predictor of better outcome. Comparison of propensity score-matched groups did not yield differences between the 2 stents. In conclusion, the results of this multicenter registry show comparable safety and efficacy at 3 years for PES and EES in the treatment of LM disease. The use of bifurcation stenting techniques in distal lesions was a relevant independent predictor for events. The use of intravascular ultrasound appears to have a positive impact on patients treated for LM distal disease.

Topics: Aged; Antineoplastic Agents, Phytogenic; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Paclitaxel; Registries; Retrospective Studies; Sirolimus; Spain; Time Factors; Treatment Outcome

The purpose of this pre-specified analysis of the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY) was to assess device-specific outcomes relative to different duration of dual antiplatelet therapy (DAPT) after Everolimus- (EES), Paclitaxel (PES), Zotarolimus- (ZES-S) eluting, or bare metal stents (BMS).. We randomized 2013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group underwent up to 6 or 24 months clopidogrel therapy. The primary endpoint, which was a composite of death, myocardial infarction, or cerebrovascular accident, did not differ in patients receiving BMS [HR: 0.89 (95% CI: 0.54-1.45)], PES [HR: 0.74 (95% CI: 0.43-1.25)], or EES [HR: 0.63 (95% CI: 0.33-1.21)] implantation across DAPT groups, whereas it was significantly higher in ZES-S patients undergoing long when compared with short-term DAPT therapy (HR: 2.85, P = 0.0018), with positive interaction testing (P-value = 0.004). At the 6-month landmark analysis, heterogeneity across stent types persisted for the primary study endpoint and other secondary clinical outcomes, whereas patients receiving PES showed a significantly higher rate of definite, probable and definite, probable, possible stent thrombosis in the short DAPT regimen. No association in absolute or relative terms was noted between stent potency in inhibiting intimal hyperplasia and greater vulnerability to shorter DAPT therapy.. Our study suggests that optimal duration of DAPT may be stent-specific and it does not support a clear association between stent potency and vulnerability to shorter DAPT therapy. Trial Registration clinicaltrials.gov Identifier: NCT00611286. http://clinicaltrials.gov/ct2/show/NCT00611286?term=prodigy&rank=2.

Topics: Aged; Clopidogrel; Coronary Restenosis; Coronary Vessels; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Graft Occlusion, Vascular; Humans; Hyperplasia; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Sirolimus; Stents; Stroke; Ticlopidine; Tunica Intima

The present study was designed to examine the five-year angiographic follow-up of MACE-free patients enrolled in the PRISON II study.. In the PRISON II study a total of 200 patients were randomised to either bare metal stents (BMS) or sirolimus-eluting stents (SES) after successful recanalisation of total coronary occlusions (TCO). Patients free of MACE with available angiography at six months were approached for repeated angiography at five years. The primary endpoint was in-stent very late luminal loss (VLLL) at five years. The secondary endpoint was additional late luminal loss (ALLL) between six months and five years. At five years, repeated angiography was performed in 72 patients, 50/82 (61%) in the SES group and 22/58 (38%) in the BMS group. In-stent VLLL was lower in the SES group (0.19 mm ± 0.72 vs. 0.51 mm ± 0.71, p=0.09) compared to the BMS group and in-segment VLLL was comparable in both groups (0.01 mm±0.58 vs. 0.03 mm ± 0.73, p=0.89). Late catch-up in lumen diameter was observed in the SES group with a trend towards increased ALLL compared to the BMS group (in-stent, 0.35 mm ± 0.88 vs. 0.04 mm ± 0.81, p=0.16; in-segment, 0.20 mm ± 0.74 vs. -0.05 mm ± 0.73, p=0.19).. At five-year angiographic follow-up, late catch-up was observed after successful recanalisation of TCOs treated with SES. Despite a late catch-up, the angiographic results of SES were superior in-stent and similar in-segment compared to BMS.

Topics: Adult; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Metals; Middle Aged; Netherlands; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome

The Nobori stent is a new drug-eluting stent (DES) with biodegradable polymer coating limited to the abluminal side of stents. Biolimus A9 is a novel sirolimus derivative specifically developed for DES, and polymer load 15.6 μg of biolimus A9 per 1 mm of stent. A non-randomized multicenter trial was conducted in Japan. Twenty-two de novo lesions were treated by Nobori stents and biolimus A9 concentration in whole blood was serially measured at 14 predetermined time points using a validated chromatography-tandem mass spectrometry (LC-MS/MS) assay. The C max was 85.3 ± 37.9 pg/mL (min-max 46.7-169 pg/mL) in the 18 mm cohort and 198 ± 81 pg/mL (min-max 82.5-365 pg/mL) in the ≥ 28 mm cohort and no early or late bursts of biolimus A9 release were documented. After 4 weeks, no measurable concentration of biolimus A9 was observed in any patient. Estimated AUC0-t was 1.12 ± 1.16 ng/mL h in the 18 mm group, and 5.93 ± 4.41 ng/mL h for the ≥ 28 mm group. A significant association between loaded biolimus A9 dose adjusted by patient weight and pharmacokinetic parameters was observed. The systemic exposure of biolimus A9 eluting from the Nobori stent was low and proportional to the loaded amount of biolimus A9, and clearance from the blood was rapid. These findings suggest that the Nobori stent is feasible and safe. Systemic lower exposure of biolimus A9 after Nobori stent implantation may have beneficial effects on stent endothelialization.

Topics: Aged; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Area Under Curve; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Prospective Studies; Prosthesis Design; Risk Assessment; Sirolimus; Time Factors; Treatment Outcome

The aim of this randomized-controlled trial is to compare biolimus A9-eluting stent (Nobori) to sirolimus eluting stent (Cypher).. The Nobori coronary stent is coated only abluminally with a biodegradable polymer, poly-lactic acid, and the antiproliferative agent biolimus A9. This stent has been studied in randomized trials versus Taxus Express and Taxus Liberte and showed noninferiority and superiority for in-stent late loss. This is the first randomized trial of Nobori stent versus Cypher stent.. We conducted a randomized (3:2), controlled trial comparing Nobori and Cypher, in 335 patients (198 Nobori and 137 Cypher) at 15 centers in Japan. Patients with de-novo lesions in up to two native coronary arteries were considered for enrollment. The primary endpoint was freedom from target vessel failure (TVF), a composite of cardiac death, myocardial infarction, and target vessel revascularization at 9 months.. At 9 months, the primary endpoint of freedom from TVF was 92.6% in Nobori and 93.8% in Cypher arm (noninferiority test P < 0.001). As main secondary endpoints, the in-stent late loss was 0.12 ± 0.30 mm and 0.14 ± 0.34 mm in Nobori and Cypher stents, respectively. Target lesion revascularization was 0.5% in Nobori and 3.9% in Cypher treated patients (P = 0.04). Definite and probable stent thromboses were not recorded in any patient.. Despite the relatively small number of patients, this well controlled clinical trial confirmed the primary hypothesis of non-inferiority of the Nobori biolimus A9-eluting stent to the Cypher sirolimus-eluting stent for freedom from TVF. Both stents showed excellent midterm results.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Japan; Lactic Acid; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polyesters; Polymers; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

The aim of this study was to examine the five-year clinical outcome in patients enrolled in the Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II) study.. Patients with totally occluded coronary arteries were randomised to either sirolimus-eluting stent (SES, n=100) or bare metal stent (BMS, n=100) implantation. At five years, patients in the SES group had significantly lower rates of target lesion revascularisation (12% vs. 30%, p=0.001), target vessel revascularisation (17% vs. 34%, p=0.009) and major adverse cardiac events (12% vs. 36%, p<0.001). There were no significant differences in death and myocardial infarction. Eight (8%) cases of stent thrombosis (seven definite and one probable; one early, one late, and six very late) were noticed in the SES group versus three cases (3%, one definite and two possible; all very late) in the BMS group (p=0.21).. The results of the present study show that the documented superior short-term angiographic and clinical results of SES in patients with total coronary occlusions are maintained during long-term 5-year follow-up as compared with BMS. On the other hand, there is a trend to a higher stent thrombosis rate in the SES group.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Metals; Middle Aged; Myocardial Infarction; Sirolimus; Stents; Survival Rate; Thrombosis; Treatment Outcome

The Oral Rapamycin in ARgentina (ORAR) III trial is a randomized study comparing a strategy of oral rapamycin (OR) plus bare-metal stent (BMS) versus a strategy of drug-eluting stents (DES) in patients with de novo coronary lesions. The purpose of this study was to assess the 3 years cost-effectiveness outcome of each strategy.. OR after BMS has been associated with reduction of target vessel revascularization (TVR) although its value in long-term efficacy in comparison with DES is unknown.. In three hospitals in Buenos Aires, Argentina, 200 patients were randomized to OR plus BMS (n = 100) or DES (n = 100). Primary objectives were costs and effectiveness. Cost analysis included in-hospital and follow-up costs. Safety was defined as the composite of death, myocardial infarction (MI), and stroke. Efficacy was defined as TVR.. Baseline characteristics between groups were similar. The 3-year follow-up rate was 99%. Cardiac mortality was 2% and 5% in OR group and DES group, respectively (P = 0.44). The composite of death, MI and stroke rate was 11% in OR group and 20% in DES group (P = 0.078). TVR rate was 14.5% in OR group and 17.6% in DES group (P = 0.50), respectively. Three year cumulative costs were significantly lower in the OR arm as compared to the DES arm (P = 0.0001) and DES strategy did not result cost-effective according to the non-inferiority test.. At 3 years follow-up, there were no differences in effectiveness between the two strategies, and DES strategy was not more cost-effective as compared to OR plus BMS.

Topics: Administration, Oral; Aged; Argentina; Cardiovascular Agents; Chi-Square Distribution; Combined Modality Therapy; Coronary Artery Disease; Coronary Restenosis; Cost Savings; Cost-Benefit Analysis; Drug Costs; Drug-Eluting Stents; Female; Health Care Costs; Hospital Costs; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Multivariate Analysis; Myocardial Infarction; Percutaneous Coronary Intervention; Proportional Hazards Models; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Stents; Stroke; Time Factors; Treatment Outcome

The SPIRIT Small Vessel (SV) was designed to evaluate the safety and effectiveness of the 2.25-mm XIENCE V everolimus eluting coronary stent system (EECSS), known as the XIENCE nano EECSS, in subjects with SVs and ischemic heart disease.. The core sizes of XIENCE V EECSS are associated with low rates of restenosis and thrombosis in the general population, but the XIENCE nano EECSS has not been tested in the United States.. This prospective, single-arm, open-label study was conducted at 33 centers and in 150 patients in the United States. The primary endpoint was the target lesion failure (TLF) rate at 1 year, required to meet the prespecified performance goal (PG) of 20.4%, derived from historical data.. The mean patient age was 63 years, 38% were women, 39.2% were diabetic, 49.3% had multivessel disease, and the reference vessel diameter was 2.13 ± 0.23 mm. The 1-year TLF rate was 8.1% in with an upper limit of the one-sided 95% confidence interval of 13.0%, which met the PG of 20.4% (P < 0.0001). At 1 year, the rate of cardiac death was 1.5%, the target vessel myocardial infarction rate was 1.5%, and clinically indicated target lesion revascularization rate was 5.1%. The 8-month angiographic in-stent late loss was 0.2 ± 0.4 mm, respectively. The 1-year academic research consortium defined definite/probable stent thrombosis rate was 1.5%.. Based on the 1-year clinical and 8-month angiographic SPIRIT SV data, the XIENCE nano EECSS is considered safe and effective in the treatment of SVs.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Nanomedicine; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; United States

Even in the drug-eluting stent era, adverse cardiac events, including restenosis after percutaneous coronary intervention (PCI), have been more frequently seen in patients on hemodialysis (HD) than in non-HD patients. The objective of this study was to compare the sirolimus-eluting stent (SES) and everolimus-eluting stent (EES) for prevention of adverse cardiac events, including restenosis, in HD patients.. A total of 100 consecutive patients on HD who underwent PCI were enrolled and randomly assigned to receive SES or EES. Although there was no difference between the 2 groups in baseline patient and lesion characteristics, the angiographic restenosis rate at 8-month follow-up was 21.2% in the SES group and 8.7% in the EES group (P = 0.041). Significant differences were also seen in % diameter stenosis (%DS), minimal lumen diameter, and late lumen loss at 8-month follow-up (P = 0.0024, P = 0.0040, and P = 0.033, respectively). During the 1-year follow-up, major adverse cardiac events occurred in 11 (22.0%) patients in the SES group and in 5 (10.0%) patients in the EES group (P = 0.10).. The use of EES was as safe as that of SES. Moreover, EES significantly prevented restenosis in patients on maintenance HD compared with SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Sirolimus; Treatment Outcome

Limited data are available regarding the direct comparison of angiographic and clinical outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) for chronic total occlusion (CTO).. A prospective, randomized, multicenter trial was conducted to evaluate the non-inferiority of a zotarolimus-eluting stent (ZES; Endeavor Sprint®, n=80) to a sirolimus-eluting stent (SES; Cypher®, n=80) in patients with CTO lesion with a reference vessel diameter ≥ 2.5mm. The primary endpoint was in-segment binary restenosis rate at 9-month angiographic follow-up. Key secondary endpoints included target vessel failure (TVF; including cardiac death, myocardial infarction, and target vessel revascularization) and Academic Research Consortium-defined definite/probable stent thrombosis (ST) within 12 months. The ZES was non-inferior to the SES with respect to the primary endpoint, which occurred in 14.1% (95% confidence interval [CI]: 6.0-22.2) and in 13.7% (95%CI: 5.8-21.6) of patients, respectively (non-inferiority margin, 15.0%; P for non-inferiority <0.001). There were no significant between-group differences in the rate of TVF (10.0% vs. 17.5%; P=0.168) nor in the rate of ST (0.0% vs. 1.3%; P=0.316) during the 12-month clinical follow-up.. The effectiveness and safety of ZES are similar to those of SES and therefore it is a good treatment option in patients undergoing PCI for CTO with DESs.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Prosthesis Design; Republic of Korea; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Among drug-eluting stents released to date, the sirolimus-eluting stent has demonstrated the least amount of late lumen loss, but its efficacy and safety have not been compared head-to-head with the next-generation everolimus-eluting stent.. The Scandinavian Organization for Randomized Trials with Clinical Outcome IV (SORT OUT IV) trial was a randomized multicenter, single-blind, all-comer, 2-arm, noninferiority trial comparing the everolimus-eluting stent with the sirolimus-eluting stent in patients with coronary artery disease. The primary end point was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularization) parameters. The noninferiority criterion was a risk difference of 0.015. Intention-to-treat analyses were done at 9- and 18-month follow-ups. A total of 1390 patients were assigned to receive the everolimus-eluting stent and 1384 patients to the sirolimus-eluting stent. At the 9-month follow-up, 68 patients (4.9%) treated with the everolimus-eluting stent compared with 72 patients (5.2%) treated with the sirolimus-eluting stent experienced the primary end point (hazard ratio, 0.94; 95% confidence interval, 0.67-1.31; P for noninferiority=0.01). At the 18-month follow-up, this differential remained: 99 patients (7.2%) treated with the everolimus-eluting stent versus 105 (7.6%) treated with the sirolimus-eluting stent (hazard ratio, 0.94; 95% confidence interval, 0.71-1.23). At the 9-month follow-up, the rate of definite stent thrombosis was higher in the sirolimus-eluting group (2 patients [0.1%] versus 9 patients [0.7%]; hazard ratio, 0.22; 95% confidence interval, 0.05-1.02). At the 18-month follow-up, this difference was sustained (3 patients [0.2%] versus 12 patients [0.9%]; hazard ratio, 0.25; 95% confidence interval, 0.07-0.88).. The everolimus-eluting stent was found to be noninferior to the sirolimus-eluting stent.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00552877.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Risk Factors; Sirolimus; Treatment Outcome

Data from randomized clinical trials have shown the safety and efficacy of the XIENCE V in selected populations. However, limited data are available comparing the XIENCE V to the first-generation CYPHER sirolimus-eluting stent. This study aimed to assess the long-term safety and clinical efficacy of the XIENCE V everolimus-eluting stent compared to first-generation stents in an unselected patient population. This retrospective analysis included 6,069 patients treated with CYPHER, TAXUS, and XIENCE stents from 2003 to 2009 at our institution. The patients were followed up for ≥1 year after the index procedure. The baseline characteristics were generally comparable among the 3 groups, with the exception of a significantly greater prevalence of diabetes mellitus, systemic hypertension, and a history of angioplasty and coronary bypass surgery among the XIENCE patients. The XIENCE patients also had a twofold greater rate of type C lesions. One-year follow-up data were available for 82% of the patients. The 1-year major adverse cardiovascular events rate was 9.3% for the XIENCE stent versus 9.8% for the CYPHER stent and 11.5% for the TAXUS stent (p = 0.11). Mortality was lower in the XIENCE group than in the CYPHER and TAXUS groups (3.6% vs 4.9% vs 7.2%, respectively, p <0.001), and target lesion revascularization was similar (5.9% vs 5.2% vs 5.6%, respectively; p = 0.34). Stent thrombosis was lower in the XIENCE patients (0.2% vs 1.2% vs 0.7%, p = 0.007). In conclusion, in a contemporary United States clinical practice with an unselected patient population, use of the XIENCE V stent was associated with an improved safety profile and reduction of all-cause mortality and stent thrombosis compared to first-generation drug-eluting stents. The XIENCE V failed to demonstrate superiority for overall major adverse cardiovascular events, Q-wave myocardial infarction, and revascularization rates.

Topics: Aged; Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Prosthesis Design; Retrospective Studies; Sirolimus; Treatment Outcome

Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions.. Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed.. In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

Topics: Aged; Anticholesteremic Agents; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Simvastatin; Sirolimus; Ultrasonography, Interventional

Therapeutic strategies preventing late target lesion revascularization (TLR) after drug-eluting stent implantation have not been yet adequately investigated. In 13,087 consecutive patients undergoing first percutaneous coronary intervention in the CREDO-Kyoto Registry Cohort-2, we identified 10,221 patients who were discharged alive after implantation of sirolimus-eluting stents (SESs) only (SES stratum 5,029) or bare-metal stents (BMSs) only (BMS stratum 5,192). Impact of statin therapy at time of discharge from the index hospitalization on early (within the first year) and late (1 year to 4 years) TLR, was assessed in the SES stratum (statin group 2,735; nonstatin group 2,294) and in the BMS stratum (statin group 2,576; nonstatin group 2,616). Despite a significantly lower incidence of early TLR (7.8% vs 22.2%, p <0.0001), SES use compared to BMS use was associated with a significantly higher incidence of late TLR (7.7% vs 3.0%, p <0.0001). In the SES and BMS strata, the incidence of early TLR was similar regardless of statin use. In the SES stratum, the incidence of late TLR was significantly lower in the statin group than in the nonstatin group (6.1% vs 9.6%, p = 0.002), whereas no significant difference was found in the BMS stratum (2.6% vs 3.3%, p = 0.38). After adjusting confounders, risk for late TLR significantly favored statin use in the SES stratum (hazard ratio 0.73, 95% confidence interval 0.54 to 0.98, p = 0.04), whereas the risk decrease was not significant in the BMS stratum (hazard ratio 0.74, 95% confidence interval 0.46 to 1.20, p = 0.23). In conclusion, statin therapy at hospital discharge was associated with a significantly lower risk for late TLR after SES implantation.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Incidence; Male; Myocardial Infarction; Myocardial Revascularization; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

The purpose of this study is to compare the efficacy of the treatment strategies for in-stent restenosis (ISR) of drug-eluting stents (DES) according to the morphologic pattern of restenosis.. Optimal treatment strategies for ISR within DES have not been adequately addressed yet.. Patients with ISR of DES were randomized according to the lesion length to compare outcomes of sirolimus-eluting stent (SES) versus cutting balloon angioplasty for focal type (≤10 mm) and SES versus everolimus-eluting stent (EES) for diffuse type (>10 mm). The primary endpoint was in-segment late loss at 9 months. Overall 162 patients, 96 with focal ISR and 66 with diffuse ISR, were enrolled.. In focal lesions, in-segment late loss was significantly higher in the cutting balloon group (n = 48) than in the SES group (n = 48; 0.25 mm, interquartile range [IQR]: -0.01 to 0.68 mm vs. 0.06 mm, IQR: -0.08 to 0.17 mm; p = 0.04). Consequently, in-segment restenosis rate tended to be higher in the cutting balloon group than in the SES group (20.7% vs. 3.1%, p = 0.06) with comparable incidences of the composite of death, myocardial infarction, or target vessel revascularization at 12 months of clinical follow up (6.3% vs. 6.3%, p > 0.99). In 66 cases of diffuse ISR, in-segment late loss (0.11 mm, IQR: -0.02 to 0.30 mm; vs. 0.00 mm, IQR: -0.08 to 0.25 mm; p = 0.64), in-segment restenosis rate (5.0% vs. 14.3%, p = 0.32), and the composite incidence of death, myocardial infarction, or target lesion revascularization (9.6% vs. 8.8%, p > 0.99) did not differ between SES group (n = 32) and EES group (n = 34).. For lesions of focal DES restenosis, repeat implantation of SES is more effective in reducing late luminal loss and subsequent restenosis rate than cutting balloon angioplasty. For diffuse DES restenosis, implantation of SES or EES is comparably effective in terms of angiographic and clinical outcomes.

Topics: Aged; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Confounding Factors, Epidemiologic; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Electrocardiography; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Reoperation; Republic of Korea; Sirolimus; Treatment Outcome

The aim of this study was to evaluate the 5-year clinical safety and efficacy outcomes of patients treated for in-stent restenosis of bare-metal stents (BMSs).. The SISR trial is a prospective, randomized trial that compared the safety and efficacy of sirolimus-eluting stent (SES) vs vascular brachytherapy (VBT) for the treatment of BMS in-stent restenosis.. A total of 384 patients with BMS in-stent restenosis were randomized to treatment with SES (n = 259) or VBT (n = 125) and were followed for 5 years.. At 5 years, the rates of target lesion revascularization (TLR) had narrowed and were nonsignificant between the SES and VBT groups, with TLR rates of 24.7% and 31.2% (95% CI -16.3% to 2.8%, P = .179) respectively. Target vessel failure was 33.6% vs 36.8% (95% CI -13.5% to 6.7% P = .568) for SES compared with VBT. The rate of major adverse cardiac event at 5 years was 34.0% vs 36.8% (95% CI -13.1% to7.1%, P = .648) for the SES compared with VBT. There were no differences between SES and VBT in terms of survival free from TLR (72.9% vs 66.4%, log-rank P = .08) or from target vessel failure (64.4% vs 61.3%, log-rank P = .349). There were no significant differences in the rates of definite/probable stent thrombosis (5.9% vs 2.5%, 95% CI -7.9% to 1.3%, P = .182) between the 2 groups.. At a 5-year follow-up, no differences in safety or efficacy outcomes were observed for treatment of BMS restenosis with SES vs VBT. There were no significant differences in survival free from TLR, target vessel revascularization, or major adverse cardiac events between the 2 groups at 5 years. Sirolimus-eluting stent is a viable treatment option compared with VBT for BMS restenosis.

Topics: Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease-Free Survival; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Sirolimus; Time Factors; Treatment Outcome

The optimal duration of dual-antiplatelet therapy and the risk-benefit ratio for long-term dual-antiplatelet therapy after coronary stenting remain poorly defined. We evaluated the impact of up to 6 versus 24 months of dual-antiplatelet therapy in a broad all-comers patient population receiving a balanced proportion of Food and Drug Administration-approved drug-eluting or bare-metal stents.. We randomly assigned 2013 patients to receive bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting stent implantation. At 30 days, patients in each stent group were randomly allocated to receive up to 6 or 24 months of clopidogrel therapy in addition to aspirin. The primary end point was a composite of death of any cause, myocardial infarction, or cerebrovascular accident. The cumulative risk of the primary outcome at 2 years was 10.1% with 24-month dual-antiplatelet therapy compared with 10.0% with 6-month dual-antiplatelet therapy (hazard ratio, 0.98; 95% confidence interval, 0.74-1.29; P=0.91). The individual risks of death, myocardial infarction, cerebrovascular accident, or stent thrombosis did not differ between the study groups; however, there was a consistently greater risk of hemorrhage in the 24-month clopidogrel group according to all prespecified bleeding definitions, including the recently proposed Bleeding Academic Research Consortium classification.. A regimen of 24 months of clopidogrel therapy in patients who had received a balanced mixture of drug-eluting or bare-metal stents was not significantly more effective than a 6-month clopidogrel regimen in reducing the composite of death due to any cause, myocardial infarction, or cerebrovascular accident.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00611286.

Topics: Aged; Aged, 80 and over; Aspirin; Cause of Death; Clopidogrel; Coronary Restenosis; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Platelet Aggregation Inhibitors; Risk; Sirolimus; Stroke; Thrombosis; Ticlopidine; Treatment Outcome

Early generation drug-eluting stents (DESs) reduce restenosis and repeat revascularization procedures. However, the long-term safety and efficacy of early generation DES according to diabetic status are poorly established.. A total of 1,012 patients were randomly assigned to treatment with sirolimus-eluting (n = 503) or paclitaxel-eluting stents (n = 509). Serial angiographic follow-up at baseline, 8 months, and 5 years was available in 293 patients with 382 lesions. The primary end point was a composite of major adverse cardiac events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization). Clinical and angiographic outcomes through 5-year follow-up were compared between diabetic and nondiabetic patients.. Major adverse cardiac events were more common among diabetic than nondiabetic patients at 5 years (25.9% vs 19.2%, hazard ratio [HR] 1.45, 95% CI 1.06-1.99, P = .02). The difference in disfavor of diabetic patients was largely determined by a higher rate of cardiac mortality (11.4% vs 4.3%, HR 2.86, 95% CI 1.69-4.84, P < .0001), whereas the risk of myocardial infarction (6.5% vs 6.8%, HR 1.00, 95% CI 0.55-1.84, P = .99) and ischemia-driven target lesion revascularization (14.4% vs 14.1%, HR 1.09, 95% CI 0.73-1.64, P = .67) was comparable. The risk of stent thrombosis was similar among diabetic and nondiabetic patients (definite or probable: 6.0% vs 4.6%, HR 1.36, 95% CI 0.71-2.67, P = .35). Among 293 patients undergoing serial angiography, very-late lumen loss amounted to 0.42 ± 0.63 mm in diabetic patients and 0.44 ± 0.68 mm in nondiabetic patients (P = .79).. Diabetic patients remain at increased risk for mortality after revascularization with early generation DES during long-term follow-up. Conversely, diabetes is no longer associated with an increased risk of clinical and angiographic restenosis after revascularization with early generation DES.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Proportional Hazards Models; Prosthesis Design; Reference Values; Risk Assessment; Severity of Illness Index; Sirolimus; Survival Analysis; Time; Time Factors; Treatment Outcome

To compare clinical outcomes among patients with acute coronary syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the SORT OUT III trial.. Currently, only limited data allow direct comparison of clinical outcomes among patients with acute coronary syndrome treated with a second-generation drug-eluting stent (DES) eluting zotarolimus vs. a first-generation DES eluting sirolimus.. Patients with acute coronary syndrome (n=1052) were randomized to treatment with zotarolimus-eluting (n=506) or sirolimus-eluting (n=546) stents and followed for 18 months. The primary composite endpoint, major adverse cardiac events (MACE), was defined as a composite of cardiac death, myocardial infarction or target vessel revascularization.. Zotarolimus-eluting stent treatment compared to sirolimus-eluting stent treatment was associated with increased rates of MACE (8·7% vs. 5·0%; hazard ratio (HR), 1·78; 95% confidence interval (CI), 1·10-2·88; P=0·02) and TVR (6·8% vs. 3·9%; HR, 1·77; 95% CI, 1·03-3·04; P=0·04), while all-cause death, cardiac death, myocardial infarction and definite stent thrombosis did not differ significantly. In the same trial, stable angina pectoris patients (n=1206) were randomized to zotarolimus-eluting (n=614) and sirolimus-eluting (n=592) stents with similar results.. With and without acute coronary syndromes, patients treated with the sirolimus-eluting stent had better clinical outcomes than those treated with the zotarolimus-eluting stent.

Topics: Acute Coronary Syndrome; Angina, Stable; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Sirolimus; Treatment Outcome

This study sought to evaluate the safety and efficacy of second-generation drug-eluting stents (DES) for patients with unprotected left main coronary artery (ULMCA) stenosis.. The clinical benefit of second-generation DES for ULMCA stenosis has not been determined.. The authors assessed 334 consecutive patients who received everolimus-eluting stents (EES) for ULMCA stenosis between 2009 and 2010. The 18-month incidence rates of major adverse cardiac or cerebrovascular events (MACCE), including death, myocardial infarction (MI), stroke, or ischemia-driven target vessel revascularization (TVR), were compared with those of a randomized study comparing patients who received sirolimus-eluting stents (SES) (n = 327) or coronary artery bypass grafts (CABG) (n = 272).. EES (8.9%) showed a comparable incidence of MACCE as SES (10.8%; adjusted hazard ratio [aHR] of EES: 0.84; 95% confidence interval [CI]: 0.51 to 1.40; p = 0.51) and CABG (6.7%, aHR of EES: 1.40; 95% CI: 0.78 to 2.54; p = 0.26). The composite incidence of death, MI, or stroke also did not differ among patients receiving EES (3.3%), SES (3.7%; aHR of EES: 0.63; 95% CI: 0.27 to 1.47; p = 0.29), and CABG (4.8%; aHR of EES: 0.67; 95% CI: 0.29 to 1.54; p = 0.34). However, the incidence of ischemia-driven TVR in the EES group (6.5%) was higher than in the CABG group (2.6%, aHR of EES: 2.77; 95% CI: 1.17 to 6.58; p = 0.02), but comparable to SES (8.2%, aHR of EES: 1.14; 95% CI: 0.64 to 2.06; p = 0.65). Angiographic restenosis rates were similar in the SES and EES groups (13.8% vs. 9.2%, p = 0.16).. Second-generation EES had a similar 18-month risk of MACCE for ULMCA stenosis as first-generation SES or CABG.

Topics: Confidence Intervals; Coronary Artery Bypass; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Risk; Sirolimus

Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization.. Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES (P(noninferiority)<0.0001, and P(superiority)=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P=0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, P(noninferiority)<0.0001, and P(superiority)=0.24) at 278±63 days after index stent implantation.. One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Japan; Male; Middle Aged; Prospective Studies; Sirolimus; Treatment Outcome

The goal of this study was to compare the efficacy and safety of second-generation everolimus-eluting stents (EES) with first-generation sirolimus-eluting stents (SES) in primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).. Drug-eluting stents (DES) in AMI are still feared for possible late and very late stent thrombosis (ST). Newer-generation DES, with more hemocompatible polymers and improved healing, may show promise regarding increased efficacy of DES with improved safety. However, no randomized trials in AMI are available.. A total of 625 patients with AMI were randomized (2:1) to receive EES or SES in the XAMI (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction) trial. Primary endpoint was major adverse cardiac events (MACE) at 1 year consisting of cardiac death, nonfatal AMI, or any target vessel revascularization. The study was powered for noninferiority of EES. Secondary endpoints comprised ST rates and MACE rate up to 3 years.. The MACE rate was 4.0% for EES and 7.7% for SES; the absolute difference was -3.7% (95% confidence interval: -8.28 to -0.03; p = 0.048) and relative risk was 0.52 (95% confidence interval: 0.27 to 1.00). One-year cardiac mortality was low at 1.5% for EES versus 2.7% for SES (p = 0.36), and 1-year incidence of definite and/or probable ST was 1.2% for EES versus 2.7% for SES (p = 0.21).. In this all-comer, randomized, multicenter AMI trial, second-generation EES was noninferior to SES, and superiority for MACE was suggested. ST rate in EES at 1-year was low, but long-term follow-up and larger studies will have to show whether very late ST rates will also be improved in newer DES. (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction [XAMI]; NTR1123).

Topics: Aged; Angioplasty, Balloon, Coronary; Cause of Death; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Sirolimus; Survival Rate

Restenosis after PCI and/or stent implantation is still one of the challenging problems in the field of interventional cardiology. Different approaches to prevent and to treat restenosis include the use of drug-eluting stents, which have shown to reduce restenosis. Another approach is the treatment with drug-coated balloons. This approach has been proven for different indications, e.g., in-stent restenosis and treatment of peripheral artery disease.. Patients from the PEPCAD III multicentre randomised trial in two study centres (Homburg and Hannover, Germany) were asked to participate in this intravascular ultrasound (IVUS) study at nine-month follow-up. At baseline (nine months before), patients were randomly assigned to receive either a paclitaxel-coated balloon (drug-coated balloon [DCB]) plus a premounted bare metal stent (DCB/BMS) or a sirolimus-eluting stent (drug-eluting stent [DES]) to treat de novo lesions. IVUS at follow-up was performed in order to analyse the restenosis for potential understanding of the mechanism leading to restenosis. IVUS data is available for 55 patients; 26 patients were treated with Cypher(®) DES (Cordis, Miami Lakes, FL, USA) and 29 patients with DCB/BMS. A focal malapposition of the stent was seen in six patients; four after DES and two after DCB/BMS. Stent expansion, calculated as symmetric expansion index, was equal for both groups (0.89 and 0.90). Mean stent area was also equal for both groups (6.25 ± 1.7 vs. 5.65 ± 1.5 mm(2), p=n.s.). The neointimal hyperplasia (calculated as stent area minus lumen area) was significantly different between both groups (0.69 ± 0.49 [DES] vs. 1.08 ± 0.53 mm(2) [DCB/BMS], p<0.01). This resulted in a significantly higher in-stent restenosis in the DCB/BMS group (19.7 vs. 11 %, p<0.01). There is no evidence of geographical mismatch.. First IVUS insights for the DCB/BMS showed a comparable, low incidence of malapposition for the combination of drug-coated balloon and premounted bare metal stent compared to the DES, and stent expansion was good and comparable to DES. However, at nine-month follow-up, the combination of drug-coated balloon and premounted bare metal stent showed higher in-stent restenosis compared to sirolimus DES. Geographical mismatch can be excluded as a reason for this result.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Equipment Failure; Follow-Up Studies; Foreign-Body Migration; Humans; Incidence; Middle Aged; Neointima; Paclitaxel; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions.. Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957.. PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58-1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years.. No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis.. Medtronic, Inc.

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Sirolimus; Thrombosis

 We compared the efficacy of the Cypher Select (Cordis Corporation, Bridgewater, NJ, USA) sirolimus-eluting stent (SES) versus balloon angioplasty (BA) in in-stent restenosis (ISR) of Taxus or Taxus Liberté paclitaxel-eluting stents (PES; Boston Scientific, Natick, MA, USA) or Cypher/Cypher Select SES.. Optimal treatment strategies have not been identified for drug-eluting stent (DES) ISR.. Patients with a native coronary artery SES or PES ISR were randomized to SES or BA. In addition, a control group included BMS ISR treated with SES. Angiographic control was performed at 12 months.. 281 patients were enrolled. Significant differences favoring SES over BA were noted in immediate and net gain (1.39 ± 0.51 vs. 0.97 ± 0.54 mm, P < 0.0001 and 1.07 ± 0.69 vs. 0.49 ± 0.67 mm, P < 0.0001), 12-month mean luminal diameter (MLD; 2.14 ± 0.62 vs. 1.71 ± 0.55 mm, P < 0.0001) and percent diameter stenosis (%DS; 21 ± 19.24 vs. 29.82 ± 18.47, P = 0.001). There was no significant difference at 12 months between SES and BA in the primary end-point late lumen loss (LLL; 0.37 ± 0.57 vs.0.41 ± 0.63, P = 0.73) and in in-stent binary restenosis (11.1% vs. 14%, P = 0.59). Target-lesion revascularization (TLR) was numerically lower in patients treated with SES (5.9% vs. 13.1%, P = 0.097). There was no difference according to the initial DES. In contrast, significantly higher immediate and net gains and MLD were noted in the BMS control group treated by SES.. In this angiographic randomized trial comparing SES and BA in SES or PES restenosis, 12 month MLD, immediate and net gain, and %DS favored SES whereas no difference was noted in LLL. Condensed abstract optimal treatment strategies have not been identified for sirolimus-(SES) or paclitaxel-eluting stent (PES) in-stent restenosis (ISR). We randomized patients with a native coronary artery SES or PES ISR to SES or BA. In addition, a control group included BMS ISR treated with SES. There was no difference in the primary end-point, late lumen loss (LLL) at 12 months between the SES and BA groups. However, follow-up MLD and immediate and net gain favored SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Paclitaxel; Sirolimus

We retrospectively analyzed the midterm clinical and angiographic outcomes after the implantation of paclitaxel- (PES, TAXUS Express) and sirolimus- (SES, Cypher Bx Velocity) eluting stents in Japanese patients with complex coronary lesions.. From August 2004 to May 2009, 1,335 nonrandomized de novo native complex coronary lesions treated with either a PES (357 cases) or SES were included. The inclusion criteria for patients with complex lesions were those with diabetes, those undergoing hemodialysis, and those with a low ejection fraction, as well as subjects who had lesions with severe calcification, ostiums of the right coronary and left circumflex arteries, and who underwent the side-branch bifurcation 2-stent technique. The subjects were evaluated for consistent predictors of cardiac events, binary restenosis and target lesion vascularization of the SES. The composite primary endpoint percentage (900-day cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis) after PES placement was 0.6%, which was not significantly different from that after SES placement (0.12%; p=0.290). The incidence of the secondary endpoint (binary restenosis; stenosis >50% of the diameter at the secondary angiographic examination performed within 550 days after the procedure) after PES placement (15.0%) was also not significantly different than that after SES placement (13.3%; p=0.498). There was no relationship between PES placement and binary restenosis upon angiographic follow-up of 989 lesions (odds ratio of 1.14; 95% confidence interval, 0.73-1.77; p=0.57).. For de novo native complex coronary stenosis, the midterm safety and efficacy of PES placement was statistically equivalent to that of SES placement in a clinical setting in Japan.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

Procedural and clinical outcomes still remain unfavorable for patients with long coronary lesions who undergo stent-based coronary interventions. Therefore, we compared the relative efficacy and safety of resolute zotarolimus-eluting stents (R-ZES) and sirolimus-eluting stents (SES) for patients with de novo long coronary lesions.. This randomized, multicenter, prospective trial, called the Percutaneous Treatment of LONG Native Coronary Lesions With Drug-Eluting Stent-IV (LONG-DES IV) trial, compared long R-ZES and SES in 500 patients with long (≥25 mm) native coronary lesions. The primary end point of the trial was in-segment late luminal loss at 9-month angiographic follow-up. The baseline characteristics were not different between R-ZES and SES groups, including lesion lengths (32.4±13.5 mm versus 31.0±13.5 mm, P=0.27). At 9-month angiographic follow-up, the R-ZES was noninferior to the SES with respect to in-segment late luminal loss, the primary study end point (0.14±0.38 mm versus 0.12±0.43 mm, P for noninferiority=0.03, P for superiority=0.68). In addition, in-stent late luminal loss (0.26±0.36 mm versus 0.24±0.42 mm, P=0.78) and the rates of in-segment (5.2% versus 7.2%, P=0.44) and in-stent (4.0% versus 6.0%, P=0.41) binary restenosis were not significantly different between the 2 groups. There were no significant between-group differences in the rate of adverse clinical events (death, myocardial infarction, stent thrombosis, target-lesion revascularization, and composite outcomes).. For patients with de novo long coronary artery disease, R-ZES implantation showed noninferior angiographic outcomes as compared with SES implantation.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186094.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Prosthesis Design; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Nonserial observations have shown this bioresorbable scaffold to have no signs of area reduction at 6 months and recovery of vasomotion at 1 year. Serial observations at 6 months and 2 years have to confirm the absence of late restenosis or unfavorable imaging outcomes.. The ABSORB trial is a multicenter single-arm trial assessing the safety and performance of an everolimus-eluting bioresorbable vascular scaffold. Forty-five patients underwent serial invasive imaging, such as quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography at 6 and 24 months of follow-up. From 6 to 24 months, late luminal loss increased from 0.16±0.18 to 0.27±0.20 mm on quantitative coronary angiography, with an increase in neointima of 0.68±0.43 mm(2) on optical coherence tomography and 0.17±0.26 mm(2) on intravascular ultrasound. Struts still recognizable on optical coherence tomography at 2 years showed 99% of neointimal coverage with optical and ultrasonic signs of bioresorption accompanied by increase in mean scaffold area compared with baseline (0.54±1.09 mm(2) on intravascular ultrasound, P=0.003 and 0.77±1.33 m(2) on optical coherence tomography, P=0.016). Two-year major adverse cardiac event rate was 6.8% without any scaffold thrombosis.. This serial analysis of the second generation of the everolimus-eluting bioresorbable vascular scaffold confirmed, at medium term, the safety and efficacy of the new device.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856856.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Australia; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Diagnostic Imaging; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Male; Middle Aged; Neointima; New Zealand; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The purpose of this study was to investigate the vascular response of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) using serial intravascular ultrasound (IVUS).. Data were obtained from the SPIRIT III trial, a multicentre, 2:1 randomised, controlled study comparing EES and PES in de novo native coronary artery lesions. IVUS images were eligible for volumetric analysis at eight-month follow-up in 158 lesions (EES: 113, PES: 45). At eight months, EES had a smaller neointimal volume index (VI: mm3/mm) (EES: 0.4±0.4 vs. PES: 0.8±0.8 mm3/mm, p=0.002) and also a smaller % neointimal obstruction (EES: 7.1±6.7% vs. PES: 11.1±10.5%, p=0.005) compared with PES. While there was no significant change in vessel VI with EES, there was a significant increase in vessel VI in PES during eight-month follow-up (EES: 0.1±1.2 vs. PES: 1.2±0.8 mm3/mm, p=0.001). There were no statistical differences in the frequency of edge dissection or incomplete stent apposition between the two groups.. Detailed IVUS analysis confirmed significantly less neointimal hyperplasia with EES compared with PES. While there was no increase in vessel volume with EES during the eight-month follow-up period, vessel enlargement was seen at the stented segment in PES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Japan; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; United States

This study sought to evaluate the safety and efficacy of the NOYA stent which is a cobalt chromium-based sirolimus-eluting stent (SES) with DL-polylactide biodegradable polymer (Medfavour Medical, Beijing, China) in treating de novo coronary artery lesions.. The NOYA I trial was designed to compare the NOYA stent with the FIREBIRD2™ stent, a durable polymer SES widely used in China (MicroPort Medical, Shanghai, China); the trial was a non-inferiority trial with a primary angiographic endpoint of the in-stent late lumen loss (LLL) at nine-month follow-up. The secondary endpoints were binary restenosis rates within nine months, major adverse cardiac events (MACE) defined as the composite of cardiac death, myocardial infarction (MI) or target lesion revascularisation (TLR), and definite/probable stent thrombosis (ST) at 24-month follow-up. A total of 300 patients (n=150 in each group) were enrolled in the study from 16 Chinese centres. The LLL in the NOYA group at nine-month follow-up was similar to the FIREBIRD2 group (0.11±0.18 mm vs. 0.14±0.23 mm, p=0.16; non-inferiority p<0.001). The rates of MACE, death, MI and TLR at 24-month follow-up were comparable between these two devices (p>0.05, respectively).. The biodegradable polymer NOYA stent was non-inferior to the FIREBIRD2 durable polymer stent with respect to the primary non-inferiority endpoint of in-stent LLL at nine-month follow-up. Clinical outcomes at 24-month follow-up were comparable between the two stents. (ClinicalTrials.gov number, NCT01226355).

Topics: Absorbable Implants; Aged; Analysis of Variance; Cardiovascular Agents; Chi-Square Distribution; China; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polyesters; Predictive Value of Tests; Prosthesis Design; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO.. The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in the first 60 randomized patients at 9 months to assess neointima thickness, percentage of neointima coverage, and stent strut malapposition and coverage. Personnel blinded to the allocated treatment will review all angiographic and optical coherence assessments. Secondary clinical endpoints include major adverse cardiac events, clinically driven target vessel revascularization, target vessel failure and stent thrombosis to 5-year clinical follow-up. An independent clinical event committee blinded to the allocated treatment will review all clinical events.. Clinical Trials.gov: NCT01516723. Patient recruitment started in February 2012.

Topics: Angioplasty, Balloon, Coronary; Belgium; Cardiovascular Agents; Clinical Protocols; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Humans; Neointima; Netherlands; Polymers; Prospective Studies; Prosthesis Design; Research Design; Single-Blind Method; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The FOCUS registry is a prospective, multicentre, web-based programme designed to collect clinical outcome data from real-world patients receiving the second-generation cobalt-chromium sirolimus-eluting stent (CoCr-SES).. From March 2009 to February 2010, a total of 5,084 patients from 83 centres who were eligible to receive CoCr-SES were enrolled in the FOCUS registry. The primary endpoint was 12-month major adverse cardiac events (MACE, defined as the composite of cardiac death, myocardial infarction [MI], and target vessel revascularisation [TVR]). One-year data were available for 5,013 (98.6%) of the 5,084 patients enrolled. The primary endpoint occurred in 174 (3.47%) of 5,013 patients, consisting of 43 (0.86%) cardiac deaths, 132 (2.63%) MI, and 46 (0.92%) TVR. According to the Academic Research Consortium definition, definite and probable stent thrombosis (ST) occurred in 0.52% (26/5,013) of patients, including 19 cases of early ST and 7 of late ST. The 12-month MACE rates were 3.73% and 2.60% for extended-use and standard-use patients, respectively (p=0.065).. The second-generation CoCr-SES was associated with low rates of 12-month MACE and ST in a broad spectrum of patients, thereby confirming the clinical safety and efficacy of this stent in a real-world setting.

Topics: Aged; Antibiotics, Antineoplastic; China; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Equipment Failure; Female; Humans; Indonesia; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Registries; Retreatment; Sirolimus; Thailand; Treatment Outcome

Meta-analysis of randomized trials showed superior efficacy and similar safety of drug-eluting stent over bare-metal stent in acute ST-elevation myocardial infarction (STEMI) patients. However, long-term relative outcomes of sirolimus- (SES) vs. paclitaxel-eluting stent (PES) have not been fully evaluated in randomized studies. This study compared long-term safety and efficacy of these two stents in STEMI.. A total of 308 STEMI patients were randomly treated with SES (n = 154) or PES (n = 154). Three-year clinical outcomes were assessed. Primary outcome of interest was incidence of major adverse cardiac events (MACE) including death, myocardial infarction (MI), stent thrombosis or target vessel revascularization (TVR). Secondary outcome of interest was occurrence of very late stent thrombosis.. Both groups had similar baseline characteristics. During follow-up, there was no difference between the two groups in terms of death (6.5% for SES and 10.4% for PES, p = 0.22), MI (2.6% vs. 3.9%, p = 0.75), stent thrombosis (1.9% vs. 3.2%, p = 0.72), TVR (3.9% vs. 8.4%, p = 0.15) and MACE (12.3% vs. 18.8%, p = 0.12). Eight patients in overall population had stent thrombosis: definite 3, probable 1, and possible 4. Cumulative incidence of stent thrombosis was gradually increased; 0.6% at 30 days, 0.6% at 1 year, 1.6% at 2 years, and 2.6% at 3 years. Very late stent thrombosis, definite or probable, occurred in 0.6% for both.. Among non-selected STEMI patients who underwent primary angioplasty, both SES and PES might be safe and SES showed similar three-year clinical outcomes compared to PES.

Topics: Angioplasty, Balloon, Coronary; Cause of Death; Coronary Restenosis; Disease-Free Survival; Drug-Eluting Stents; Electrocardiography; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Tubulin Modulators

The aims of this study were to identify the efficacy of optimal stent expansion (OSE) according to the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study) criteria in drug-eluting stent (DES) and compare paclitaxel-eluting stent (PES) to sirolimus-eluting stent (SES).. Although poststent high-pressure balloon dilatation is proposed after bare metal stent implantation according to OSE, defined by the criteria of the MUSIC Study, very little data are available in DES.. Two hundred fifty patients (M:F = 149:101; age, 61.5 ± 9.2 years) who underwent 9-month follow-up angiography in the Poststent Optimal Stent Expansion Trial (POET) were included in this study. We assessed angiographic in-stent restenosis (ISR) and neointima volume (NV) using IVUS at 9 months.. At 9-month follow up, there were no significant differences in ISR and NV index (NV/stent length, mm(2) ) between patients with and without OSE. However, the rate of ISR and NV index were higher in PES [ISR: 18 (13.7%) and 4 (3.4%), P = 0.004; NV index: 1.02 ± 0.99 mm(2) and 0.21 ± 0.37, P < 0.001 in PES and SES].. OSE according to the MUSIC Study criteria was not related to ISR and NV in the DES era but PES had a significantly higher ISR rate and NV than SES after poststent high-pressure balloon dilatation.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Paclitaxel; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Republic of Korea; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

This prospective, open-label multicenter study was conducted to assess the pharmacokinetics of Biolimus A9 after elution from BioMatrix II coronary stents. Recent clinical trials have demonstrated the efficacy and safety of Biolimus A9 eluted from different stent platforms. To date, the pharmacokinetics of Biolimus A9 in patients following the deployment of BioMatrix II stents has not yet been studied. BioMatrix II stents were implanted into 27 patients with coronary artery disease. The primary endpoints of the study were the systemic concentrations of Biolimus A9 after 28 days and 6 months as measured using a sensitive validated liquid chromatography-tandem mass spectrometry assay.. The highest measured blood concentration at any time point was 394 pg/mL. At 28 days and 6 months following stent placement, 51.8 and 100% of patients, respectively, had Biolimus A9 concentrations <10 pg/mL. After 9 months, 100% of the patients were free of major cardiac adverse events (MACE). There was no Biolimus A9 toxicity, no cardiac or non-cardiac deaths, no myocardial infarctions, nor target vessel or target lesion revascularizations during the 9 months of follow-up. No case of acute, subacute, or late stent thrombosis was detected.. Compared to other drug-eluting stents, such as Cypher, BioMatrix II results in relatively low systemic exposure, which may be explained by the ablominal coating of the Biomatrix II stent in combination with Biolimus A9's high lipophilicity.

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Sirolimus; Treatment Outcome

Long-term outcomes after sirolimus-eluting stent (SES) implantation in haemodialysis (HD) patients have remained controversial. We investigated the impact of HD on outcomes after SES implantation.. We analysed the data on 2050 patients who underwent SES implantation in a multi-centre prospective registry in Japan. Three-year clinical outcomes were compared between the HD group (n = 106) and the non-haemodialysis (NH) group (n = 1944). At the 3-year clinical follow-up, the rates of unadjusted cardiac mortality (HD: 16.3 vs. NH: 2.3%) and target-lesion revascularization (TLR) (HD: 19.4 vs. NH: 6.6%) were significantly higher in the HD group than the NH group (P < 0.001). Although HD group had a numerically higher stent thrombosis rate, the difference in stent thrombosis between the two groups (HD: 2.0 vs. NH: 0.7%) did not reach statistical significance. Using Cox's proportional-hazard models with propensity score adjustment for baseline differences, the HD group had higher risks of TLR [HD: 16.3 vs. NH: 6.1%; hazard ratio, 2.83; 95% confidence interval (CI): 1.62-4.93, P = 0.0003] and cardiac death (HD: 12.3 vs. NH: 2.3%; hazard ratio, 5.51; 95% CI: 2.58-11.78, P < 0.0001). The consistent results of analyses, whether unadjusted or adjusted for other baseline clinical and procedural differences, identify HD as an independent risk factor for cardiac death and TLR.. Percutaneous coronary intervention with SES in HD patients has a higher incidence of repeat revascularization and mortality compared with those in NH patients. Haemodialysis appears to be strongly associated with mortality and repeat revascularization even after SES implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Prospective Studies; Registries; Renal Dialysis; Retreatment; Sirolimus; Treatment Outcome

Recent trials with different designs indicated that drug-eluting stents may be superior to vascular brachytherapy (VBT) for the treatment of in-stent restenosis (ISR). We performed a randomised, double-centre, clinical, quantitative coronary angiographic (QCA) and intravascular ultrasound (IVUS) acute and 3-years comparison of 90Sr/90Y-VBT and sirolimus-eluting stent implantation (SES) for ISR.. Ninety-one (91) consecutive patients were included. By QCA, SES led to a higher acute gain (2.08 ± 0.41 mm vs. 1.54 ± 0.70 mm, p < 0.0001), higher postprocedural minimum lumen diameter (2.76 ± 0.39 mm vs. 2.39 ± 0.52 mm; p < 0.0001), lower late lumen loss at follow-up (0.09 ± 0.29 vs. 0.39 ± 0.79 mm, p = 0.042), and a higher net lumen gain of the target lesion (2.05 ± 0.51 vs 1.18 ± 1.08 mm, p < 0.0001). By IVUS, the smaller acute gain following VBT was the result of residual intima hyperplasia, the intima hyperplasia formation following SES was extremely low, and the edge-effect was virtually absent after SES, respectively. At 6-month follow-up, both the angiographic restenosis rate (4.7 vs. 22.7%; p < 0.0001) and target lesion revascularisation rate (2.3 vs. 10.4%; p = 0.025) were lower in SES. Importantly, SES showed a stable clinical course at 3-year follow-up while VBT was associated with a sustained incidence of target vessel failure (11.6 vs. 46.7%; p < 0.0001).. SES for ISR is associated with superior QCA, IVUS and clinical results at 6-month and 3-year of follow-up when compared with VBT.

Topics: Aged; Angioplasty, Balloon, Coronary; Brachytherapy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Strontium Radioisotopes; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Yttrium Radioisotopes

The safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the Taxus Express(2) paclitaxel-eluting stent (PES) has been demonstrated through 2 years in the SPIRIT II and III randomized clinical trials, but limited longer-term data have been reported. In the SPIRIT III trial, 1,002 patients with up to 2 lesions in 2 coronary arteries were randomized 2:1 to EESs versus PESs at 65 United States sites. At completion of 3-year follow-up, treatment with EES compared to PES resulted in a significant 30% decrease in the primary clinical end point of target vessel failure (cardiac death, myocardial infarction, or ischemic-driven target vessel revascularization, 13.5% vs 19.2%, hazard ratio 0.70, 95% confidence interval 0.50 to 0.96, p = 0.03) and a 43% decrease in major adverse cardiovascular events, cardiac death, myocardial infarction, or ischemic-driven target lesion revascularization (9.1% vs 15.7%, hazard ratio 0.57, 95% confidence interval 0.39 to 0.83, p = 0.003). In a landmark analysis, major adverse cardiovascular events were decreased to a similar extent with EES compared to PES 0 through 1 year and 1 year through 3 years (hazard ratio 0.56, 95% confidence interval 0.35 to 0.90; hazard ratio 0.59, 95% confidence interval 0.31 to 1.11, respectively). In conclusion, patients treated with EES rather than PES in the SPIRIT III trial had significantly improved event-free survival at 3 years. From 1 year to 3 years hazard curves continued to diverge in favor of EES, consistent with an improving long-term safety and efficacy profile of EES compared to PES, with no evidence of late catchup.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Logistic Models; Male; Middle Aged; Paclitaxel; Prospective Studies; Single-Blind Method; Sirolimus; Survival Rate; Treatment Outcome; Tubulin Modulators; United States

The purpose of this randomized study was to compare sirolimus-eluting stenting with coronary artery bypass grafting (CABG) for patients with unprotected left main (ULM) coronary artery disease.. CABG is considered the standard of care for treatment of ULM. Improvements in percutaneous coronary intervention (PCI) with use of drug-eluting stents might lead to similar results. The effectiveness of drug-eluting stenting versus surgery has not been established in a randomized trial.. In this prospective, multicenter, randomized trial, 201 patients with ULM disease were randomly assigned to undergo sirolimus-eluting stenting (n = 100) or CABG using predominantly arterial grafts (n = 101). The primary clinical end point was noninferiority in freedom from major adverse cardiac events, such as cardiac death, myocardial infarction, and the need for target vessel revascularization within 12 months.. The combined primary end point was reached in 13.9% of patients after surgery, as opposed to 19.0% after PCI (p = 0.19 for noninferiority). The combined rates for death and myocardial infarction were comparable (surgery, 7.9% vs. stenting, 5.0%; noninferiority p < 0.001), but stenting was inferior to surgery for repeat revascularization (5.9% vs. 14.0%; noninferiority p = 0.35). Perioperative complications including 2 strokes were higher after surgery (4% vs. 30%; p < 0.001). Freedom from angina was similar between groups (p = 0.33).. In patients with ULM stenosis, PCI with sirolimus-eluting stents did not show noninferiority [corrected] to CABG at 12-month follow-up with respect to freedom from major adverse cardiac events, which is mainly influenced by repeated revascularization, whereas for hard endpoints, [corrected] PCI results are favorable. A longer follow-up is warranted. [corrected]

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Radiography; Sirolimus; Treatment Outcome

The present study aimed to investigate the difference in major adverse cardiac events (MACE) at 12 months in patients with coronary bifurcation lesions after double kissing double crush (DK crush) or provisional stenting (PS) techniques.. Provisional side branch (SB) stenting is preferable to DK crush because it has been associated with fewer complications. It is unknown which strategy would provide the best results.. From April 2007 to June 2009, 370 unselected patients with coronary bifurcation lesions from 7 Asian centers were randomly assigned to either the DK or the PS group. Additional SB stenting in PS was required if final results were suboptimal. The primary end point was the occurrence of MACE at 12 months, including cardiac death, myocardial infarction, or target vessel revascularization (TVR). Secondary end point was the angiographic restenosis at 8 months.. There were 3 procedural occlusions of SB in the PS group. At 8 months, angiographic restenosis rates in the main vessel and SB were significantly different between the DK (3.8% and 4.9%) and the PS groups (9.7% and 22.2%, p = 0.036 and p < 0.001, respectively). Additional SB stenting in the PS group was required in 28.6% of lesions. TVR was 6.5% in the DK group, occurring significantly less often than in the PS group (14.6%, p = 0.017). There were nonsignificant differences in MACE and definite stent thrombosis between the DK (10.3% and 2.2%) and PS groups (17.3%, and 0.5%, p = 0.070 and p = 0.372, respectively).. DK crush was associated with a significant reduction of TLR and TVR in this unselected patient population. However, there was no significant difference in MACE between DK and the PS groups. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChicTR-TRC-00000015).

Topics: Age Factors; Aged; Angioplasty, Balloon, Coronary; China; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Hospital Mortality; Humans; Male; Middle Aged; Prospective Studies; Prosthesis Failure; Risk Assessment; Severity of Illness Index; Sex Factors; Sirolimus; Survival Analysis; Time Factors; Treatment Outcome

The aim of this study was to investigate the efficacy of a paclitaxel-eluting balloon (PEB) for the treatment of sirolimus-eluting stent (SES) restenosis.. Because drug-eluting stents (DES) are being used in increasingly complicated settings, DES restenosis is no longer an uncommon phenomenon, and its optimal treatment is unknown.. This study was a prospective single-blind randomized trial conducted in 50 patients with SES restenosis. Patients were randomly assigned to a PEB group (n = 25) or a conventional balloon angioplasty (BA) group (n = 25). The primary end point was late lumen loss at 6-month follow-up. Secondary end points included the rate of binary restenosis (in-segment analysis) and major adverse cardiac events (MACE) at 6-month follow-up.. At 6-month angiographic follow-up (follow-up rate: 94%), in-segment late lumen loss was lower in the PEB group than in the BA group (0.18 ± 0.45 mm vs. 0.72 ± 0.55 mm; p = 0.001). The incidence of recurrent restenosis (8.7% vs. 62.5%; p = 0.0001) and target lesion revascularization (4.3% vs. 41.7%; p = 0.003) was also lower in the PEB group than in the BA group. The cumulative MACE-free survival was significantly better in the PEB group than in the BA group (96% vs. 60%; p = 0.005).. In patients with SES restenosis, PEB provided much better clinical, angiographic outcomes than conventional BA.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Disease-Free Survival; Drug-Eluting Stents; Female; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Prospective Studies; Risk Assessment; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

In the Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents (ISAR-TEST-4) trial, we demonstrated the noninferiority of biodegradable polymer (BP) sirolimus-eluting stent to permanent polymer (PP) sirolimus/everolimus-eluting stent (Cypher/Xience-V) on the basis of clinical outcomes. In this study, we compare the antirestenotic efficacy of these stents in ISAR-TEST-4 patients with paired angiographic studies.. Patients with de novo coronary lesions in native vessels (excluding left main lesions) were randomly assigned to receive a BP stent or a PP stent. Endpoints of interest of this study were in-stent late lumen loss, in-segment binary restenosis, and restenosis morphology at 6-8-month follow-up angiogram.. Of the 2,603 patients (3,372 lesions) enrolled in ISAR TEST-4 trial, 2,016 patients (2,637 lesions) underwent repeat angiographic examination 6-8 months after randomization: 1,006 patients (1,323 lesions) treated with BP stents and 1,010 patients (1,314 lesions) treated with PP stents. No difference was observed between BP and PP stents in in-stent late lumen loss (0.24 ± 0.6 vs. 0.26 ± 0.5 mm, respectively, P = 0.49) or in in-segment binary restenosis (11.6% [153 lesions] vs. 11.8% [155 lesions], P = 0.85). Focal pattern of restenosis was observed in the majority of patients receiving either BP or PP stents. The diffuse pattern of restenosis was observed in 26.8% of patients treated with BP stent and 26.5% of patients treated with PP stent (P = 0.79).. Angiographic characteristics of restenosis after BP-based limus-eluting stents are similar to those of PP-based limus-eluting stents.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

In the RESOLUTE All Comers trial, the Resolute zotarolimus-eluting stent was non-inferior to the Xience V everolimus-eluting stent for the primary stent-related endpoint of target lesion failure (cardiac death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation) at 1 year. However, data for long-term safety and efficacy from randomised studies of new generation drug-eluting coronary stents in patients treated in routine clinical practice are scarce. We report the prespecified 2-year clinical outcomes from the RESOLUTE All Comers trial.. In 2008, patients with at least one coronary lesion 2.25-4.0 mm in diameter, with greater than 50% stenosis, were randomly assigned to a Resolute zotarolimus-eluting stent or a Xience V everolimus-eluting stent at 17 centres in Europe and Israel. Randomisation was by an interactive voice response system stratified by centre. Study investigators were not masked to treatment allocation; but those who did data management and analysis, and patients were masked. There were no restrictions as to the number of vessels or lesions treated, or the number of stents implanted. We assessed prespecified safety and efficacy outcomes at 2 years with specific focus on patient-related composite (all death, all myocardial infarction, all revascularisation) and stent-related composite outcomes. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00617084.. 1140 patients were assigned to the zotarolimus-eluting stent and 1152 to the everolimus-eluting stent; 1121 and 1128 patients, respectively, completed 2-year follow-up. The patient-related outcome (231 [20.6%] zotarolimus vs 231 [20.5%] everolimus; difference 0.1%, 95% CI-3.2 to 3.5; p=0.958) and stent-related outcome (126 [11.2%] vs 121 [10.7%]; difference 0.5%, -2.1 to 3.1; p=0.736) did not differ between groups, although rates of the stent-related outcome were substantially lower than were those for the patient-related outcome. Three patients in each group (0.3%) had very late (after 1 year) stent thrombosis.. Similar safety and efficacy outcomes were sustained between two new generation drug-eluting stents at 2-year follow-up. The greater number of patient-related than stent-related events in patients with complex clinical and lesion characteristics emphasises that during long-term follow-up, the optimisation of secondary prevention is at least as important as the selection of which new generation drug-eluting stent to implant in a specific lesion.. Medtronic (USA).

Topics: Adult; Aged; Confounding Factors, Epidemiologic; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Death, Sudden, Cardiac; Drug-Eluting Stents; Europe; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Israel; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Prospective Studies; Secondary Prevention; Sirolimus; Treatment Outcome

The RESOLUTE US (R-US) trial is a prospective, observational study designed to evaluate the clinical effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in a U.S. population.. The R-ZES releases zotarolimus over a 6-month period in order to achieve optimal clinical effectiveness and safety.. The R-US trial recruited patients with de novo native coronary lesions suitable for 1- or 2-vessel treatment with stents from 2.25 to 4.0 mm in diameter. In the main analysis cohort (2.5- to 3.5-mm stents and single-lesion treatment), the primary endpoint was 12-month target lesion failure (TLF) defined as the composite of cardiac death, myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR), compared with data from Endeavor zotarolimus-eluting stent (E-ZES) trials, adjusting for baseline covariates through propensity scores.. Overall, 1,402 patients were enrolled with a mean reference vessel diameter of 2.59 ± 0.47 mm and diabetes prevalence of 34.4%. In the main analysis cohort, TLF was 3.7% at 12 months compared with historical E-ZES results (TLF = 6.5%). The R-ZES met the 3.3% margin of noninferiority (rate difference = -2.8%, upper 1-sided 95% confidence interval: -1.3%, p < 0.001). The overall TLF rate was 4.7%, and rates of cardiac death, MI, and TLR were 0.7%, 1.4%, and 2.8%, respectively. The 12-month rate of stent thrombosis was 0.1%.. The R-ZES achieved a very low rate of clinical restenosis while maintaining low rates of important clinical safety events such as death, MI, and stent thrombosis at 1-year follow-up. (The Medtronic RESOLUTE US Clinical Trial [R-US]; NCT00726453).

Topics: Aged; Cohort Studies; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prevalence; Prospective Studies; Sirolimus; Treatment Outcome; United States

This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents.. The SXscore can identify patients treated with PCI who are at highest risk of adverse events.. The SXscore was calculated prospectively in 2,033 of the 2,292 patients enrolled in the RESOLUTE All Comers study (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention). Clinical outcomes in terms of a patient-oriented composite endpoint (POCE) of all-cause death, myocardial infarction (MI), and repeat revascularization; the individual components of POCE; target lesion failure (TLF) (a composite of cardiac death, target-vessel MI, and clinically driven target lesion revascularization); and stent thrombosis were subsequently stratified according to SXscore tertiles: SXscore(LOW) ≤ 9 (n = 698), 9 17 (n = 659).. At 12-month follow-up, rates of POCE, MI, repeat revascularization, TLF, and the composite of death/MI were all significantly higher in patients in the highest SXscore tercile. Rates of stent thrombosis were all highest in the SXscore(HIGH) tertile (p > 0.05). After multivariate adjustment, the SXscore was identified as an independent predictor of POCE, MI, repeat revascularization, and TLF (p < 0.05 for all). At 12-month follow-up, the SXscore, ACEF score, and Clinical SXscore had C-statistics of 0.57, 0.78, and 0.67, respectively, for mortality and of 0.62, 0.56, 0.63, respectively, for POCE. No significant between-stent differences were observed for TLF or POCE in any of the SXscore tertiles.. The SYNTAX score is able to stratify risk amongst an all-comers population treated with PCI with second-generation drug-eluting stents (DES); however, improvements can be made with the inclusion of clinical variables. (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention; NCT00617084).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Europe; Everolimus; Female; Health Status Indicators; Humans; Israel; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Survival Rate; Time Factors; Treatment Outcome

The objective of the study was to assess noninferiority of the polymer-free sirolimus-eluting Yukon Choice stent (Translumina GmbH, Hechingen, Germany) compared with the polymer-based Taxus Liberté stent (Boston Scientific, Natick, Massachusetts) with regard to the primary endpoint, in-stent late lumen loss, at 9 months in patients with diabetes mellitus.. The Yukon Choice stent has been evaluated in several randomized controlled trials before, albeit to date, there has been no trial that exclusively enrolled patients with diabetes mellitus.. Patients with diabetes mellitus undergoing percutaneous coronary intervention for clinically significant de novo coronary artery stenosis were randomized 1:1 to receive either the polymer-free sirolimus-eluting Yukon Choice stent or the polymer-based paclitaxel-eluting Taxus Liberté stent.. A total of 240 patients were randomized. Quantitative coronary angiography was available for 79% of patients. Mean in-stent late lumen loss was 0.63 ± 0.62 mm for the Yukon Choice stent and 0.45 ± 0.60 mm for the Taxus Liberté stent. Based on the pre-specified margin, the Yukon Choice stent failed to show noninferiority for the primary endpoint. During follow-up, there were no significant differences between groups regarding death, myocardial infarction, stent thrombosis, target lesion revascularization, target vessel revascularization, or nontarget vessel revascularization.. Compared with the Taxus Liberté stent, the polymer-free sirolimus-eluting Yukon Choice stent failed to show noninferiority with regard to the primary endpoint, in-stent late lumen loss, in patients with diabetes mellitus after 9-month follow-up. Both stents showed comparable clinical efficacy and safety. (Yukon Choice Versus Taxus Liberté in Diabetes Mellitus; NCT00368953).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Germany; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Polymers; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

The purpose of this study was to compare the safety and efficacy of the Xience V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) with the Taxus Liberté (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) at 2-year follow-up.. COMPARE (Comparison of the everolimus eluting XIENCE-V stent with the paclitaxel eluting TAXUS LIBERTÉ stent in all-comers: a randomized open label trial) demonstrated a superior clinical outcome of EES over PES at 1 year in all comers. Whether this superiority is maintained after discontinuation, at 12 months, of dual antiplatelet therapy is unclear.. Patients undergoing percutaneous coronary intervention with limited exclusion criteria were randomly allocated to EES or PES. The 2-year pre-specified endpoints are composites of safety and efficacy and stent thrombosis.. Follow-up was completed in 1,795 of 1,800 patients (99.7%). The groups had similar baseline characteristics. At 2 years, significantly fewer EES patients took dual antiplatelet therapy (11.4% vs. 15.4%, p = 0.02). The primary composite of all death, nonfatal myocardial infarction, and target vessel revascularization occurred in 9.0% of EES patients and 13.7% of PES patients (relative risk [RR]: 0.66; 95% confidence interval [CI]: 0.50 to 0.86) driven by a lower rate of myocardial infarction (3.9% vs. 7.5%; RR: 0.52; 95% CI: 0.35 to 0.77) and target vessel revascularization (3.2% vs. 8.0%; RR: 0.41; 95% CI: 0.27 to 0.62), in parallel with a lower rate of definite or probable stent thrombosis (0.9% vs. 3.9%; RR: 0.23; 95% CI: 0.11 to 0.49). Differences significantly increased between 1- and 2-year follow-up for the primary composite endpoint (p = 0.04), target vessel revascularization (p = 0.02), and definite or probable stent thrombosis (p = 0.02).. The substantial clinical benefit of the EES over the PES with regard to measures of both safety and efficacy is maintained at 2 years in real-life practice with an increasing benefit in terms of safety and efficacy between 1 year and 2 years.

Topics: Administration, Oral; Adolescent; Adult; Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Follow-Up Studies; Humans; Immunosuppressive Agents; Middle Aged; Paclitaxel; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Tubulin Modulators

We sought to determine whether the differences in outcomes present between everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV trial at 1 year were sustained with longer-term follow-up.. In the SPIRIT IV trial, patients undergoing percutaneous coronary intervention who were randomized to EES compared with PES experienced lower 1-year rates of target lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target lesion revascularization [TLR]), with significant reductions in the individual rates of MI, TLR, and stent thrombosis.. We prospectively randomized 3,687 patients with up to 3 noncomplex previously untreated native coronary artery lesions to EES versus PES at 66 U.S. sites. Follow-up through 2 years is complete in 3,578 patents (97.0%).. Treatment with EES compared with PES reduced the 2-year rates of TLF (6.9% vs. 9.9%, p = 0.003), all MI (2.5% vs. 3.9%, p = 0.02), Q-wave MI (0.1% vs. 0.8%, p = 0.002), stent thrombosis (0.4% vs. 1.2%, p = 0.008), and ischemia-driven TLR (4.5% vs. 6.9%, p = 0.004), with nonsignificantly different rates of all-cause and cardiac mortality. Between 1 year and 2 years, there were no significant differences in adverse event rates between the 2 stent types.. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, the benefits of EES compared with those of PES present at 1 year were sustained at 2 years.

Topics: Adolescent; Adult; Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Follow-Up Studies; Humans; Immunosuppressive Agents; Middle Aged; Paclitaxel; Prospective Studies; Sirolimus; Thrombosis; Treatment Outcome; Tubulin Modulators

This study sought to compare late safety and efficacy outcomes following percutaneous coronary revascularization with zotarolimus-eluting stents (ZES) and sirolimus-eluting stents (SES).. Despite higher late lumen loss and binary restenosis with ZES compared with SES, it is uncertain whether differences in early angiographic measures translate into more disparate late clinical events.. Clinical outcomes were prospectively evaluated through 5 years in the ENDEAVOR III (A Randomized Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Cypher Sirolimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) that randomized 436 patients of relatively low anatomic and clinical risk to treatment with ZES (n = 323) or SES (n = 113) and evaluated a primary endpoint of 8-month angiographic late lumen loss.. At 5 years (completeness of follow-up: 95.2%), pre-specified endpoints of all-cause mortality (5.2% vs. 13.0%, p = 0.02), myocardial infarction (1.0% vs. 4.6%, p = 0.03), and the composite event rates of cardiac death/myocardial infarction (1.3% vs. 6.5%, p = 0.009) and major adverse cardiac events (14.0% vs. 22.2%, p = 0.05) were significantly lower among patients treated with ZES. Rates of target lesion (8.1% ZES vs. 6.5% SES, p = 0.68) and target vessel revascularization were similar between treatment groups. Stent thrombosis was infrequent and similar in both groups (0.7% ZES vs. 0.9% SES, p = 1.0). Between 9 months and 5 years, progression of major adverse cardiac events was significantly more common with SES than with ZES (16.7% vs. 7.8%, p = 0.015).. Despite initially higher angiographic late lumen loss, rates of clinical restenosis beyond the protocol-specified angiographic follow-up period remain stable with ZES compared with the rates for SES, resulting in similar late-term efficacy. Over 5 years, significant differences in death, myocardial infarction, and composite endpoints favored treatment with ZES. (The Medtronic Endeavor III Drug Eluting Coronary Stent System Clinical Trial [ENDEAVOR III]; NCT00217256).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

First-generation drug-eluting stents have been proved to be very effective for the treatment of bare metal stent in-stent restenosis (BMS ISR). The efficacy of second-generation drug-eluting stents in this setting remains less well defined. The present study compared the long-term clinical outcome after treatment of BMS ISR using the second-generation everolimus-eluting stent (EES) to that after treatment using the paclitaxel-eluting stent (PES). A total of 174 patients with BMS ISR underwent percutaneous coronary intervention using a PES (95 patients) or an EES (79 patients) from 2003 to 2010. The patients in the PES and EES groups were followed up for 42.2 ± 22.2 and 18.3 ± 8.2 months, respectively. The primary end point of the study was survival free of major adverse cardiac events at 1 year. The secondary end points were survival free of the need for revascularization of the target lesion and definite stent thrombosis. The baseline clinical and angiographic parameters were comparable between the 2 groups. The freedom from major adverse cardiac event rate at 1 year of follow-up was 4.5% and 13.6% (p = 0.0663) for the EES and PES groups, respectively. The target lesion revascularization (TLR) rates were greater in the PES group at 1 year of follow-up compared to the EES group (1% vs 11.5%, p = 0.0193). The rate of myocardial infarction, death, and definite stent thrombosis for the EES and PES groups at 1 year of follow-up was 0% versus 4.2% (p = 0.0984), 3% versus 2.1% (p = 0.6855), and 0% versus 2.1% (p = 0.2382), respectively. The use of a PES for treatment of ISR was the only independent predictor of recurrent TLR at 1 year of follow-up (odds ratios 1.11, 95% confidence interval 1.05 to 1.18; p = 0.0193). During the complete follow-up period, the rates of TLR, myocardial infarction, death, major adverse cardiac events, and definite stent thrombosis were not different between the 2 treatment groups. In conclusion, EES resulted in reduced rates of TLR at 1 year of follow-up compared to PES when used for treatment of BMS ISR. However, at long-term follow-up, the event rates between EES and PES were comparable after treatment of BMS ISR.

Topics: Aged; Angioplasty; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Treatment Outcome

Age is an important determinant of outcomes in patients treated with percutaneous coronary intervention (PCI). This report from the randomised multicentre SPIRIT III trial compares the outcomes in elderly and younger patients treated with everolimus-eluting stent (EES) versus paclitaxel-eluting stent (PES).. A total of 1,002 patients with stable or unstable angina or inducible ischaemia undergoing PCI were randomised in a 2:1 ratio to receive EES or PES. Outcomes were examined across the randomised groups as a function of age and stent type. Patients ≥65 years of age (elderly) treated with EES vs. PES had lower in-segment late lumen loss (0.11±0.32 mm vs. 0.38±0.55 mm, respectively, p=0.0002) and lower rates of binary in-segment restenosis (3.4% vs. 15.5%, p = 0.004) at eight months, along with a 48% lower incidence of 3-year target vessel failure (TVF=cardiac death, myocardial infarction and ischaemia-driven target vessel revascularisation [TVR]; 10.8% vs. 20.8%, p=0.009), mainly due to a lower incidence of TVR (5.4% vs. 9.2%, p=0.20). Among EES patients, elderly compared to younger patients had comparable rates of binary in-segment restenosis (3.4% vs. 5.6%, p=0.44) at eight months but paradoxically lower rates of TVF (10.8% vs. 17.1%, p=0.03) at three years. Among PES patients, elderly compared to younger patients had a higher rate of binary in-segment restenosis (15.5% vs. 3.4%, p=0.01) at eight months and no difference in the rate of 3-year TVF (20.8% vs. 19.4%, p=0.77) .There was a significant interaction between stent assignment, age ≥65 years and 8-month angiographic in-segment late loss (p=0.001).. Implantation of both EES and PES appeared to be safe in elderly patients, however EES compared to PES was more effective due to enhanced 3-year MACE- and TVF-free outcomes. Further research should clarify age-specific mechanisms of neointimal response after treatment with drug-eluting stents.

Topics: Age Factors; Aged; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Laser-Assisted; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Incidence; Longitudinal Studies; Male; Myocardial Ischemia; Paclitaxel; Risk Factors; Sirolimus; Treatment Outcome

Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to neointimal hyperplasia (NIH). The aim of this study was to use quantitative coronary angiography (QCA) and volumetric intravascular ultrasound (IVUS) to evaluate the effects of the sirolimus-eluting Cypher® stent (SES) and the zotarolimus-eluting Endeavor® stent (ZES) on angiographic late lumen loss and intima hyperplasia in diabetic patients.. In the DiabeDES III trial, 127 patients were randomised to SES or ZES stent implantation. Angiographic 10-month follow-up data were available in 105 patients, including 48 SES and 57 ZES treated patients. Angiographic endpoints were in-stent late lumen loss and minimal lumen diameter. IVUS endpoints included NIH volume and in-stent percent volume obstruction. Baseline clinical characteristics and lesion parameters were similar in the two groups. At 10-month follow-up, angiographic in-stent late lumen loss (0.14±0.37 mm vs. 0.74±0.45 mm, p<0.001) was reduced and minimum lumen diameter was higher (2.36±0.53 mm vs. 1.96±0.65, p<0.001) in the SES group as compared to the ZES group. As compared to the ZES group, NIH volume was significantly reduced in the SES group (median [interquartile range]: 0.0 mm3 [0.0 to 1.2] vs. 16.5 mm3 [6.2 to 31.1], p<0.001). In-stent% volume obstruction was significantly reduced in SES as compared to ZES (median [interquartile range]: 0.0% [0.0-0.7] vs. 13.0% [6.7-20.8], p<0.001).. In diabetic patients, the SES reduced angiographic late lumen loss and inhibited NIH more effectively than ZES.

Topics: Aged; Angioplasty, Balloon, Laser-Assisted; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Neointima; Risk Factors; Single-Blind Method; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Stents may be undersized during primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis. We sought to compare the reference vessel diameter (RVD) of the infarct-related artery before, immediately after, and at late follow-up after PCI for STEMI. We further investigated whether vessels treated with paclitaxel-eluting (PES) or bare-metal stents (BMS) behave differently with respect to RVD at follow-up.. From the HORIZONS-AMI trial, we identified 2,974 patients (3,589 lesions) with complete quantitative angiographic data for stent implantation (2,233 treated with PES and 741 treated with BMS).. Considering all lesions, the median RVD was 2.87 mm (25th-75th percentile 2.54-3.22 mm) at baseline, 2.92 mm (2.58-3.28 mm) immediately post-PCI, and 2.88 mm (2.55-3.22 mm) after 13 months (1,197 patients; P = .001 pre vs post, P = .06 post vs follow-up, and P = .21 pre vs follow-up). There were no significant differences between the RVD for PES versus BMS at any period. The maximal stent or balloon size was 3.00 mm (3.00-3.50 mm) for both groups. There were no differences in RVD at baseline or post-PCI between patients with and without stent thrombosis.. Reference vessel diameter does not change substantially from baseline to follow-up, irrespective of stent type. Stent diameter was appropriate for vessel size. The RVD of patients with and without stent thrombosis was similar at baseline and post-PCI. Thus, the high rates of stent thrombosis after primary PCI for STEMI cannot be attributed to stent undersizing.

Topics: Aged; Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Postoperative Period; Prosthesis Design; Sirolimus; Treatment Outcome

Inconsistent results in outcomes have been observed between the genders after drug-eluting stent implantation. The aim of this study was to investigate gender differences in neointimal proliferation for the Endeavor zotarolimus-eluting stent (ZES) and the Driver bare-metal stent (BMS). A total of 476 (n = 391 ZES, n = 85 BMS) patients whose volumetric intravascular ultrasound analyses were available at 8-month follow-up were studied. At 8 months, neointimal obstruction and maximum cross-sectional narrowing (CSN) were significantly lower in women than in men receiving ZES (neointimal obstruction 15.5 ± 9.5% vs 18.2 ± 10.9%, p = 0.025; maximum CSN 30.3 ± 13.2% vs 34.8 ± 15.0%, p = 0.007). Conversely, these parameters tended to be higher in women than in men receiving BMS (neointimal obstruction 36.3 ± 15.9% vs 27.5 ± 17.2%, p = 0.053; maximum CSN 54.3 ± 18.6% vs 45.6 ± 18.3%, p = 0.080). There was a significant interaction between stent type and gender regarding neointimal obstruction (p = 0.001) and maximum CSN (p = 0.003). Multivariate linear regression analysis revealed that female gender was independently associated with lower neointimal obstruction (p = 0.027) and maximum CSN (p = 0.004) for ZES but not for BMS. Compared to BMS, ZES were independently associated with a reduced risk for binary restenosis in both genders (odds ratio for women 0.003, p = 0.001; odds ratio for men 0.191, p <0.001), but the magnitude of this risk reduction with ZES was significantly greater in women than men (p = 0.015). In conclusion, female gender is independently associated with decreased neointimal hyperplasia in patients treated with ZES. The magnitude of risk reduction for binary restenosis with ZES is significantly greater in women than in men.

Topics: Angioplasty, Balloon, Coronary; California; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Myocardial Infarction; Neointima; Prognosis; Prosthesis Design; Retrospective Studies; Risk Factors; Sex Distribution; Sex Factors; Sirolimus

Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus.. This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23 ± 0.27 versus 0.37 ± 0.52 mm; difference, -0.13 mm; 95% confidence interval, -0.25 to -0.02; upper 1-sided 95% confidence interval, -0.04; P<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%; P=0.029) and in-segment restenosis (0.9% versus 6.5%; P=0.035). However, in-stent late loss (0.11 ± 0.26 versus 0.20 ± 0.49 mm; P=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%; P=0.317), death (1.3% versus 3.3%; P=0.448), and myocardial infarction (0% versus 1.3%; P=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%; P=0.218), were also not statistically different between the 2 groups.. Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease.

Topics: Adolescent; Adult; Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Sirolimus; Treatment Outcome; Young Adult

The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).. The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the "all-comers" LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 816 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046).. The SXscore when applied to an "all-comers" patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Heart Diseases; Humans; Male; Middle Aged; Polymers; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence; Treatment Outcome

This study sought to assess the temporal course of neointimal hyperplasia (NIH) formation following implantation of 2 different generations of drug-eluting stents (DES).. The amount of NIH following DES implantation correlates with the potency of the antiproliferative drug, its kinetic release, as well as some individual characteristics, as the presence of diabetes mellitus (DM). Recently, some publications have suggested a continuous growth of NIH following DES, which in some cases, might result in late "catch-up.". Twenty-five patients with single, de novo lesions were treated with sirolimus-eluting stents (SES) (n = 12) and biolimus-eluting stents (BES) (n = 13) and underwent intravascular ultrasound evaluation immediately after the procedure and at 9-month and 5-year follow-ups. The primary endpoint was the comparison of the percentage of NIH obstruction between mid- and long-term follow-up.. Mean age was 59 years and 28% of patients had DM. Overall, the percentage of NIH obstruction significantly increased from 9 months to 5 years (1.3% at first follow-up vs. 4.8% at second follow-up, p = 0.002). There was no significant difference in the variation of vessel volume (Δ = -0.70 mm(3)/mm BES vs. Δ = 0.18 mm(3)/mm SES, p = 0.56), lumen volume (Δ = 0.40 mm(3)/mm BES vs. Δ = -0.05 mm(3)/mm SES, p = 0.71), and percentage of NIH obstruction (Δ = 3.0% BES vs. Δ = 3.8% SES, p = 0.55) among DES. However, diabetic patients had a marked NIH increase along the years (NIH volume at second follow-up: 10.15 mm(3) DM vs. 5.11 mm(3) non-DM, p = 0.028).. The present serial intravascular ultrasound assessment supports the occurrence of continuous NIH growth following different generations of DES. These findings seem to be particularly more pronounced among patients with DM.

Topics: Clopidogrel; Coronary Angiography; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Risk Factors; Sirolimus; Statistics as Topic; Statistics, Nonparametric; Ticlopidine; Time Factors; Ultrasonography, Interventional

This study sought to compare the clinical outcomes of everolimus-eluting stents (EES) versus paclitaxel-eluting stents (PES) in patients with acute coronary syndromes (ACS) and stable coronary artery disease (CAD).. Although randomized trials have shown superiority of EES to PES, the safety and efficacy of EES in ACS is unknown.. We performed a patient-level pooled analysis from the prospective, randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV, and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) trials in which 2,381 patients with ACS and 4,404 patients with stable CAD were randomized to EES or to PES. Kaplan-Meier estimates of death, myocardial infarction (MI), ischemia-driven target lesion revascularization, and stent thrombosis were assessed at 2 years and stratified by clinical presentation (ACS vs. stable CAD).. At 2 years, patients with ACS compared with stable CAD had higher rates of death (3.2% vs. 2.4%, hazard ratio [HR]: 1.37 [95% confidence interval (CI): 1.02 to 1.85], p = 0.04) and MI (4.9% vs. 3.4%, HR: 1.45 [95% CI: 1.14 to 1.85], p = 0.02). In patients with ACS, EES versus PES reduced the rate of death or MI (6.6% vs. 9.3%, HR: 0.70 [95% CI: 0.52 to 0.94], p = 0.02), stent thrombosis (0.7% vs. 2.9%, HR: 0.25 [95% CI: 0.12 to 0.52], p = 0.0002), and ischemia-driven target lesion revascularization (4.7% vs. 6.2%, HR: 0.69 [95% CI: 0.48 to 0.99], p = 0.04). In patients with stable CAD, EES reduced the rate of death or MI (4.5% vs. 7.1%, HR: 0.62 [95% CI: 0.48 to 0.80], p = 0.0002), stent thrombosis (0.7% vs. 1.8%, HR: 0.34 [95% CI: 0.19 to 0.62], p = 0.0002), and ischemia-driven target lesion revascularization (3.9% vs. 6.9%, HR: 0.55 [95% CI: 0.42 to 0.73], p < 0.0001).. Treatment with EES versus PES provides enhanced safety and efficacy regardless of the acuity of the clinical syndrome being treated and appears to mitigate the increased risk of stent thrombosis associated with ACS. (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions [SPIRIT II]; NCT00180310; SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT III]; NCT00180479; SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions [SPIRIT IV]; NCT00307047; A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: the COMPARE Trial [COMPARE]; NCT01016041).

Topics: Acute Coronary Syndrome; Antineoplastic Agents, Phytogenic; Confidence Intervals; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Netherlands; Odds Ratio; Paclitaxel; Sirolimus; Time Factors; Treatment Outcome; United States

This study compared everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) for long coronary lesions.. Outcomes remain relatively unfavorable for stent-based coronary intervention of lesions with long diseased segments.. This randomized, multicenter, prospective trial compared the use of long EES with SES in 450 patients with long (≥ 25 mm) native coronary lesions. The primary endpoint of the trial was in-segment late luminal loss at 9-month angiographic follow-up.. The EES and SES groups had similar baseline characteristics. Lesion length was 34.0 ± 15.4 mm in the EES group and 34.3 ± 13.5 mm in the SES group (p = 0.85). Nine-month angiographic follow-up was performed in 80% of the EES group and 81% of the SES group (p = 0.69). In-segment late loss as the primary study endpoint was significantly larger in the EES group than in the SES group (0.17 ± 0.41 mm vs. 0.09 ± 0.30 mm, p for noninferiority = 0.96, p for superiority = 0.04). The in-segment binary restenosis rate was also higher in the EES group than in the SES group (7.3% vs. 2.7%, p = 0.046). However, in-stent late loss (0.22 ± 0.43 mm vs. 0.18 ± 0.28 mm, p = 0.29) and in-stent binary restenosis rate (3.9% vs. 2.7%, p = 0.53) were similar among the 2 groups. The incidence of any clinical outcomes (death, myocardial infarction, stent thrombosis, target lesion revascularization, and composite outcomes) was not statistically different between the 2 groups.. For patients with long native coronary artery disease, EES implantation was associated with greater angiographic in-segment late loss and higher rates of in-segment restenosis compared with SES implantation. However, clinical outcomes were both excellent and not statistically different.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Recurrence; Sirolimus; Statistics as Topic; Time Factors

The goal of this study was to compare the angiographic outcomes of everolimus-eluting stents (EES) and sirolimus-eluting stents (SES) in a head-to-head manner.. EES have been shown to be superior to paclitaxel-eluting stents in inhibiting late loss (LL) and clinical outcome. Whether EES may provide similar angiographic and clinical outcomes compared with SES is undetermined.. This was a prospective, randomized, open-label, multicenter trial to demonstrate the noninferiority of EES compared with SES in preventing LL at 9 months. A total of 1,443 patients undergoing percutaneous coronary intervention were randomized 3:1 to receive EES or SES. Routine follow-up angiography was recommended at 9 months. The primary endpoint was in-segment LL at 9 months, and major secondary endpoints included in-stent LL at 9 months, target lesion failure, cardiac death, nonfatal myocardial infarction, target lesion revascularization, and stent thrombosis at 12 months. Data were managed by an independent management center, and clinical events were adjudicated by an independent adjudication committee.. Clinical follow-up was available in 1,428 patients and angiographic follow-up in 924 patients (1,215 lesions). The primary endpoint of the study (in-segment LL at 9 months) was 0.11 ± 0.38 mm and 0.06 ± 0.36 mm for EES and SES, respectively (p for noninferiority = 0.0382). The in-stent LL was also noninferior (EES 0.19 ± 0.35 mm; SES 0.15 ± 0.34 mm; p for noninferiority = 0.0121). The incidence of clinical endpoints was not statistically different between the 2 groups, including target lesion failure (3.75% vs. 3.05%; p = 0.53) and stent thrombosis (0.37% vs. 0.83%; p = 0.38).. EES were noninferior to SES in inhibition of LL after stenting, which was corroborated by similar rates of clinical outcomes. (Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting [EXCELLENT]; NCT00698607).

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Prosthesis Failure; Sirolimus

The optimal treatment of bare metal stent restenosis is still not defined. The most employed contemporary option is the implantation of a drug-eluting stent (DES). However, this procedure implies the addition of a second metal layer in the vessel wall, which is linked to delayed healing. Furthermore, there may be a increased risk of malapposition of both struts of the bare metal and the newly implanted drug-eluting stent. These phenomena may give rise to an increased risk of stent thrombosis in this patient population. Recently, drug-eluting balloons (DEB) have been proposed as a new treatment strategy for bare metal stent restenosis. The initial results of this technique look promising.. To compare healing processes after treatment of bare metal stent (BMS) in-stent restenosis (ISR) with balloon dilatation using DEB versus implantation of DES.. This is a prospective, multicentre (University Hospitals Leuven and ZOL Hospital Genk, Belgium) randomised clinical trial with clinical, angiographic and OCT follow-up at nine months. Patients with bare metal stent restenosis and an indication for repeat PCI are randomised to treatment with a paclitaxel-eluting balloon (SeQuent Please, B-Braun, Melsungen, Germany) versus a Xience V/ Xience Prime everolimus-eluting stent (Abbott Vascular, Santa Clara, CA, USA). The primary objective of this study is to evaluate the vascular healing response of the vessel wall after balloon angioplasty with a paclitaxel-eluting balloon versus implantation of a drug-eluting stent in patients with in-stent restenosis in a coronary artery. The primary endpoint of the study is stent strut coverage and stent strut apposition at nine months, as assessed with OCT.. Currently no prospectively collected data on vessel wall healing after treatment of in-stent restenosis, whether with DES or with DEB, are available. Therefore, the SEDUCE trial will yield pivotal insights on this important topic and guide further optimisation of the interventional treatment for this condition.

Topics: Angioplasty, Balloon, Coronary; Belgium; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Equipment Design; Everolimus; Humans; Metals; Paclitaxel; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Research Design; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Safety concerns regarding use of drug-eluting stent systems (DES) are related mostly to late stent thrombosis, which is facilitated by incomplete stent endothelial coverage. Specific information about time course and amount of endothelial strut coverage of different DES is required, in order to further refine the concept of antiplatelet therapy after DES implantation. Optical coherence tomography (OCT) is emerging as a new gold standard for endovascular imaging of stents, atherosclerosis progression, vulnerable plaque, and neointimal proliferation. The aim of this study is a comparative evaluation using OCT of the XIENCE V everolimus-eluting stent (Abbot Vascular, Santa Clara, CA, USA) on one hand, and the bare metal stent Coroflex Blue postdilated with the paclitaxel-eluting balloon Sequent Please (both from B Braun Melsungen AG, Melsungen, Germany) on the other hand, with respect to endothelial coverage and neointimal proliferation.. Eighty patients scheduled for elective percutaneous coronary intervention (PCI) of a native coronary stenosis suitable for DES implantation and OCT imaging are scheduled to be openly randomised 1:1 to either XIENCE or Coroflex Blue/Sequent Please. The study is conducted prospectively at a university high-volume PCI centre with OCT expertise. Angiographic follow-up and time-domain OCT imaging with motorised pull-back at 1 mm/s are planned six months after study stent implantation in all patients. OCT endpoints are: (1) endothelial coverage, expressed as % of struts without coverage and % of stent length containing non-covered struts, and respectively (2) neointimal proliferation, given as % neointimal volumetric proliferation within the whole stent and also as peak focal % neointimal area proliferation. The study is not powered for clinical endpoints, which are: subacute or late stent thrombosis and need for revascularisation of the stent segment. Given the high number of measurements (15 cross-section images / 1 mm stent length), OCT endpoints are likely to reach significance at the level p <0.05, if the drop-out rate in follow-up does not exceed 20%.. The study is currently on-going and its termination is scheduled for February 2010. (ClinicalTrials.gov identifier: NCT01056744).

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Endothelial Cells; Everolimus; Germany; Humans; Metals; Paclitaxel; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Research Design; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Tunica Intima

To assess the efficacy of the sirolimus-eluting stent when implanted in smaller caliber vessels using three-dimensional intravascular ultrasound (IVUS) analysis.. One hundred and twenty-three patients (69 sirolimus-coated Bx Velocity and 54 control) who underwent successful three-dimensional IVUS at follow up comprised this IVUS substudy from the SIRIUS (SIRolImUS-coated Bx Velocity stent in the treatment of patients with de novo coronary artery lesions) population. To evaluate the impact of vessel size, 2 groups were created using QCA reference vessel diameter (RVD; large vessel group: RVD>/=2.75 mm and small vessel group: RVD<2.75 mm).. Sirolimus-eluting stents significantly reduced neointimal hyperplasia by the same relative magnitude within the stent in small vessels as well as in large vessels. Although sirolimus-eluting stents had favorable effects on lumen area at stent edges in larger vessels, the effect was less in smaller vessels, especially at the proximal edge. IVUS-detected adverse vessel response, such as late-acquired incomplete apposition, did not increase in smaller vessels even with relatively higher dose exposure.. Sirolimus-eluting stents showed inhibition of neointimal hyperplasia in small vessels compared to bare metal stents with no increase of vascular complications.

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Hyperplasia; Imaging, Three-Dimensional; Immunosuppressive Agents; Sirolimus; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Although oxidative stress plays an important role in the pathophysiology of restenosis, its role following the implantation of sirolimus-eluting stents (SES) is unknown.. We examined the relation between total peroxides (TP), a marker of oxidative stress, and in-stent late luminal loss over a 6-month follow-up in patients with stable coronary artery disease and compared the results from SES with those from bare metal stents (BMS). We enrolled 75 consecutive patients, who underwent successful PCI and were randomly allocated to SES (n=37) or BMS (n=38). Blood samples were taken 24 h before, at 24 h, 48 h and 1 month after angioplasty; levels of TP were determined on each occasion. Follow-up coronary angiography was performed 6-8 months later.. TP levels in the BMS group were significantly higher at 24 h and 48 h compared to baseline (p=0.006 for both). At one month there was a significant decline from the 48 h levels (p=0.029) to levels slightly, but not significantly higher than baseline. In contrast, in SES TP levels showed no significant changes during the first 48 h, while they declined to levels somewhat lower than baseline at 30 days. A significant correlation was found between TP changes and in-stent late luminal loss at 6 months in both groups.. Our study showed that patients with stable coronary artery disease who received SES have a different behavior of oxidative stress after stenting compared with BMS, and this could contribute to the difference in restenosis rate between these 2 types of stents.

Topics: Aged; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Metals; Middle Aged; Oxidative Stress; Sirolimus; Stents; Treatment Outcome

Treatment of restenosis following intracoronary brachytherapy (ICB) is still a challenging problem. Implantation of sirolimus-eluting stents (SES) in this setting may be an option to be evaluated.. We analysed the prospective multicentre SES registry, the German Cypher Stent Registry. 7,445 patients treated with an SES during percutaneous coronary intervention (PCI) were registered. Out of these patients, 61 (0.8%) were treated for restenosis after ICB: 56 patients with completed follow-up could be evaluated. Median age was 65 years, with 80% male patients. 48% of patients had a prior myocardial infarction and 25% had already coronary bypass surgery (CABG). Type B2 lesion was present in 40% and type C lesion in 22.4%. Event rates from SES implantation until 6.6 months follow-up were death 0%, myocardial infarction 3.6%, stroke 2.1%. Target vessel revascularization rate (TVR) was 16.4%, and major adverse cardiovascular or cerebral events (MACCE) or TVR occurred in 17.9% of patients. This TVR rate was higher compared with that of other patients treated with an SES: 8.4% (P = 0.04). During 65 months follow-up MACCE or TVR occurred in 44.6% of patients.. The treatment of lesions after ICB occurred in 0.8% out of all patients treated with an SES. Clinical event rates during early follow-up were low. However, the TVR rate was 16.4%, which was significantly higher when compared with other SES-treated patients (8.4%, P = 0.04). The treatment of restenosis after ICB with SES seems to be safe and reasonably effective; however, there might be a late catch-up phenomenon.

Topics: Aged; Blood Vessel Prosthesis; Brachytherapy; Coronary Restenosis; Drug-Eluting Stents; Female; Germany; Humans; Male; Middle Aged; Prevalence; Prospective Studies; Registries; Risk Assessment; Risk Factors; Sirolimus; Treatment Outcome

To establish the efficacy of oral rapamycin at a dose of 2 mg for 1 month at reducing the 6-month restenosis rate after the implantation of bare metal stents.. A prospective, 1:1 randomized, single-blind, placebo-controlled study was conducted in 108 consecutive patients assigned immediately after stent implantation to oral rapamycin (4 mg loading dose followed by 2 mg daily for 30 days) or a placebo.. Rapamycin was maintained in 98% of patients. Angiographic in-stent binary restenosis was 14.3% in the rapamycin group versus 32.1% in the placebo group, with a relative risk (RR) of 0.45 (95% CI 0.24-0.84, p = 0.015). The rapamycin blood concentration at 15 days correlated with binary restenosis (p = 0.044). The volume obstructions found by intravascular ultrasound for the rapamycin and the placebo groups were 18.1+/-10.7 and 27.1+/-15.7% (p = 0.002), respectively. Major adverse cardiac events at a 5-year follow-up were 31.5% for the rapamycin group and 50.0% for the placebo group (RR 0.63, 95% CI 0.39-1.01, p = 0.078).. Oral rapamycin significantly reduces the incidence of restenosis at follow-up compared to a placebo.We believe these findings deserve further testing in larger trials.

Topics: Administration, Oral; Aged; Antibiotics, Antineoplastic; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Single-Blind Method; Sirolimus; Stents; Ultrasonography, Interventional

Incomplete endothelialization has been found to be associated with late stent thrombosis, a rare but devastating phenomenon, more frequent after drug-eluting stent implantation. Optical coherence tomography (OCT) has 10 times greater resolution than intravascular ultrasound and thus appears to be a valuable modality for the assessment of stent strut coverage. The LEADERS trial was a multi-centre, randomized comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer. This study sought to evaluate tissue coverage and apposition of stents using OCT in a group of patients from the randomized LEADERS trial.. Fifty-six consecutive patients underwent OCT during angiographic follow-up at 9 months. OCT images were acquired using a non-occlusive technique at a pullback speed of 3 mm/s. Data were analysed using a Bayesian hierarchical random-effects model, which accounted for the correlation of lesion characteristics within patients and implicitly assigned analytical weights to each lesion depending on the number of struts observed per lesion. Primary outcome was the difference in percentage of uncovered struts between BESs and SESs. Twenty patients were included in the analysis in the BES group (29 lesions with 4592 struts) and 26 patients in the SES group (35 lesions with 6476 struts). A total of 83 struts were uncovered in the BES group and 407 out of 6476 struts were uncovered in the SES group [weighted difference -1.4%, 95% confidence interval (CI) -3.7 to 0.0, P = 0.04]. Results were similar after adjustment for pre-procedure lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap. There were three lesions in the BES group and 15 lesions in the SES group that had > or =5% of all struts uncovered (difference -33.1%, 95% CI -61.7 to -10.3, P < 0.01).. Strut coverage at an average follow-up of 9 months appears to be more complete in patients allocated to BESs when compared with SESs. The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determined.

Topics: Absorbable Implants; Coronary Restenosis; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Polymers; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Tubulin Modulators

Drug-eluting stents (DES) are widely used for treatment of coronary artery disease with benefit of reduced restenosis compared to bare metal stents. The XIENCE VEverolimus Eluting Coronary Stent System is a second-generation DES system for better deliverability while maintaining safety and efficacy profiles. The present pharmacokinetic sub-study from the SPIRIT III Randomized and Controlled Trial (RCT) was to evaluate systemic exposure of patients to everolimus and to further demonstrate safety following implantation of XIENCE Vstents with everolimus doses ranging from 53 to 181 microg.. Drug concentrations in whole blood were determined at multiple time points using a validated analytical method with a limit of quantification of 0.1 ng/mL. Individual C(max) ranged from 0.17 to 2.40 ng/mL and occurred between 0.07 and 1.88 hours across all dose levels. Both mean and individual C(max) values were below the trough blood concentrations of everolimus (Certican) for inhibition of organ transplant rejection. The last time point at which drug concentrations could be quantified ranged from 12 to 168 hours postimplantation in individual patients. In most cases, the blood levels dropped below the limit of quantification after 72 hours.. This study confirms that the XIENCE Vstent causes a limited and systemic exposure to everolimus. The presumed localized and efficient delivery of everolimus to target vessels coupled with limited and transient systemic drug exposure contributes to the safety and effectiveness of the XIENCE VEECSS in patients of SPIRIT III RCT for longer than 2 years.

Topics: Aged; Analysis of Variance; Area Under Curve; Confidence Intervals; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Linear Models; Male; Middle Aged; Sirolimus

The aim of this study was to assess the role of short oral administration of rapamycin, without loading dose, in the reduction of restenosis rate after bare metal stent implantation.. Previous studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation.. This was prospective, open-label study of 80 patients randomized to either oral rapamycin (2 mg/day for 30 days, starting within 24 hr of stent implantation) or no therapy after implantation of a coronary bare metal stent. The primary study end point was incidence of angiographic binary restenosis and late loss at six months. The secondary end points were target lesion revascularization (TLR), target vessel revascularization (TVR), and incidence of major adverse cardiovascular events (MACE) at 6 months.. Angiographic follow up was completed in 72/80 (90%) of patients. In the rapamycin group, the drug was well tolerated (22.5% minor side effects) and was maintained in 100% of patients. At six months, the in-segment binary restenosis was 10.5% in rapamycin group vs. 51.4% in no-therapy group, P < 0.001) and the in-stent binary restenosis was 7.9% in rapamycin group vs. 48.7% in no-therapy group, P < 0.001. The in-segment late loss was also significantly reduced with oral therapy (0.29 + or - 0.39 vs. 0.86 + or - 0.64 mm, respectively, P < 0.001). Similarly, after six months, patients in the oral rapamycin group also showed a significantly lower incidence of TLR and TVR (7% vs. 22.7%, respectively, P = 0.039) and MACE (7% vs. 22.7%, respectively, P = 0.039).. This study showed that the administration of oral rapamycin (2 mg/day, without loading dose) during 30 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Topics: Administration, Oral; Aged; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Secondary Prevention; Sirolimus; Stents

To investigate the clinical impact of the following observations in the randomized SPIRIT II and III trials: an incremental increase in in-stent neointima between 1 and 2 years with the everolimus-eluting stent (EES) but not with the paclitaxel-eluting stent (PES) in SPIRIT II; a tendency of lower stent thrombosis in EES than in PES among those who first discontinued a thienopyridine after 6 months.. A pooled analysis was performed using the 2-year clinical data from the SPIRIT II and III trials randomizing a total of 1302 patients with de novo coronary artery lesions either to EES or to PES. Inclusion and exclusion criteria were comparable between two trials. Major adverse cardiac event (MACE) was defined as cardiac death, myocardial infarction, or ischaemia-driven target lesion revascularization (TLR). At 2 years, MACE rates were 7.1% in EES vs. 12.3% in PES, respectively (log-rank P = 0.0014), without late increase in TLR. Among those who first discontinued a thienopyridine after 6 months, Academic Research Consortium (ARC) definite or probable stent thrombosis was 1.1% in EES vs. 1.3% in PES (P = 1.00).. The benefits of EES in reducing TLR were robust between 6 months and 2 years. No significant difference in the thrombosis rate among those who first stopped a thienopyridine after 6 months was observed.

Topics: Aged; Cell Proliferation; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Sirolimus; Treatment Outcome; Tubulin Modulators

The aim of this study was to investigate whether the reported favorable 1-year outcome of the sirolimus-eluting stent (SES) versus the bare-metal stent (BMS) in the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent In Acute Myocardial Infarction) trial, in the setting of ST-segment elevation myocardial infarction (STEMI), is maintained at 3-year follow-up.. At present, only long-term registry data, but not randomized trials, on the safety and effectiveness of SES in STEMI patients are available.. Overall, 320 STEMI patients were randomized to receive SES or BMS. The primary end point was the incidence of major adverse cardiovascular events (MACE), at 3-year follow-up. The secondary end points were the rate of target lesion revascularization (TLR) and target vessel revascularization (TVR) and target vessel failure (TVF). The incidence of late events, starting from clopidogrel withdrawal, was also investigated.. The 3-year incidence of MACE was lower in the SES group compared with the BMS group (12.7% vs. 21%, p = 0.034), as were TLR (7% vs. 13.5%, p = 0.048), TVR (8% vs. 16%, p = 0.027), and TVF (11.5% vs. 20.5%, p = 0.028) rates. The 3-year survival rate free from MACE, TLR, and TVF was significantly higher in the SES group than in the BMS group (87%, 93%, and 89.5% vs. 79%, 86.5%, and 79.5%, respectively, p < 0.05). The lower incidence of adverse events in the SES group was driven by TLR reduction and achieved in the first year of follow-up. The cumulative incidence of death and recurrent myocardial infarction, starting from clopidogrel discontinuation, was comparable in the 2 groups.. The clinical benefits of SES have been shown to be greater than those of BMS at 3-year follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Sirolimus; Time Factors; Treatment Outcome

For patients with sirolimus-eluting stent (SES) restenosis requiring reintervention, we compared a strategy of repeat SES (Cypher, Cordis, Miami Lakes, Florida) implantation with paclitaxel-eluting stent (PES) (Taxus, Boston Scientific, Natick, Massachusetts) implantation.. Despite their high anti-restenotic efficacy, the widespread utilization of SES therapy has led to a significant absolute number of patients presenting with SES treatment failure. The optimal treatment strategy for such patients remains unclear.. The ISAR-DESIRE 2 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis 2) study was a randomized, open-label, active-controlled trial conducted among 450 patients with clinically significant in-SES restenosis at 2 centers in Munich, Germany. After pre-treatment with 600 mg clopidogrel, all patients were randomly assigned to either SES or PES implantation. The primary end point was late lumen loss, based on in-stent analysis, at 6- to 8-month follow-up angiography. Secondary end points were binary angiographic restenosis (diameter stenosis >50%) at 6- to 8-month follow-up, target lesion revascularization, the composite of death or myocardial infarction, and definite stent thrombosis at 12 months.. Regarding anti-restenotic efficacy, there were no differences between SES and PES in late loss (0.40 +/- 0.65 mm vs. 0.38 +/- 0.59 mm; p = 0.85), binary restenosis (19.6% vs. 20.6%; p = 0.69), or target lesion revascularization (16.6% vs. 14.6%; p = 0.52). In terms of safety outcomes, the rates of death/myocardial infarction (6.1% vs. 5.8%; p = 0.86) and stent thrombosis (0.4% vs. 0.4%; p > 0.99) were also similar.. In cases of SES restenosis, treatment with either repeat SES or switch to PES was associated with a comparable degree of efficacy and safety. Drug resistance at an individual patient level may play a contributory role to the somewhat higher than expected late loss observed with the SES in the current study. (Intracoronary Stenting and Angiographic Results: Drug-Eluting Stents for In-Stent Restenosis 2 [ISAR-DESIRE 2]; NCT00598715).

Topics: Aged; Antineoplastic Agents, Phytogenic; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Myocardial Revascularization; Paclitaxel; Retrospective Studies; Secondary Prevention; Sirolimus; Treatment Outcome

In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery disease who were receiving routine clinical care with no direct follow-up.. We did a single-blind, all-comer superiority trial in adult patients with chronic stable coronary artery disease or acute coronary syndromes, and at least one target lesion. Patients were treated at one of five percutaneous coronary intervention centres between January, 2006, and August, 2007. Computer-generated block randomisation and a telephone allocation service were used to randomly assign patients to receive the zotarolimus-eluting or the sirolimus-eluting stent. Data for follow-up were obtained from national Danish administrative and health-care registries. The primary endpoint was a composite of major adverse cardiac events within 9 months: cardiac death, myocardial infarction, and target vessel revascularisation. Intention-to-treat analyses were done at 9-month and 18-month follow-up. This trial is registered with ClinicalTrials.gov, number NCT00660478.. 1162 patients (1619 lesions) were assigned to receive the zotarolimus-eluting stent, and 1170 patients (1611 lesions) to receive the sirolimus-eluting stent. 67 patients (72 lesions) had stent failure, and six patients were lost to follow-up. All randomly assigned patients were included in analyses at 9-month follow-up; 2200 patients (94%) had completed 18-month follow-up by the time of our assessment. At 9 months, the primary endpoint had occurred in a higher proportion of patients treated with the zotarolimus-eluting stent than in those treated with the sirolimus-eluting stent (72 [6%] vs 34 [3%]; HR 2.15, 95% CI 1.43-3.23; p=0.0002). At 18-month follow-up, this difference was sustained (113 [10%] vs 53 [5%]; 2.19, 1.58-3.04; p<0.0001). For patients receiving the zotarolimus-eluting stent and those receiving the sirolimus-eluting stent, all cause-mortality was similar at 9-month follow-up (25 [2%] vs 18 [2%]; 1.40, 0.76-2.56; p=0.28), but was significantly different at 18-month follow-up (51 [4%] vs 32 [3%]; 1.61, 1.03-2.50; p=0.035).. The sirolimus-eluting stent is superior to the zotarolimus-eluting stent for patients receiving routine clinical care.. Cordis and Medtronic.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Retreatment; Single-Blind Method; Sirolimus; Thrombosis; Treatment Outcome

In the ISAR-TEST-2 (Intracoronary Stenting and Angiographic Results: Test Efficacy of Three Limus-Eluting Stents) randomized trial, a new-generation sirolimus- and probucol-eluting stent (Dual-DES) demonstrated a 12-month efficacy that was comparable to sirolimus-eluting stents (SES) (Cypher, Cordis Corp., Warren, New Jersey) and superior to zotarolimus-eluting stents (ZES) (Endeavor, Medtronic CardioVascular, Santa Rosa, California). The aim of the current study was to investigate the comparative clinical and angiographic effectiveness of SES, Dual-DES, and ZES between 1 and 2 years.. Long-term polymer residue is implicated in adverse events associated with delayed vessel healing after drug-eluting stent therapy. The second-generation ZES utilizes an enhanced biocompatibility polymer system whereas a new-generation Dual-DES employs a polymer-free drug-release system.. A total of 1,007 patients undergoing coronary stenting of de novo lesions in native vessels were randomized to treatment with SES (n = 335), Dual-DES (n = 333), or ZES (n = 339). Clinical follow-up was performed to 2 years. Angiographic follow-up was scheduled at 6 to 8 months and 2 years.. There were no significant differences between groups regarding death/myocardial infarction (SES: 10.2% vs. Dual-DES: 7.8% vs. ZES: 9.2%; p = 0.61) or definite stent thrombosis (SES: 0.9% vs. Dual-DES: 0.9% vs. ZES: 0.6%; p = 0.87). Two-year target lesion revascularization (TLR) was 10.7%, 7.7%, and 14.3% lesions in the SES, Dual-DES, and ZES groups, respectively (p = 0.009). Incident TLR between 1 and 2 years in the Dual-DES group (0.9%) was significantly lower than in the Cypher SES group (3.6%) (p = 0.009), but comparable to the Endeavor ZES group (0.7%) (p = 0.72). These findings mirrored those observed for binary restenosis.. At 2 years, there was no signal of a differential safety profile between the 3 stent platforms. Furthermore, the antirestenotic efficacy of both Dual-DES and ZES remained durable between 1 and 2 years, with Dual-DES maintaining an advantage over the entire 2-year period. (Intracoronary Stenting and Angiographic Results: Test Efficacy of Three Limus-Eluting Stents [ISAR-TEST-2]; NCT00332397).

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Polymers; Probability; Prospective Studies; Prosthesis Design; Prosthesis Failure; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Survival Analysis; Time Factors; Treatment Outcome

Drug-eluting stents have shown to be superior over bare metal stents in clinical and angiographic outcomes after percutaneous treatment of coronary artery stenosis. However, long-term follow-up data are scarce and only available for sirolimus- and paclitaxel-eluting stents.. To assess the feasibility and performance of the XIENCE V everolimus-eluting stent (EES) versus an identical bare metal stent after a 5-year follow-up period.. SPIRIT FIRST was a First in Man, multicentre, prospective, single-blind, clinical trial, randomizing 60 patients with a single de novo coronary artery lesion in a ratio of 1:1 to either an everolimus eluting or a bare metal control stent.. At 5-year clinical follow-up, data were available in 89% and 86% of patients in the everolimus and control arm, respectively. In the everolimus arm, no additional death, myocardial infarction, clinically driven target lesion revascularization (TLR), or clinically driven target vessel revascularization (TVR) events were observed between 1- and 5-year follow-up. The 5-year hierarchical major adverse cardiac events (MACE) and target vessel failure (TVF) rates for the everolimus arm were 16.7% (4/24) for both endpoints. In the control group, no additional cardiac death, myocardial infarction, or clinically driven TLR events were observed between 2- and 5-year follow-up. No additional clinically driven TVR events were observed between 3- and 5-year follow-up. The 5-year hierarchical MACE and TVF rates for the control arm were 28.0% (7/25) and 36.0% (9/25), respectively. No stent thromboses were observed in either the everolimus arm or the control arm up to 5 years.. The favorable 5-year long term clinical outcome of the EES is consistent with the results from other studies of the EES with shorter follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Europe; Everolimus; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Prospective Studies; Prosthesis Design; Risk Assessment; Severity of Illness Index; Single-Blind Method; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional

This was a single centre registry study on clinical efficacy and safety of drug-eluting stent (DES) in diabetic patients undergoing percutaneous coronary intervention (PCI) for complex coronary lesions.. A total of 288 diabetic patients who underwent elective PCI between September 2003 and June 2006 in our centre were enrolled and followed-up for 18 months. Among them, 79 (27.4%) patients received sirolimus-eluting stent (SES), 138 (47.9%) paclitaxel-eluting stent (PES) and 71 (24.7%) zotarolimus-eluting stent (ZES). The endpoints were major adverse cardiac events (MACE) and stent thrombosis rates.. Baseline demographics were comparable among the 3 DES groups (median age was 60 years; 69% men). Complex lesions (defined as ACC/AHA type C stenosis) accounted for 55.6% of the total lesions: SES (50.6%), PES (65.2%) and ZES (43.7%), P = 0.005. At 18 months follow-up, the composite endpoint of MACE was found in 12.7% in SES group, 8.7% in the PES group, 12.7% in ZES group and (P = 0.55). Stent thrombosis (ST) occurred in 1 patient (1.3%) in the SES group, 2 patients (1.4%) in PES group and 1 patient (1.4%) in ZES group, respectively (P = 1.00).. The use of DES for elective PCI in diabetic patients was associated with favourable intermediate-term clinical outcomes with no significant differences in efficacy among the 3 groups. Stent thrombosis had low event occurrence rate.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Sirolimus; Survival Analysis; Treatment Outcome

Chronic total coronary occlusions constitute a sub-group of lesions at very high risk of restenosis after successful percutaneous coronary intervention. The sirolimus-eluting coronary stent is the only drugeluting stent that has demonstrated to reduce angiographic restenosis and the need for new revascularisation procedures in comparison with bare-metal stents in randomised clinical trials focusing on these lesions. Everolimus-eluting stents have shown to offer optimal angiographic and clinical outcomes in comparison with bare-metal stents and paclitaxel-eluting stents, but no randomised trials have tested the device in chronic total occlusions. The CIBELES (non-acute Coronary occlusIon treated By EveroLimus- Eluting Stent) will randomise 208 patients with chronic total coronary occlusions in 13 centres from Portugal and Spain to receive everolimus- or sirolimus-eluting coronary stents. The primary endpoint will be angiographic in-stent late loss.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Portugal; Prosthesis Design; Research Design; Single-Blind Method; Sirolimus; Spain; Time Factors; Treatment Outcome

New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration.. In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months.. At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events.. At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.)

Topics: Aged; Coronary Angiography; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Prosthesis Design; Retreatment; Sirolimus; Treatment Failure

The optimal stenting strategy in true coronary artery bifurcation lesions has not been determined. In this study, a strategy of always stenting both the main vessel and the side branch (MV plus SB) was compared with a strategy of stenting the MV only with optional stenting of the SB. Stents used were sirolimus-eluting stents and paclitaxel-eluting stents.. A total of 108 patients with true coronary bifurcation lesions were randomly assigned to either routine stenting with drug-eluting stents (DES) in both the branches (group MV plus SB) or provisional stenting with DES placement in the main branch and DES placement in the SB only if MV stenting alone provided inadequate results (group MV). The primary end points were major adverse cardiac events (MACE) at 8 months, including myocardial infarction, cardiac death, and stent thrombosis or target vessel revascularization by either percutaneous coronary intervention or coronary artery bypass grafting.. Angiographic follow-up revealed 28.91+/-20.43% stenosis of the SB after provisional stenting and 18.93+/-15.34% (P<0.01) after routine stenting. The corresponding binary restenosis rates were 35.2 and 14.8% (P=0.015). SB stents were implanted in 16.7% of patients in the provisional stenting group and 94.4% of patients in the routine stenting group. In the main branch, binary restenosis rates prebifurcation were 11.1% after provisional and 7.4% after routine stenting (P=0.51), whereas binary restenosis rates postbifurcation were 14.8 and 9.3% (P=0.38), respectively. The overall 8-month incidence of target lesion reintervention was 31.5% after provisional and 7.4% after routine stenting (P<0.01), and cumulative MACE were 38.9 and 11.1% (P<0.01), respectively.. Routine stenting significantly improved the MACE outcome of percutaneous coronary intervention in true coronary bifurcation and bifurcation angle of 60 or less lesions as compared with provisional stenting.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; China; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

Little is known about the impact of treatment with drug-eluting stents (DES) on calcified coronary lesions. This analysis sought to assess the safety and efficacy of the XIENCE V everolimus-eluting stent (EES) in patients with calcified or noncalcified culprit lesions.. The study population consisted of 212 patients with 247 lesions, who were treated with EES alone. Target lesions were angiographically classified as none/mild, moderate, or severe grades of calcification. The population was divided into two groups: those with at least one target lesion moderately or severely calcified (the calcified group: 68 patients with 75 calcified lesions) and those with all target lesions having mild or no calcification (the noncalcified group: 144 patients). Six-month and 2-year angiographic follow-up and clinical follow-up up to 3 years were completed.. The baseline characteristics were not significantly different between both groups. When compared with the noncalcified group, the calcified group had significantly higher rates of 6-month in-stent angiographic binary restenosis (ABR, 4.3% vs. 0%, P = 0.03) and ischemia-driven target lesion revascularization (ID-TLR, 5.9% vs. 0%, P = 0.01), resulting in numerically higher major cardiac adverse events (MACE, 5.9% vs. 1.4%, P = 0.09). At 2 years, when compared with the noncalcified group, the calcified group presented higher in-stent ABR (7.4% vs. 0%, P = 0.08) and ID-TLR (7.8% vs. 1.5%, P = 0.03), resulting in numerically higher MACE (10.9% vs. 4.4%, P = 0.12). At 3 years, ID-TLR tended to be higher in the calcified group than in the noncalcified group (8.6% vs. 2.4%, P = 0.11), resulting in numerically higher MACE (12.1% vs. 4.7%, P = 0.12).. The MACE rates in patients treated with EES for calcified lesions were higher than in those for noncalcified lesions, but remained lower than the results of previously reported stent studies. EES implantation in patients with calcified culprit lesions was safe and associated with favorable reduction of restenosis and repeat revascularization. © 2010 Wiley-Liss, Inc.

Topics: Aged; Angioplasty, Balloon, Coronary; Calcinosis; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; India; Kaplan-Meier Estimate; Male; Middle Aged; New Zealand; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

Previous studies suggested that asymmetric stent expansion did not affect suppression of neointimal hyperplasia (NIH) after sirolimus-eluting stents (SES) implantation. The aim of this study was to evaluate the effects of stent eccentricity (SE) on NIH between SES versus paclitaxel-eluting stents (PES) using an intravascular ultrasound (IVUS) analysis from the randomized trial.. Serial IVUS data were obtained from Post-stent Optimal Expansion (POET) trial, allocated randomly to SES or PES. Three different SE (minimum stent diameter divided by maximum stent diameter) were evaluated; SE at the lesion site with maximal %NIH area (SE-NIH), SE at the minimal stent CSA [SE-minimal stent area (SE-MSA)], and averaged SE through the entire stent (SE-mean). We classified each drug-eluting stents (DES) into the concentric (≥ mean SE) and eccentric groups (< mean SE) based on the mean value of SE.. Among 301 enrolled patients, 233 patients [SES (n = 108), PES (n = 125)] underwent a follow-up IVUS. There was no significant correlation between %NIH area and SE-NIH (r = - 0.083, p = 0.391) or SE-MSA (r = - 0.109, p = 0.259) of SES. However, SE-NIH of PES showed a weak but significant correlation with %NIH area (r = 0.269, p < 0.01). As to the associations between SEmean and NIH volume index, SES revealed no significant correlation (r = - 0.001, p = 0.990), but PES showed a weak but significant correlation (r = 0.320, p < 0.01). However, there was no difference in the restenosis rate between the eccentric versus concentric groups of both DES.. This study suggests that lower SE of both SES and PES, which means asymmetric stent expansion, may not be associated with increased NIH.

Topics: Aged; Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Tunica Intima; Ultrasonography, Interventional

The aim of this study was to evaluate the relative efficacy and safety of zotarolimus-eluting stents (ZES) in comparison with the established and widely used sirolimus- (SES) and paclitaxel-eluting stents (PES) in routine clinical practice.. Whether ZES might provide similar clinical and angiographic outcomes in a broad spectrum of patients compared with SES or PES is undetermined.. We performed a single-blind, multicenter, prospectively randomized trial to compare ZES with SES and PES in 2,645 patients undergoing percutaneous coronary intervention. The primary end point was a composite of major adverse cardiac events (MACE) (death, myocardial infarction, and ischemia-driven target vessel revascularization) at 12 months. A noninferiority comparison (ZES vs. SES) and a superiority comparison (ZES vs. PES) were performed for the primary end point.. Baseline clinical and angiographic characteristics were similar in the 3 groups. At 12 months, the ZES group showed noninferior rates of MACE compared with the SES group (10.2% vs. 8.3%, p for noninferiority = 0.01, p for superiority = 0.17) and significantly fewer MACE than the PES group (10.2% vs. 14.1%, p for superiority = 0.01). The incidence of death or myocardial infarction was similar among the groups (ZES vs. SES vs. PES, 5.8% vs. 6.9% vs. 7.6%, respectively, p = 0.31). The incidence of stent thrombosis was significantly lower in the SES group (ZES vs. SES vs. PES, 0.7% vs. 0% vs. 0.8%, respectively, p = 0.02).. In this large-scale, practical randomized trial, the use of ZES resulted in similar rates of MACE compared with SES and in fewer MACE compared with PES at 12 months. (Comparison of the Efficacy and the Safety of Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions; NCT00418067).

Topics: Aged; Cardiovascular Diseases; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Reperfusion; Paclitaxel; Prospective Studies; Single-Blind Method; Sirolimus; Treatment Outcome

We studied a novel sirolimus eluting stent with a bioabsorbable coating (SES) in >3 months old chronic total coronary occlusions (CTO).. Ninety-five patients were randomised to either BMS (n=47) or SES (n=48). The primary endpoints were late lumen loss (LLL) and in-segment restenosis (ISR) after six months. Secondary endpoints were target vessel revascularisation after six and 24 months. Occlusion length (37.6 mm), reference diameter (2.8 mm) as well as the stented segment (45.5 mm) were similar in both groups. Up until six months no death, myocardial infarction or stent thrombosis occurred in either group. Angiographic follow-up (45BMS/46SES): LLL 1.8 mm/0.77 mm (p<0.0001), ISR 60%/17.4% (p<0.0001). In-segment re-occlusion 15.5%/0% and TVR 53.3%/10.8% (p<0.0001). After 24 months: 1 BMS, 2 SES patients died; 0 BMS, 0 SES infarction; 0 BMS, 0 SES stent thrombosis and 3 BMS, 0 SES TVR between six and 24 months. Thus total TVR after 24 months was 60% for BMS and 10.8% for SES (p<0.0001).. The alternative sirolimus-coated stent was shown to reduce the relative risk of restenosis after six months by 71%, and of TVR after 24 months by 82%. Between six and 24 months, neither stent thrombosis occurred, nor repeat revascularisation was required in patients who received a SES.

Topics: Absorbable Implants; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Germany; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

There remains significant concern about the long-term safety of drug-eluting stents (DES). However, bare metal stents (BMS) have been used safely for over two decades. There is therefore a pressing need to explore alternative strategies for reducing restenosis with BMS. This study was designed to examine whether IVUS-guided cutting balloon angioplasty (CBA) with BMS could convey similar restenosis rates to DES.. In the randomised REstenosis reDUction by Cutting balloon angioplasty Evaluation (REDUCE III) study, 521 patients were divided into four groups based on device and IVUS use before BMS (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At follow-up, the IVUS-CBA-BMS group had a significantly lower restenosis rate (6.6%) than the other groups (p=0.016). We performed a quantitative coronary angiography (QCA) based matched comparison between an IVUS-guided CBA-BMS strategy (REDUCE III) and a DES strategy (Rapamycin-Eluting-Stent Evaluation At Rotterdam Cardiology Hospital, the RESEARCH study). We matched the presence of diabetes, vessel size, and lesion severity by QCA. Restenosis (>50% diameter stenosis at follow-up) and target vessel revascularisation (TVR) were examined. QCA-matched comparison resulted in 120-paired lesions. While acute gain was significantly greater in IVUS-CBA-BMS than DES (1.65±0.41 mm vs. 1.28±0.57 mm, p=0.001), late loss was significantly less with DES than with IVUS-CBA-BMS (0.03±0.42 mm vs. 0.80±0.47 mm, p=0.001). However, no difference was found in restenosis rates (IVUS-CBA-BMS: 6.6% vs. DES: 5.0%, p=0.582) and TVR (6.6% and 6.6%, respectively).. An IVUS-guided CBA-BMS strategy yielded restenosis rates similar to those achieved by DES and provided an effective alternative to the use of DES.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Evaluation Studies as Topic; Follow-Up Studies; Humans; Immunosuppressive Agents; Middle Aged; Prospective Studies; Sirolimus

We sought to evaluate the early drug-eluting stent (DES) era, characterized by widespread device use.. Contemporary clinical practice incorporating more selective DES use can only be assessed by understanding the early DES era.. All patients receiving DES during the first 3 waves of the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) Registry (2004-2006) were evaluated. The primary end point was a composite of death, myocardial infarction (MI), and urgent revascularization at discharge and death, MI, or target lesion revascularization (TLR) at 1 year. The composite end point at each time point was compared across waves. Multivariable logistic regression was used for in-hospital outcomes and multivariable Cox regression was used for 1-year end points.. Ninety-two percent of EVENT patients received at least one DES. One third of patients were treated for Acute Coronary Syndromes (ACS) (33.8%), and later waves included lower lesion complexity. Across waves there was more frequent clopidogrel loading, a decrease in heparin and an increase in bivalirudin use (all P < .01). The primary composite end point of in-hospital death, MI or urgent revascularization occurred in 7.2% of patients, and did not differ across waves. Despite remarkably high levels of routine DES usage, the composite end point of death, MI, or TLR at 1 year averaged 13.5% and did not differ across waves. After adjustment, no statistically significant effect of wave on composite bleeding (P = .068) as well as in-hospital TLR (P = .053) was noted. At 1 year, wave was associated with a lower likelihood of TLR in the adjusted model (HR 0.81, P = .03).. The high-adoption DES era was associated with favorable outcomes, decreasing bleeding rates and changes in antithrombotic approach.

Topics: Acute Coronary Syndrome; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Hospital Mortality; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Paclitaxel; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome; United States

The increased frequency of very late (>1 year) stent thrombosis (VLST) has raised concerns with regard to the safety of sirolimus-eluting stents and paclitaxel-eluting stents (PES).. Experimental and preliminary clinical findings with the zotarolimus-eluting stent (ZES) have suggested a favorable safety profile.. The ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial is a single-blind randomized ZES versus PES clinical trial in 1,548 patients with de novo native coronary lesions; the primary end point-9-month target vessel failure-was previously reported, annual clinical follow-up is planned for 5 years, and this report describes the 3-year outcomes.. The ZES compared with PES reduced target vessel failure (12.3% vs. 15.9%, hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.58 to 1.00, p = 0.049), myocardial infarctions (MI) (2.1% vs. 4.9%, HR: 0.44, 95% CI: 0.25 to 0.80, p = 0.005), and cardiac death plus MI (3.6% vs. 7.1%, HR: 0.52, 95% CI 0.32 to 0.82, p = 0.004). Although the overall 3-year rate of Academic Research Consortium definite/probable stent thrombosis did not differ significantly (1.1% vs. 1.7%, HR: 0.67, 95% CI 0.28 to 1.64, p = 0.380), VLST (between 1 and 3 years) was significantly reduced in ZES patients (1 event vs. 11 events; 0.1% vs. 1.6%, HR: 0.09, 95% CI: 0.01 to 0.71, p = 0.004). Ischemia-driven target lesion revascularization at 3 years was similar with ZES versus PES (6.5% vs. 6.1%, HR: 1.10, 95% CI: 0.73 to 1.65, p = 0.662).. Three-year follow-up results from the ENDEAVOR IV trial indicate similar antirestenosis efficacy but improved clinical safety associated with ZES compared with PES, due to significantly fewer peri-procedural and remote MIs associated with fewer VLST events. (A Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions; NCT00217269).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Single-Blind Method; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; United States

To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation.. Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action.. Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Biomarkers; Blood Glucose; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Chemokine CCL2; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug-Eluting Stents; Female; Glycated Hemoglobin; Humans; Hyperplasia; Hypoglycemic Agents; Inflammation Mediators; Insulin; Interleukin-6; Killer Cells, Natural; Lipids; Male; Middle Aged; Myocytes, Smooth Muscle; Pioglitazone; Prospective Studies; Prosthesis Design; Receptors, CCR2; Republic of Korea; Single-Blind Method; Sirolimus; Thiazolidinediones; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Whether drug-eluting stents are effective and safe in patients with moderate renal insufficiency (RI) is unknown. We performed a pooled analysis of data from 3 blinded randomized trials of sirolimus-eluting stents (SESs) versus bare metal stents (BMSs; SIRIUS, C-SIRIUS, E-SIRIUS) that included 1,510 patients. Clinical and angiographic outcomes were stratified by the presence of RI defined by creatinine clearance calculated by the Cockcroft-Gault formula (normal ≥ 90, mild 60 to 89, moderate < 60 ml/min). Patients with baseline creatinine > 3.0 mg/dl were excluded from these trials. Baseline mild RI was present in 517 patients (34.7%, mean creatinine clearance 75.7 ml/min) and moderate RI in 228 patients (15.3%, mean creatinine clearance 47.2 ml/min). Treatment with SESs resulted in lower rates of 8-month angiographic restenosis rates in patients with RI (mild RI 6.7% vs 42.6%, p < 0.001; moderate RI 9.7% vs 39.7%, p < 0.001) and without baseline RI (7.7% vs 37.2%, p < 0.001). One-year target vessel revascularization rates were similarly decreased with SESs in patients with (mild RI 4.7% vs 24.2%, p < 0.001; moderate RI 5.5% vs 26.9%, p < 0.001) and without (8.1% vs 22.4%, p < 0.001) RI, and this benefit was maintained at 5 years. Compared to patients with normal or mild RI, patients with moderate RI had higher rates of overall mortality and cardiac death at 1 year and 5 years (death 2.6% vs 0.6%, p <0.01, and 17.5% vs 6.3%, p < 0.01, at 1 year and 5 years, respectively; cardiac death 1.3% vs 0.2%, p = 0.05, and 6.6% vs 3.4%, p = 0.04, at 1 year and 5 years, respectively). However, there was no differential effect of SESs versus BMSs on any safety end point. In conclusion, patients with moderate RI have a nearly threefold increase in 5-year mortality after percutaneous coronary intervention compared to patients without RI. The effectiveness of SESs in decreasing restenosis compared to BMSs in patients with moderate RI was preserved and rates of death and myocardial infarction were not adversely affected.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Double-Blind Method; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Postoperative Complications; Renal Insufficiency; Severity of Illness Index; Sirolimus; Stents

The rates of side branch occlusion and subsequent periprocedural MI during everolimus-eluting stent (EES) and paclitaxel-eluting stent (PES) placement were examined in the randomised SPIRIT III trial. Periprocedural myocardial infarction (MI) following drug-eluting stent placement is associated with long-term adverse outcomes. Occlusion of side branches may be an important factor contributing to periprocedural MIs. Consecutive procedural angiograms of patients randomly assigned to EES (n=669) or PES (n=333) were analysed by an independent angiographic core laboratory. Side branch occlusion was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 or 1. Clinical outcomes through three years were compared by stent type and presence of side branch occlusion.. A total of 2,048 side branches were evaluated (EES N=1,345 side branches in 688 stented lesions, PES N=703 side branches in 346 stented lesions). Patients with compared to those without transient or final side branch occlusion had significantly higher non-Q-wave MI (NQMI) rates in-hospital (9.0% vs. 0.5%, p<0.0001). By multivariable analysis side branch occlusion was an independent predictor of NQMI (OR 4.45; 95% CI [1.82, 10.85]). Transient or final side branch occlusion occurred less frequently in patients receiving EES compared to PES (2.8% vs. 5.2%, p=0.009), contributing to the numerically lower rates of in-hospital NQMI with EES arm compared to PES (0.7% vs. 2.3%, p=0.05). Patients treated with EES rather than PES were less likely to develop side branch occlusion during stent placement, contributing to lower rates of periprocedural MI with EES compared to PES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome; United States

We compared the degree of systemic inflammation and its relation to the angiographic outcomes after drug-eluting stent (DES) implantations.. We implanted a single DES in 79 stable angina patients (50 men; 60.4 (9.5) years of age; sirolimus-eluting stent (SES), n = 38; paclitaxel-eluting stent (PES), n = 41). The high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were determined before and at 24 hours, 72 hours, and 4 weeks after the percutaneous coronary intervention (PCI). An angiography and intravascular ultrasound (IVUS) were performed.. The hs-CRP and IL-6 levels at baseline did not differ between the two groups. The hs-CRP increased significantly from baseline at 24 hours and 72 hours after the PCI in both groups and there was a significant increase in the IL-6 level at 24 hours after the PCI in both groups. However, there was no significant difference between the two groups in any of the hs-CRP or IL-6 measurements. At follow-up, the late lumen loss was significantly higher in the PES group than in the SES group (0.57 (0.56) mm vs 0.28 (0.58) mm, respectively, p = 0.020). The neointimal hyperplasia (NIH) volume in the PES group was significantly higher than that in the SES group (23.1 (22.7) vs 3.8 (7.1) mm(3), respectively, p = 0.000). The percentage luminal volume reduction was higher in the PES group than in the SES group (18.9 vs 3.9%, p = 0.002). The absolute values or change in the inflammatory markers did not correlate with the NIH or stent volume reduction.. Our study showed that the benefits obtained from the SES, which reduce neointimal proliferation, are not probably mediated by the attenuation of the systemic inflammatory markers hs-CRP or IL-6.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Inflammation Mediators; Interleukin-6; Male; Middle Aged; Paclitaxel; Prognosis; Prospective Studies; Sirolimus; Systemic Inflammatory Response Syndrome; Treatment Outcome; Tubulin Modulators; Ultrasonography

A comparison was made of sirolimus-eluting stents and bare stents as an effective means of treatment of stenosis in crural arteries. Patients were randomly divided into two groups: (1) patients treated with sirolimus-eluting stents and (2) patients treated with bare stents. Each group consisted of 25 patients, and every patient had one stent implanted. All patients showed symptoms of ischemia of the peripheral arteries, classified according to the Rutherford scale into categories 3, 4, and 5. All patients were examined 24 h before and 24 h and 6 months after the intervention. The results were analyzed according to clinical, hemodynamic, and angiographic criteria. Technically, the procedure was successful in 100% of cases, and both groups presented an equal improvement in clinical and hemodynamic parameters. The follow-up angiographic examination demonstrated a significantly lower rate of restenosis among the sirolimus-eluting stent group (4, 16%) versus the bare stent group (19, 76%) (p < 0.001), with lower target lesion revascularization in 3 (12%) versus 14 (56%) (p < 0.05), respectively. Quantitative angiography demonstrated that all variables used to assess restenosis were superior for sirolimus-eluting stents 6 months after intervention: late lumen loss 0.46 +/- 0.72 versus 1.70 +/- 0.94 (p < 0.001) and minimal lumen diameter 2.25 +/- 0.82 versus 0.99 +/- 1.08 (p < 0.001). Results of this study reveal that the use of sirolimus-eluting stents decreases the risk of restenosis in comparison to standard stents.

Topics: Aged; Aged, 80 and over; Angiography; Arteries; Atherosclerosis; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Ischemia; Male; Middle Aged; Sirolimus; Stents

To assess the efficacy of the AXXESS stent on the treatment of left main coronary artery (LMCA) bifurcation lesions using IVUS.. The treatment of LMCA bifurcation lesions remains challenging even with the use of drug-eluting stents. The AXXESS system is a biolimus A9-eluting self-expanding stent, dedicated to the treatment of bifurcation lesions.. Data were obtained from the AXXENT trial, a prospective, single-arm, multicenter study designed to evaluate the efficacy of the AXXESS stent on the treatment of LMCA bifurcation lesions. IVUS was available in 26 cases at 6-months follow-up. Volumetric and cross-sectional analyses within the AXXESS stent, and cross-sectional analyses at the ostia of left anterior descending (LAD) and left circumflex coronary arteries (LCX) were performed.. Within the AXXESS stent, percent neointimal volume obstruction was (3.0 +/- 4.1)% with a minimal lumen area of 10.3 +/- 2.6 mm(2). AXXESS stent volume showed an 12.4% increase at follow-up compared with postprocedure (P = 0.04). Lumen area was significantly smaller in the LCX ostium compared with the LAD ostium at follow-up (3.6 +/- 1.3 mm(2) vs. 5.5 +/- 2.0 mm(2), P = 0.0112). There was greater neointimal formation in the LCX ostium compared with the LAD ostium (1.37 +/- 1.20 mm(2) vs. 0.30 +/- 0.36 mm(2), P = 0.0003).. The AXXESS stent in the LMCA showed enlargement through 6-months follow-up and significant neointimal suppression. Greater neointimal formation and relatively inadequate stent expansion may contribute to luminal narrowing in the LCX ostium.

Topics: Aged; Alloys; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Europe; Female; Humans; Male; Middle Aged; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional; United States

Sirolimus-eluting stents have been reported to be effective in the treatment of coronary bifurcations. Still, it has not been fully clarified which strategy would provide the best results with true bifurcation lesions.. The CACTUS trial (Coronary bifurcations: Application of the Crushing Technique Using Sirolimus-eluting stents) is a prospective, randomized, multicenter study comparing 2 different techniques of stenting, with mandatory final kissing-balloon inflation, in true bifurcations: (1) elective "crush" stenting and (2) stenting of only the main branch, with provisional side-branch T-stenting. From August 2004 to June 2007, 350 patients were enrolled in 12 European centers. The primary angiographic end point was the in-segment restenosis rate, and the primary clinical end point was the occurrence of major adverse cardiac events (cardiac death, myocardial infarction, or target-vessel revascularization) at 6 months. At 6 months, angiographic restenosis rates were not different between the crush group (4.6% and 13.2% in the main branch and side branch, respectively) and the provisional stenting group (6.7% and 14.7% in the main branch and side branch, respectively; P=NS). Additional stenting on the side branch in the provisional stenting group was required in 31% of lesions. Rates of major adverse cardiac events were also similar in the 2 groups (15.8% in the crush group versus 15% in the provisional stenting group, P=NS).. In most bifurcations with a significant stenosis in both branches, a provisional strategy of stenting the main branch only is effective, with the need to implant a second stent on the side branch occurring in approximately one third of cases. The implantation of 2 stents does not appear to be associated with a higher incidence of adverse events at 6 months.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Treatment Outcome

The aim of the present study was to evaluate angiographic late luminal loss after the implantation of sirolimus-eluting Cypher stents and paclitaxel-eluting Taxus stents in patients with diabetes. The study was a Danish multicenter, open-label, randomized trial. One hundred fifty-three patients with diabetes with coronary artery disease were randomized to Cypher (n = 76) or Taxus (n = 77) stent implantation. All patients were followed for 8 months. The primary end point was 8-month angiographic in-stent late luminal loss. This primary end point was reduced in the Cypher group compared with the Taxus group (0.23 +/- 0.54 vs 0.44 +/- 0.52 mm, p = 0.025). Angiographic in-segment restenosis at 8-month follow-up, a secondary end point, was present in 16 patients (Cypher, n = 6; Taxus, n = 10; p = 0.24). Target lesion revascularization was performed in 5 patients (6.5%) and 9 patients (11.8%) in the Cypher and Taxus groups, respectively (p = 0.25). Definite stent thrombosis was observed in 2 patients (in the Taxus group), no patients had probable stent thrombosis, and 1 patient in each group had possible stent thrombosis. Major adverse cardiac events (cardiac death, myocardial infarction, definite stent thrombosis, or target lesion revascularization) were observed in 17 patients (Cypher, n = 6; Taxus, n = 11; p = 0.19). In conclusion, angiographic in-stent late luminal loss is significantly reduced in patients with diabetes by use of the sirolimus-eluting Cypher stent compared with the paclitaxel-eluting Taxus stent.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Sirolimus

In the prospective randomized Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) III trial, an everolimus-eluting stent (EES) compared with a widely used paclitaxel-eluting stent (PES) resulted in a statistically significant reduction in angiographic in-segment late loss at 8 months and noninferior rates of target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 1 year. The safety and efficacy of EES after 1 year have not been reported.. A total of 1002 patients with up to 2 de novo native coronary artery lesions (reference vessel diameter, 2.5 to 3.75 mm; lesion length < or =28 mm) were randomized 2:1 to EES versus PES. Antiplatelet therapy consisted of aspirin indefinitely and a thienopyridine for > or =6 months. Between 1 and 2 years, patients treated with EES compared with PES tended to have fewer episodes of protocol-defined stent thrombosis (0.2% versus 1.0%; P=0.10) and myocardial infarctions (0.5% versus 1.7%; P=0.12), with similar rates of cardiac death (0.3% versus 0.3%; P=1.0) and target vessel revascularization (2.9% versus 3.0%; P=1.0). As a result, at the completion of the 2-year follow-up, treatment with EES compared with PES resulted in a significant 32% reduction in target vessel failure (10.7% versus 15.4%; hazard ratio, 0.68; 95% confidence interval, 0.48 to 0.98; P=0.04) and a 45% reduction in major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization; 7.3% versus 12.8%; hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.83; P=0.004). Among the 360 patients who discontinued clopidogrel or ticlopidine after 6 months, stent thrombosis subsequently developed in 0.4% of EES patients versus 2.6% of PES patients (P=0.10).. Patients treated with EES rather than PES experienced significantly improved event-free survival at a 2-year follow-up in the SPIRIT III trial, with continued divergence of the hazard curves for target vessel failure and major adverse cardiac events between 1 and 2 years evident. The encouraging trends toward fewer stent thrombosis episodes after 6 months in EES-treated patients who discontinued a thienopyridine and after 1 year in all patients treated with EES rather than PES deserve further study.

Topics: Aged; Angioplasty; Antineoplastic Agents, Phytogenic; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Paclitaxel; Platelet Aggregation Inhibitors; Prospective Studies; Sirolimus; Treatment Outcome

Long-term polymer residue in the coronary milieu is a consequence of current drug-eluting stent (DES) therapy and has been implicated in late adverse events. We developed a novel polymer-free rapamycin- and probucol-eluting stent (Dual-DES) and compared its efficacy against commercially available permanent polymer-based sirolimus-eluting (SES; Cypher) and zotarolimus-eluting (ZES; Endeavor) stents.. Between March 2006 and July 2007, a total of 1007 patients undergoing coronary stenting of de novo lesions, in native vessels, were randomized to treatment with SES (n = 335), Dual-DES (n = 333), or ZES (n = 339). The primary endpoint was binary angiographic restenosis at 6-8 month follow-up angiography. Secondary endpoints were angiographic in-stent late loss; and target lesion revascularization (TLR), death/myocardial infarction and stent thrombosis at 12 months. Follow-up angiographic data were available for 828 (82.2%) patients. There was a significant difference in both binary restenosis and TLR across treatment groups (P = 0.003 and P < 0.001, respectively). Binary restenosis in the Dual-DES group (11.0%) was significantly lower than that in the ZES group (19.3%; P = 0.002) but comparable with that in the SES group (12.0%; P = 0.68). Similarly, TLR with Dual-DES (6.8%) was significantly lower than ZES (13.6%; P = 0.001) but not different to that of SES (7.2%; P = 0.83). These differences were mirrored in the extent of late loss across the groups. No differences were observed between stent groups in terms of death/myocardial infarction or stent thrombosis.. A novel polymer-free Dual-DES is associated with high anti-restenotic efficacy without recourse to carrier polymer. Potential long-term clinical advantage of this platform remains subject to investigation. Study registered at ClinicalTrials.gov. Identifier number: NCT00332397.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Disease-Free Survival; Drug-Eluting Stents; Female; Humans; Male; Myocardial Infarction; Myocardial Revascularization; Polymers; Probucol; Prospective Studies; Sirolimus; Treatment Outcome; Tubulin Modulators

Topics: Antineoplastic Agents, Phytogenic; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Paclitaxel; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Patients with diabetes have an increased risk of in-stent restenosis after coronary stent implantation. Serial intravascular ultrasound was used to study chronic arterial responses and edge effects after implantation of Cypher (Cordis, Johnson & Johnson, Miami Lakes, Florida) or Taxus (Boston Scientific, Maple Grove, Minnesota) stents in diabetic patients. Seventy-four diabetic patients were randomly assigned to Cypher or Taxus stent implantation. Intravascular ultrasound of 5-mm long segments immediately proximal and distal to the stent was performed after the procedure and at the 8-month follow-up. The increase in peri-stent external elastic membrane (EEM) volume was more pronounced in the Taxus group (292.4 +/- 132.6 to 309.5 +/- 146.8 mm(3)) than in the Cypher group (274.4 +/- 137.2 to 275.4 +/- 140.1 mm(3); p = 0.005). Peri-stent plaque volume increased in the Taxus group (152.5 +/- 73.7 to 166.1 +/- 85.1 mm(3)), but was unchanged in the Cypher group (153.5 +/- 75.5 to 151.5 +/- 75.8 mm(3); p = 0.002). In proximal and distal reference segments, mean lumen area decreased within the entire 5-mm edge segment (proximal and distal) because of plaque progression (distal, 5.5 +/- 3.6 to 5.8 +/- 3.7 mm(2); p = 0.097; proximal, 8.1 +/- 2.7 to 8.7 +/- 2.9 mm(2); p = 0.006) without remodeling (change in EEM) in the Taxus group. Conversely, there were no significant changes in reference-segment EEM or plaque areas in the Cypher group. In conclusion, in diabetic patients, Taxus stent implantation was associated with increased (1) peri-stent EEM volume and peri-stent plaque, and (2) stent edge plaque progression accompanied by lumen reduction without remodeling. These findings were not seen in Cypher stents.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Ultrasonography, Interventional

The everolimus-eluting stent (EES) is a newly developed drug-eluting stent using the MULTILINK VISION stent platform combined with the drug everolimus contained in a polymer coating. Recently reported randomized trials have shown the noninferiority and subsequent superiority of the EES compared with the paclitaxel-eluting stent regarding in-stent late loss (LL) at 180 days. However, there have been no studies comparing head to head the EES with the sirolimus-eluting stent (SES), which has shown the least amount of LL among the previously released drug-eluting stent (DES). In addition, adjunctive antiplatelet therapy is a critical factor in optimizing long-term DES safety. Despite the recommendation of the American Heart Association/American College of Cardiology to maintain 12 months of dual antiplatelet therapy, there have been no prospective randomized trials comparing the efficacy and safety of different durations.. In the Efficacy of Xience/promus versus Cypher in rEducing Late Loss after stENTing (EXCELLENT) trial, approximately 1,400 patients are being prospectively and randomly assigned in a 2 x 2 factorial design according to the type of stent (EES vs SES) and the duration of dual antiplatelet therapy (6 vs 12 months). The primary end point is in-segment LL at 9 months for comparison of type of stent, and the coprimary end point is target vessel failure at 12 months for comparison of dual antiplatelet therapy duration.. The EXCELLENT trial is the largest study yet performed to directly compare the efficacy and safety of the EES versus the SES. In addition, this study will also address the issue of a 6- versus 12-month duration of dual antiplatelet therapy for post-percutaneous coronary intervention management.

Topics: Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Incidence; Korea; Male; Myocardial Revascularization; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

Angiographic parameters (such as late luminal loss) are common endpoints in drug-eluting stent trials, but their correlation with the neointimal process and their reliability in predicting restenosis are debated.. Using quantitative coronary angiography (QCA) data (49 bare metal stent and 44 sirolimus-eluting stent lesions) and intravascular ultrasound (IVUS) data (39 bare metal stent and 34 sirolimus-eluting stent lesions) from the randomised Reduction of Restenosis In Saphenous vein grafts with Cypher stent (RRISC) trial, we analysed the "relocation phenomenon" of QCA-based in-stent minimal luminal diameter (MLD) between post-procedure and follow-up and we correlated QCA-based and IVUS-based restenotic parameters in stented saphenous vein grafts. We expected the presence of MLD relocation for low late loss values, as MLD can "migrate" along the stent if minimal re-narrowing occurs, while we anticipated follow-up MLD to be located close to post-procedural MLD position for higher late loss. QCA-based MLD relocation occurred frequently: the site of MLD shifted from post-procedure to follow-up an "absolute" distance of 5.8 mm [2.5-10.2] and a "relative" value of 29% [10-46]. MLD relocation failed to correlate with in-stent late loss (rho = 0.14 for "absolute" MLD relocation [p = 0.17], and rho=0.03 for "relative" relocation [p = 0.811). Follow-up QCA-based and IVUS-based MLD values well correlated in the overall population (rho = 0.76, p < 0.001), but QCA underestimated MLD on average 0.55 +/- 0.49 mm, and this was mainly evident for lower MLD values. Conversely, the location of QCA-based MLD failed to correlate with the location of IVUS-based MLD (rho = 0.01 for "absolute" values--in mm [p = 0.911, rho = 0.19 for "relative" values--in % [p = 0.111). Overall, the ability of late loss to "predict" IVUS parameters of restenosis (maximum neointimal hyperplasia diameter, neointimal hyperplasia index and maximum neointimal hyperplasia area) was moderate (rho between 0.46 and 0.54 for the 3 IVUS parameters).. These findings suggest the need for a critical re-evaluation of angiographic parameters (such as late loss) as endpoints for drug-eluting stent trials and the use of more precise techniques to describe accurately and properly the restenotic process.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Double-Blind Method; Drug-Eluting Stents; Graft Occlusion, Vascular; Humans; Metals; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Saphenous Vein; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Patency

The aim of this study was to examine the 5-year clinical safety and efficacy outcomes in patients enrolled in the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) trial.. The SIRIUS trial was a double-blinded randomized study that demonstrated that sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS).. Patients (n = 1,058) with de novo native coronary artery lesions were randomized to either SES (n = 533) or control BMS (n = 525) and were followed for 5 years.. Between 1 and 5 years, additional clinical events were similarly distributed among the sirolimus and control groups. At 5 years, in sirolimus versus control patients, target lesion revascularization was 9.4% versus 24.2% (p < 0.001) and major adverse cardiovascular events and target vessel failure rates were 20.3% versus 33.5% and 22.5% versus 33.5%, respectively (p < 0.0001 for both). There were no significant differences in death, myocardial infarction, and nontarget lesion revascularization. No significant differences were observed in the cumulative incidence of stent thrombosis for sirolimus versus control patients with either protocol-derived (1.0% vs. 0.8%) or Academic Research Consortium definitions (3.9% vs. 4.2%).. In patients with noncomplex coronary artery disease, clinical outcomes 5 years after implantation of SES continue to demonstrate significant reduction in the need for repeat revascularization, with similar safety (death and myocardial infarction) compared with BMS, without evidence for either disproportionate late restenosis or late stent thrombosis.

Topics: Adult; Aged; Aged, 80 and over; Confidence Intervals; Coronary Restenosis; Double-Blind Method; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors; Sirolimus; Survivors; Time Factors

We prospectively compared coronary endothelial dysfunction in patients with zotarolimus-eluting stent (ZES) versus sirolimus-eluting stent (SES) implantation at 6-month follow-up.. A ZES has been associated with uniform and rapid healing of the endothelium.. Fifty patients were randomly treated with intravascular ultrasound-guided stenting with a single stent to the mid-segment of the left anterior descending artery (20 ZES, 20 SES, and 10 bare-metal stents), and endothelial function was estimated before and after intervention at 6-month follow-up by incremental acetylcholine (Ach) (10, 20, 50, and 100 microg/min) and nitrate (200 microg/min) infusions into the left coronary ostium. The vascular response was quantitatively measured in the 5-mm segments proximal and distal to the stent.. In the drug-eluting stent groups, more intense vasoconstriction to incremental doses of Ach was observed at 6-month follow-up compared with the responses before stenting. Endothelial function associated with the ZES was more preserved at 6-month follow-up compared with the SES. Vasoconstriction to Ach was more prominent in the distal segments than the proximal segments in both the ZES and SES groups. Endothelium-independent vasodilation to nitrate did not differ significantly among the study groups.. Vasoconstriction in response to Ach in the peri-stent region was less pronounced in the ZES group than the SES group at 6-month follow-up, which suggests that endothelial function associated with ZES can be more preserved than the SES.

Topics: Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; ROC Curve; Sirolimus; Time Factors; Vasoconstriction

The aim of this trial was to compare the safety and efficacy of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) for treatment of unprotected left main coronary artery (uLMCA) disease.. Both PES and SES have reduced the risk of restenosis, particularly in high-risk patient and lesion subsets. However, their comparative performance in uLMCA lesions is not known.. In this randomized study, 607 patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention for uLMCA were enrolled: 302 were assigned to receive a PES (Taxus, Boston Scientific, Natick, Massachusetts) and 305 assigned to receive a SES (Cypher, Cordis, Johnson & Johnson, New Brunswick, New Jersey). The primary end point was the combined incidence of death, myocardial infarction, and target lesion revascularization (TLR) at 1 year. The secondary end point was angiographic restenosis on the basis of the LMCA area analysis at follow-up angiography.. At 1 year the cumulative incidence of death, myocardial infarction, or TLR was 13.6% in the PES and 15.8% in the SES group (relative risk [RR]: 0.85, 95% confidence interval [CI]: 0.56 to 1.29, p = 0.44). One patient in the PES group (0.3%) and 2 patients in the SES group (0.7%) experienced definite stent thrombosis (p = 0.57). Mortality at 2 years was 10.7% in the PES and 8.7% in the SES group (RR: 1.14, 95% CI: 0.66 to 1.95, p = 0.64). Angiographic restenosis was 16.0% with PES and 19.4% with SES (RR: 0.82, 95% CI: 0.57 to 1.19, p = 0.30).. Implantation of either PES or SES in uLMCA lesions is safe and effective; both of these drug-eluting stents provide comparable clinical and angiographic outcomes. (Drug-Eluting-Stents for Unprotected Left Main Stem Disease [ISAR-LEFT-MAIN]; NCT00133237).

Topics: Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Confidence Intervals; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Incidence; Male; Myocardial Infarction; Paclitaxel; Platelet Aggregation Inhibitors; Risk; Sirolimus; Ticlopidine; Tubulin Modulators

This study sought to evaluate the safety and efficacy of a biodegradable polymer-coated sirolimus-eluting stent (Excel, JW Medical System, Weihai, China) with 6-month dual antiplatelet therapy in daily practice.. It has been hypothesized that persistent presence of polymer may compromise the safety of drug-eluting stents, and that therefore biodegradable polymer coatings might reduce late adverse events.. Between June and November 2006, 2,077 patients, exclusively treated with Excel stents at 59 centers from 4 countries, were enrolled in this prospective, multicenter registry. Recommended antiplatelet regimen included clopidogrel and aspirin for 6 months followed by chronic aspirin therapy.. The average duration of clopidogrel treatment was 199.8 +/- 52.7 days and 80.5% of discharged patients discontinued clopidogrel at 6 months. The cumulative rates of major adverse cardiac events were 0.9% at 30 days, 2.7% at 1 year, and 3.1% at 18 months. Overall rate of stent thrombosis was 0.87% at 18 months. The rates of acute, subacute, late, and very late stent thrombosis were 0.1%, 0.38%, 0.34%, and 0.05%, respectively. Angiographic follow-up, performed in 974 (31.6%) lesions from 653 patients (31.7%), revealed a mean in-stent late lumen loss of 0.21 +/- 0.39 mm. Binary restenosis rates were 3.8% in-stent and 6.7% in-segment.. This multicenter registry documents satisfactory safety and efficacy profiles, as evidenced by low rates of major adverse cardiac events and stent thrombosis up to 18 months, for the Excel biodegradable polymer-based sirolimus-eluting stent when used with 6 months of dual antiplatelet therapy in a "real-world" setting. (Multi-Center Registry Trial of EXCEL Biodegradable Polymer Drug-Eluting Stent [CREATE]; NCT00331578).

Topics: Aged; Angioplasty, Balloon, Coronary; Asia; Aspirin; Cardiovascular Agents; Clopidogrel; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Polymers; Product Surveillance, Postmarketing; Prospective Studies; Prosthesis Design; Registries; Risk Assessment; Sirolimus; Thrombosis; Ticlopidine; Time Factors; Treatment Outcome

We used optical coherence tomography, which has a resolution of <20 microm, to analyze thin layers of neointima in rapamycin-eluting coronary stents.. Lack of neointimal coverage has been implicated in the pathogenesis of drug-eluting coronary stent thrombosis. Angiography and intracoronary ultrasound lack the resolution to examine this.. We conducted a randomized trial in patients receiving polymer-coated rapamycin-eluting stents (Cypher, Cordis, Johnson & Johnson, Miami, Florida) and nonpolymer rapamycin-eluting stents (Yukon, Translumina, Hechingen, Germany) to examine neointimal thickness, stent strut coverage, and protrusion at 90 days. Twenty-four patients (n = 12 for each group) underwent stent deployment and invasive follow-up at 90 days with optical coherence tomography. The primary end point was binary stent strut coverage. Coprimary end points were neointimal thickness and stent strut luminal protrusion.. No patient had angiographic restenosis. For polymer-coated and nonpolymer rapamycin-eluting stents, respectively, mean (SD), neointimal thickness was 77.2 (25.6) microm versus 191.2 (86.7) mum (p < 0.001). Binary stent strut coverage was 88.3% (11.8) versus 97.2% (6.1) (p = 0.030). Binary stent strut protrusion was 26.5% (17.5) versus 4.8% (8.6) (p = 0.001).. Mean neointimal thickness for the polymer-coated rapamycin-eluting stent was significantly less than the nonpolymer rapamycin-eluting stent but as a result coverage was not homogenous, with >10% of struts being uncovered. High-resolution imaging allowed development of the concept of the protrusion index, and >25% of struts protruded into the vessel lumen with the polymer-coated rapamycin-eluting stent compared with <5% with the nonpolymer rapamycin-eluting stent. These findings may have important implications for the risk of stent thrombosis and, therefore, future stent design. (An optical coherence tomography study to determine stent coverage in polymer coated versus bare metal rapamycin eluting stents. ORCA 1, from the Optimal Revascularization of the Coronary Arteries group; ISRCTN42475919).

Topics: Confidence Intervals; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Polymers; Sirolimus; Tomography, Optical Coherence

It has been demonstrated that, in comparison with bare-metal stents (BMS), sirolimus-eluting stents (SES) reduce restenosis after the percutaneous revascularization of small coronary arteries, but the long-term clinical outcomes of this treatment have not yet been investigated.. The long-term SES-SMART clinical study was a multicentre, prospective, randomized, single-blind study of 257 patients receiving a SES or BMS in a small coronary artery, who were evaluated at discharge, 30 days, 8 and 24 months after stenting. The clinical endpoint of the study was a 24 months composite of major adverse cardiac and cerebrovascular events, which included death, non-fatal myocardial infarction, ischaemia-driven target lesion revascularization (TLR), and cerebrovascular accident. The 24 months follow-up was completed by 254 patients (98.8%). The use of SES was associated with a significantly lower incidence of the clinical endpoint (12.6% vs. 33.1%; HR 0.30, 95% CI: 0.17-0.55; P < 0.0001), which was not only due to a reduction in TLR (7.9% vs. 29.9%; HR 0.30, 95% CI: 0.16-0.59; P < 0.0001), but also to a reduction in myocardial infarction (1.6% vs. 10.2%; HR 0.09, 95% CI: 0.01-0.66; P = 0.018).. In comparison with BMS, the use of SES in the percutaneous revascularization of small coronary arteries is associated with improved clinical outcomes after 2 years follow-up.

Topics: Aged; Cerebrovascular Disorders; Coronary Restenosis; Death, Sudden, Cardiac; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Prospective Studies; Risk Factors; Single-Blind Method; Sirolimus; Treatment Outcome; Tubulin Modulators

Stent length is a major predictor of restenosis in stable patients undergoing percutaneous coronary intervention (PCI) with bare metal stents (BMS). The effect of stent length is decreased by using drug eluting stents, however, this association had not been previously determined in patients with acute myocardial infarction (AMI). We sought to determine the impact of stent length on restenosis in patients who undergo primary PCI for AMI.. Three-hundred and fifty-seven and 355 patients with AMI were included respectively in the BMS and SES (sirolimus eluting stents) arms of the Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated with Balloon Angioplasty (TYPHOON). Patients were divided into four subgroups based on the total length of the culprit lesion stented segment (in mm) : <18, >or=18 and <23, >or=23 and < 28, and >or=28 (groups 1 - 4 respectively). Target lesion revascularisation (TLR) and angiographic late loss were used to assess the restenotic process. Despite similar lesion length, average stent length was longer in patients treated with SES as compared to BMS 22.1+/-8.6 and 20.3+/-8.2 mm respectively, p=0.005. The rate of 12m death and AMI was similar in SES and BMS. There was no significance influence of stent length on % TLR neither in BMS (12.6, 10.1, 17.4 and 12.3 - subgroups 1-4 respectively) nor in SES (3.9, 5, 2.2 and 2.7 respectively). There was also no significant impact of stent length on angiographic late loss (mm) neither in BMS (0.7, 0.87, 0.84 and 0.92 respectively) nor in SES (0.32, 0.0, 0.11 and 0.3 respectively).. Physicians tend to choose longer SES than BMS for a similar lesion length during primary PCI for AMI. Interestingly, stent length did not affect clinical or angiographic restenosis neither in BMS nor in SES in this group of patients who underwent primary PCI for acute MI. This data challenges current practice concerning the chosen stent length in patients with AMI.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Europe; Female; Humans; Israel; Male; Metals; Middle Aged; Myocardial Infarction; Prosthesis Design; Risk Assessment; Risk Factors; Severity of Illness Index; Single-Blind Method; Sirolimus; Stents; Time Factors; Treatment Outcome

We evaluated the role of gender on clinical and angiographic results of the everolimus-eluting stent in the SPIRIT III trial.. The SPIRIT III trial demonstrated superior efficacy of the XIENCE V everolimus-eluting stent compared with the TAXUS paclitaxel-eluting stent. Whether these results are applicable to women is unknown.. A total of 1,002 patients with coronary artery lesions of 28 mm or less long in 2.5-3.75 mm diameter vessels were prospectively randomized to receive percutaneous coronary intervention with either XIENCE V stent or TAXUS stent placement. Post hoc gender subset analysis was performed.. A total of 669 patients (200 women) received the XIENCE V stent, and 332 patients (114 women) were assigned to the TAXUS stent. Women were older and had more hypertension and diabetes than men. At 1 year, rates of MACE (11.1% vs. 5.7%, P = 0.004), TVF (13.7% vs. 7.5%, P = 0.003), TVR (10.8% vs. 4.6%, P = 0.0007), and TLR (7.2% vs. 2.7%, P = 0.002) were higher in women compared with men. The difference in 1 year MACE and TVF rates between men and women remained after adjusting for baseline covariates. Although the angiographic characteristics at baseline were similar among the female cohort, women assigned to XIENCE V had lower in-stent late loss (0.19 vs. 0.42 mm, P = 0.01) compared with women treated with the TAXUS stent. Although 30-day clinical outcomes were similar for women treated with XIENCE V and TAXUS stents, at 1 year, women with XIENCE V stents had significantly lower MACE (8.2% vs. 16.1 %, P = 0.04) and TVR (3.1% vs. 8.9%, P = 0.03) compared with those treated with TAXUS stents. Stent thrombosis rates were similar between women receiving either XIENCE V or TAXUS stents.. Women in the SPIRIT III trial had inherently higher MACE and TVF rates than men. However, the angiographic and clinical benefits of using XIENCE V stents are generalizable to women.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Linear Models; Logistic Models; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sex Factors; Single-Blind Method; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Women's Health

To study long-term results of 3-42-month (mean 18.1 +/- 1.2 month) of a prospective clinically and angiologically controlled follow-up after coronary endovascular revascularisation with sirolimus-eluting stents (SES) in patients with coronary heart disease (CHD) comorbid with type 2 diabetes mellitus (DM).. A total of 108 CHD patients with angina pectoris resistant to antianginal therapy were divided into 2 groups: 51 CHD patients with mild and moderate type-2 DM (group 1); 57 CHD patients free of diabetes (group 2). All the patients have undergone successful coronary endovascular revascularisation with SES. Anti-ischemic efficacy and safety of stenting were studied in the course of 18-month prospective follow-up.. An anti-ischemic effect of stenting in hospital setting was achieved in all the patients. 18 months after stenting frequency and severity of anginal attacks reduced in group 1 by 70.6%, daily need in nitroglycerine--by 71.9%, in group 2--by 87.1 and 93.1%, respectively. As a result, exercise tolerance improved in group 1 by 38.3%, in group 2--by 40.8%. Quality of life improved by 22.7 and 25.1%, respectively. Most of the patients showed no deterioration of carbohydrate and lipid metabolism compensation. Recurrent angina and symptoms of painless myocardial ischemia occurred in 39.3 and 14% patients of group 1 and 2, respectively. More frequent causes of the recurrence were progression of coronary artery atherosclerosis de novo and Cypher stent restenosis (11.8 and 3.5% in group 1 and 2, respectively).. SES implantation provided good anti-ischemic efficacy in 60.7 and 86% CHD patients with and without DM, respectively. It significantly improved exercise tolerance and quality of life.

Topics: Coronary Angiography; Coronary Restenosis; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Prospective Studies; Quality of Life; Sirolimus; Time Factors; Treatment Outcome

We sought to compare patient-oriented outcomes related to target vessel or nontarget vessel events for sirolimus-eluting stents (SES) versus bare-metal stents.. SES significantly reduce restenosis but the influence of reduced restenosis on overall patient-oriented outcome has not been reported.. The study population included 1,057 patients randomized in the SIRIUS (Sirolimus-Eluting Stent in De Novo Native Coronary Lesions) study and followed clinically for 5 years. The primary end point was a composite of all-cause mortality, any myocardial infarction, or any repeat revascularization. In secondary analyses, myocardial infarction and repeat revascularization events attributed to the target vessel or a nontarget vessel were compared by stent type.. Patients with an SES were more likely to be free from the primary composite end point at 5 years (60.4% vs. 47.8%, p < 0.001) chiefly due to a sustained reduction in target lesion revascularization for SES (cumulative incidence: 12.5% vs. 28.8%, p < 0.001). There was no difference in the cumulative incidence of myocardial infarction or revascularization attributed to remote segments of the target vessel. Events attributed to the nontarget vessel were frequent and not different for SES versus bare-metal stents (25.7% vs. 25.8%).. The benefit of SES over bare-metal stents for reduced target lesion revascularization is maintained for 5 years. Remote coronary segments of the target vessel and nontarget vessel remain an important cause of future adverse events despite sustained restenosis benefit.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Disease Progression; Double-Blind Method; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome

Drug-eluting stent (DES) platforms devoid of durable polymer have potential to enhance long-term safety outcomes. The ISAR-TEST-3 study was a randomised trial comparing three rapamycin-eluting stents with different coating strategies. The present study examined 2-year outcomes of these patients and is the first large-scale trial to report longer-term outcomes with biodegradable polymer and polymer-free DES.. Patients with de novo coronary lesions in native vessels were randomly assigned to receive biodegradable polymer (BP; n = 202), permanent polymer (PP; Cypher; n = 202) and polymer-free (PF; n = 201) stents. The 2-year endpoints of interest were target lesion revascularisation (TLR), death/myocardial infarction (MI), stent thrombosis and delayed angiographic late luminal loss (LLL) between 6-8 months and 2 years.. There were no significant differences in TLR (8.4%, 10.4% and 13.4% for BP, PP and PF stents, respectively; p = 0.19), death/MI (5.9%, 6.4% and 6.5% with BP, PP and PF respectively; p = 0.97) or stent thrombosis (definite/probable 0.5%, 1.0% and 1.0% with BP, PP and PF, respectively; p = 0.82). Paired angiographic follow-up at 6-8 months and 2 years was available for 302 patients (69.0% of eligible patients). Delayed LLL was significantly different across the treatment groups: 0.17 (0.42) mm, 0.16 (0.41) mm and -0.01 (0.36) mm for BP, PP and PF stents, respectively (p<0.001).. Clinical antirestenotic efficacy was maintained with all three platforms between 1 and 2 years, although angiographic surveillance showed ongoing delayed LLL with both BP and PP stent platforms. At 2 years there was no signal of a differential safety profile between the three stent platforms.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Sirolimus; Treatment Outcome; Tubulin Modulators

We tested two novel drug-eluting stents (DES), covered with a biodegradable-polymer carrier and releasing paclitaxel or sirolimus, which were compared against a bare metal stent (primary objective). The DES differed by the drug, but were identical otherwise, allowing to compare the anti-restenosis effects of sirolimus versus paclitaxel (secondary objective).. The efficacy of novel DES with biodegradable polymers should be tested in the context of randomized trials, even when using drugs known to be effective, such as sirolimus and paclitaxel.. Overall, 274 patients with de novo coronary lesions in native vessels scheduled for stent implantation were randomly assigned (2:2:1 ratio) for the paclitaxel (n = 111), sirolimus (n = 106), or bare metal stent (n = 57) groups. Angiographic follow-up was obtained at 9 months and major cardiac adverse events up to 12 months.. Both paclitaxel and sirolimus stents reduced the 9-month in-stent late loss (0.54-0.44 mm, 0.32-0.43 mm, vs. 0.90-0.45 mm respectively), and 1-year risk of target vessel revascularization and combined major adverse cardiac events (P < 0.05 for both, in all comparisons), compared with controls. Sirolimus stents had lower late loss than paclitaxel stents (P < 0.01), but similar 1-year clinical outcomes. There were no differences in the risk of death, infarction, or stent thrombosis among the study groups.. Both novel DES were effective in reducing neointimal hyperplasia and 1-year re-intervention, compared to bare metal stents. Our findings also suggest that sirolimus is more effective than paclitaxel in reducing angiographic neointima, although this effect was not associated with better clinical outcomes.

Topics: Aged; Angioplasty, Balloon, Coronary; Brazil; Cardiovascular Agents; Cardiovascular Diseases; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Hyperplasia; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Paclitaxel; Proportional Hazards Models; Prosthesis Design; Risk Assessment; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome

The aim of this study was to compare the vessel response between zotarolimus-eluting stents (ZES) and paclitaxel-eluting stents (PES) using intravascular ultrasound.. The ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients With Coronary Artery Disease) trial was a randomized controlled study of zotarolimus-eluting, phosphorylcholine-coated, cobalt-alloy stents for the treatment of de novo coronary lesions compared with using PES for the same treatment.. Data were obtained from patients with serial (baseline and 8-months follow-up) intravascular ultrasound analysis available (n = 198). Volumetric analysis was performed for vessel, lumen, plaque, stent, and neointima. Cross-sectional narrowing (given as percentage) was defined as neointimal area divided by stent area. Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. Subsegment analysis was performed at every matched 1-mm subsegment throughout the stent.. At follow-up, the ZES group showed significantly greater percentage of neointimal obstruction (16.6 +/- 12.0% vs. 9.9 +/- 8.9%, p < 0.01) and maximum cross-sectional narrowing (31.8 +/- 16.1% vs. 25.2 +/- 14.9%, p < 0.01) with smaller minimum lumen area than the PES group did. However, the incidence of maximum cross-sectional narrowing >50% was similar in the 2 groups. Neointima-free frame ratio was significantly lower in the ZES group. In overall analysis, whereas the PES group showed positive remodeling during follow-up (13.7 +/- 4.2 mm(3)/mm to 14.3 +/- 4.3 mm(3)/mm), the ZES group showed no significant difference (12.7 +/- 3.6 mm(3)/mm to 12.9 +/- 3.5 mm(3)/mm). In subsegment analysis, significant focal positive vessel remodeling was observed in 5% of ZES and 25% of PES cases (p < 0.05).. There were different global and focal vessel responses for ZES and PES. Both drug-eluting stents showed a similar incidence of lesions with severe narrowing despite ZES having a moderate increase in neointimal hyperplasia compared with neointimal hyperplasia in PES. There was a relatively lower neointima-free frame ratio in ZES, suggesting a greater extent of neointimal coverage. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent System in Coronary Artery Lesions; NCT00217269).

Topics: Aged; Alloys; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coated Materials, Biocompatible; Cobalt; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Hyperplasia; Male; Middle Aged; Paclitaxel; Phosphorylcholine; Prosthesis Design; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional; United States

Although biodegradable polymer drug-eluting stent (DES) platforms have potential to enhance long-term clinical outcomes, data concerning their efficacy are limited to date. We previously demonstrated angiographic antirestenotic efficacy with a microporous, biodegradable polymer DES. In the current study, we hypothesized that at 12 months, its clinical safety and efficacy would be non-inferior to that of permanent polymer DES.. This prospective, randomized, open-label, active-controlled trial was conducted at two tertiary referral cardiology centres in Munich, Germany. Patients presenting with stable coronary disease or acute coronary syndromes undergoing DES implantation in de novo native-vessel coronary lesions were randomly assigned to treatment with biodegradable polymer DES (rapamycin-eluting; n = 1299) or permanent polymer DES (n = 1304: rapamycin-eluting, Cypher, n = 652; or everolimus-eluting, Xience, n = 652) and underwent clinical follow-up to 1 year. The primary endpoint was a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or revascularization related to the target lesion (TLR). Biodegradable polymer DES was non-inferior to permanent polymer DES concerning the primary endpoint [13.8 vs. 14.4%, respectively, P(non-inferiority) 0.005; relative risk = 0.96 (95% confidence interval, 0.78-1.17), P(superiority) = 0.66]. Biodegradable polymer DES in comparison with permanent polymer DES showed similar rates of cardiac death or MI related to the target vessel (6.3 vs. 6.2%, P = 0.94), TLR (8.8 vs. 9.4%, P = 0.58), and stent thrombosis (definite/probable: 1.0 vs. 1.5%, P = 0.29). Subgroup analysis of the biodegradable polymer DES vs. individual Cypher and Xience stent arms revealed no signal of performance difference.. A biodegradable polymer rapamycin-eluting stent is non-inferior to permanent polymer-based DES in terms of clinical efficacy over 1 year. These results provide a framework for testing the potential clinical advantage of biodegradable polymer DES over the medium to long term. The trial was registered at ClinicalTrials.gov (identifier: NCT00598676).

Topics: Absorbable Implants; Adult; Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Sirolimus; Treatment Outcome; Tubulin Modulators; Young Adult

Lesion length remains a predictor of target lesion revascularisation and results of long lesion stenting remain poor. Sirolimus-eluting stents have been shown to perform better than paclitaxel eluting stents in long lesions. In this substudy of the LEADERS trial, we compared the performance of biolimus biodegradable polymer (BES) and sirolimus permanent polymer stents (SES) in long lesions.. A total of 1,707 'all-comer' patients were randomly allocated to treatment with BES and SES. A stratified analysis of angiographic and clinical outcomes at nine months and one year, respectively was performed for vessels with lesion length <20 mm versus >20 mm (as measured by quantitative angiography).Of 1,707 patients, 592 BES patients with 831 lesions and 619 SES patients with 876 lesions had only short lesions treated. One hundred and fifty-three BES patients with 166 lesions and 151 SES patients with 162 lesions had long lesions. There were no significant differences in baseline clinical characteristics, except for higher number of patients with long lesions presenting with acute myocardial infarction in both stent groups. Long lesions tended to have lower MLD and greater percent diameter stenosis at baseline than short lesions. Late loss was greater for long lesions than short lesions. There was no statistically significant difference in late loss between BES and SES stents (0.32+/-0.69 vs 0.24+/-0.57, p=0.59). Binary in-segment restenosis was present in 23.2% versus 13.1% of long lesions treated with BES and SES, respectively (p=0.042). In patients with long lesions, the overall MACE rate was similar for BES and SES (17% vs 14.6%; p=0.62). There was a trend towards higher overall TLR rate with BES (12.4 % vs 6.0%; HR=2.06; p=0.07) and clinically driven TLR (10.5% vs 5.3%: HR 1.94; p=0.13). Rates of definite stent thrombosis were 3.3% in the long lesion group and 1.3-1.7 % in the short lesion group.. BES and SES appear similar with respect to MACE in long lesions in this "all-comer" patient population. However, long lesions tended to have a higher rate of binary in-segment restenosis and TLR following BES than SES treatment.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Europe; Female; Humans; Male; Middle Aged; Myocardial Infarction; Polymers; Proportional Hazards Models; Prosthesis Design; Risk Assessment; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

We assessed the impact of vessel size on outcomes of stenting with biolimus-eluting degradable polymer stent (BES) and sirolimus-eluting permanent polymer stent (SES) within a randomized multicenter trial (LEADERS).. Stenting of small vessels might be associated with higher rates of adverse events.. "All-comer" patients (n = 1,707) were randomized to BES and SES. Post-hoc-stratified analysis of angiographic and clinical outcomes at 9 months and 1 year, respectively, was performed for vessels with reference diameter 2.75 mm.. Of 1,707 patients, 429 patients in the BES group with 576 lesions and 434 patients in the SES group with 557 lesions had only small vessels treated (50.6% of the patient cohort). In patients with small vessels there was no significant difference in overall major adverse cardiac events (MACE) rate (12.1% vs. 11.8%; p = 0.89) or target lesion revascularization (TLR) rate (9.6% vs. 7.4%; p = 0.26) between BES and SES. The MACE and TLR rates in the small-vessel patient population were higher than in the large-vessel population. The TLR rate was 9.6% versus 2.6%, and MACE rate was 12.1% versus 7.1% for small versus large vessels in the BES arm (TLR: hazard ratio [HR] = 3.724, p = 0.0013; MACE: HR = 1.720, p = 0.0412). In the SES arm, TLR was 7.4% versus 5.1%, and MACE was 11.8% versus 10.3% in small versus large vessels (TLR: HR = 1.435, p = 0.2594; MACE: HR = 1.149, p = 0.5546).. Prevalence of small vessel disease is high in an "all-comer" population with higher TLR and MACE rates. The BES and SES seem equivalent in treatment outcomes of small vessels in this "all-comer" patient population.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Europe; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Polymers; Proportional Hazards Models; Prosthesis Design; Risk Assessment; Severity of Illness Index; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

The aim of this study was to examine outcomes related to the use of the Endeavor zotarolimus-eluting stent (ZES) (Medtronic CardioVascular, Santa Rosa, California) compared with the TAXUS paclitaxel-eluting stent (PES) (Boston Scientific Corp., Natick, Massachusetts) in the 477 patients with diabetes mellitus (DM) enrolled in the randomized ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) trial.. Percutaneous coronary intervention (PCI) in diabetic patients is associated with increased rates of restenosis-related end points compared with PCI in nondiabetic patients. Although ZES has been associated with similar clinical efficacy compared with PES in the overall trial population of the ENDEAVOR IV trial, whether these results are maintained in the higher-risk restenosis subgroup of patients with DM has not been determined.. Clinical and angiographic outcomes were compared according to randomized treatment assignment to either ZES or PES.. Baseline characteristics were similar among ZES (n = 241) and PES (n = 236) diabetic patients, with slightly longer lesion lengths in PES-treated patients (12.9 mm vs. 14.0 mm, p = 0.041). Among the 86 DM patients assigned to routine angiographic follow-up (18% of the overall DM cohort), in-stent percent diameter stenosis at 8 months was greater among ZES-treated patients (32.9 vs. 21.1, p = 0.023), with a trend toward higher in-stent late loss. One-year clinical outcomes were similar among DM patients treated with either ZES or PES (target vessel failure: 8.6% vs. 10.8%, p = 0.53; target lesion revascularization: 6.9% vs. 5.8%, p = 0.70; target vessel revascularization: 8.6% vs. 9.4%, p = 0.87). There were no significant interactions between DM status and stent type with respect to the outcomes measured, and the relative efficacy/safety of ZES and PES were similar among insulin- and noninsulin-requiring subgroups.. One-year clinical outcomes were similar among DM patients treated with ZES and PES in the ENDEAVOR IV trial. These findings parallel the overall trial results, which demonstrated similar efficacy and safety of ZES and PES for single de novo coronary lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Hypoglycemic Agents; Insulin; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Prospective Studies; Prosthesis Design; Severity of Illness Index; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome; United States

The RESOLUTE trial examined the safety and efficacy of a next-generation zotarolimus-eluting coronary stent, Resolute (Medtronic CardioVascular Inc., Santa Rosa, California).. Revascularization benefits associated with current drug-eluting stents are often diminished in the presence of complex coronary lesions and in certain patient cohorts. Resolute uses a new proprietary polymer coating that extends the duration of drug delivery to match the longer healing duration often experienced in more complex cases.. The RESOLUTE trial was a prospective, nonrandomized, multicenter study of the Resolute stent in 139 patients with de novo coronary lesions with reference vessel diameters > or =2.5 and < or =3.5 mm and lesion length > or =14 and < or =27 mm. The primary end point was 9-month in-stent late lumen loss by quantitative coronary angiography. Secondary end points included major adverse cardiac events (MACE) at 30 days, 6, 9, and 12 months; acute device, lesion, and procedure success; and 9-month target vessel failure (TVF), target lesion revascularization (TLR), stent thrombosis, neointimal hyperplastic (NIH) volume, and percent NIH volume obstruction.. The 9-month in-stent late lumen loss was 0.22 +/- 0.27 mm. Cumulative MACE were 4.3%, 4.3%, 7.2%, and 8.7% at 30 days, 6, 9, and 12 months, respectively. Acute lesion, procedure, and device success rates were 100.0%, 95.7%, and 99.3%, respectively. At 9 months, TLR was 0.0%, TVF was 6.5%, stent thrombosis was 0.0%, NIH volume was 6.55 +/- 7.83 mm(3), and percent NIH volume obstruction was 3.73 +/- 4.05%.. In this feasibility study, the Resolute stent demonstrated low in-stent late lumen loss, minimal neointimal hyperplastic ingrowth, low TLR, no stent thrombosis, and acceptable TVF and MACE. (The RESOLUTE Clinical Trial; NCT00248079).

Topics: Aged; Angioplasty, Balloon, Coronary; Australia; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Hyperplasia; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; New Zealand; Prospective Studies; Prosthesis Design; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional; United States

Drug-eluting stents (DESs) are increasingly used for treatment of acute ST-segment elevation myocardial infarction (STEMI), but there are few comparisons of outcomes of various types of DES. We compared the efficacy and safety of zotarolimus-eluting stents (ZESs), sirolimus-eluting stents (SESs), and paclitaxel-eluting stents (PESs) in primary intervention for STEMI. This multicenter, prospectively randomized ZEST-AMI trial included 328 patients at 12 medical centers who were randomly assigned to ZES (n = 108), SES (n = 110), or PES (n = 110) deployment. The primary end point was major adverse cardiac events (death, MI, and ischemia-driven target vessel revascularization) at 12 months. Secondary end points included the individual components of the primary end point, late loss, angiographic restenosis, and stent thrombosis. Baseline clinical and angiographic characteristics were well matched. In-segment late loss (0.28 +/- 0.42 vs 0.46 +/- 0.48 vs 0.47 +/- 0.50 mm, respectively, p = 0.029) and restenosis rate (2.7% vs 15.9% vs 12.3%, respectively, p = 0.027) at 8 months were lowest in the SES group compared to the ZES and PES groups. At 12 months, cumulative incidence rates of primary end points in the ZES, SES, and PES groups were 11.3%, 8.2%, and 8.2%, respectively (p = 0.834). There were 2 acute (in the SES group) and 5 subacute (2 in the SES group and 3 in the PES group) stent thromboses. Incidence of death, recurrent MI, or ischemia-driven target vessel revascularization did not differ among the 3 groups. In conclusion, despite the difference in restenosis rate, the efficacy and safety of the 3 different DESs showed similar, acceptable results in the treatment of STEMI.

Topics: Angioplasty, Balloon, Coronary; Aspirin; Cardiovascular Agents; Clopidogrel; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Paclitaxel; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Sirolimus; Ticlopidine

We sought to investigate the long-term efficacy of oral sirolimus therapy and its impact on the incidence of de novo malignancies in the OSIRIS (Oral Sirolimus to Inhibit Recurrent In-Stent Stenosis) trial population.. The OSIRIS trial showed a significant reduction of angiographic restenosis with an oral adjunctive sirolimus treatment for in-stent restenosis. The long-term efficacy of oral sirolimus therapy is unknown.. Three hundred patients with in-stent restenosis were randomly assigned to receive placebo, a cumulative loading dose of 8 mg (usual-dose), or 24 mg (high-dose) of sirolimus over 3 days (2 days before and the day of intervention) followed by maintenance therapy of 2 mg/day for 7 days. The primary outcome of this analysis was the incidence of composite of death, myocardial infarction, and target vessel revascularization at 4-year follow-up. Secondary outcome was the incidence of newly diagnosed malignancies.. No significant differences were observed between placebo, usual-, and high-dose sirolimus treatment groups regarding primary outcome (33.3%, 39.4%, and 31.3%, respectively; p = 0.46), death (5.9%, 9.1%, and 11.1%, respectively; p = 0.41), target vessel revascularization (30.4%, 30.3%, and 22.2%, respectively; p = 0.33), and rate of newly diagnosed malignancies (7.8%, 3.0%, and 11.1%, respectively; p = 0.09).. The benefit in the reduced need for repeat intervention observed at 1 year with high-dose oral sirolimus therapy was attenuated over 4 years. Moreover, this regimen was associated with numerical yet not a significant increase in newly diagnosed malignancies without augmenting the malignancy-induced risk of death. (Oral Sirolimus for In-Stent Restenosis [OSIRUS] trial; NCT00859183).

Topics: Administration, Oral; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Double-Blind Method; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Middle Aged; Myocardial Infarction; Neoplasms; Risk Assessment; Sirolimus; Time Factors

In a number of coronary bifurcation lesions, both the main vessel and the side branch need stent coverage. Using sirolimus eluting stents, we compared 2 dedicated bifurcation stent techniques, the crush and the culotte techniques in a randomized trial with separate clinical and angiographic end-points.. A total of 424 patients with a bifurcation lesion were randomized to crush (n=209) and culotte (n=215) stenting. The primary end point was major adverse cardiac events; cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis after 6 months. At 6 months there were no significant differences in major adverse cardiac event rates between the groups; crush 4.3%, culotte 3.7% (P=0.87). Procedure and fluoroscopy times and contrast volumes were similar in the 2 groups. The rates of procedure-related increase in biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group (P=0.08). A total of 324 patients had a quantitative coronary assessment at the index procedure and after 8 months. The angiographic end-points of in-segment and in-stent restenosis of main vessel and/or side branch after 8 months were found in 12.1% versus 6.6% (P=0.10) and in 10.5% versus 4.5% (P=0.046) in the crush and culotte groups, respectively.. Both the crush and the culotte bifurcation stenting techniques were associated with similar and excellent clinical and angiographic results. Angiographically, there was a trend toward less in-segment restenosis and significantly reduced in-stent restenosis following culotte stenting.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Denmark; Drug-Eluting Stents; Female; Finland; Humans; Kaplan-Meier Estimate; Latvia; Male; Middle Aged; Myocardial Infarction; Norway; Prosthesis Design; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

The newly developed Nobori coronary stent coated with a bioresorbable polymer, polylactic acid, and the antiproliferative agent Biolimus A9 has the potential to reduce restenosis by suppressing neointima formation.. We conducted a randomized (2:1), controlled trial comparing the Biolimus A9-eluting stent Nobori and the paclitaxel-eluting stent Taxus Liberté, in 243 patients (153 Nobori and 90 Taxus) at 29 centers in Europe, Asia, and Australia. Patients with previously untreated lesions in up to 2 native coronary arteries were considered for enrollment. The primary end point was in-stent late loss at 9 months, whereas secondary end points included other quantitative coronary angiography parameters, such as in-segment late loss and the rate of restenosis as well as key intravascular ultrasound parameters. Clinical secondary end points were stent thrombosis and composite of major adverse cardiac events comprising death, myocardial infarction, and target vessel revascularization. At 9 months, the in-stent late loss was significantly lower in the Nobori group compared with the Taxus group (0.11+/-0.30 mm versus 0.32+/-0.50 mm) reaching both the primary hypothesis of noninferiority of Nobori stent versus Taxus Liberté stent (P<0.001) and the secondary hypothesis of superiority (P=0.001). This finding was confirmed by a significant reduction in binary restenosis from 6.2% in Taxus to 0.7% in Nobori (P=0.02) and neointimal volume obstruction, detected by intravascular ultrasound, from 5.5+/-7.2% in Taxus to 1.8+/-5.2% in Nobori (P=0.01). The major adverse cardiac events rate was 4.6% in the Nobori and 5.6% in the Taxus cohort of patients. The stent thrombosis rate was 0% in the Nobori arm and 4.4% in the Taxus arm.. The NOBORI 1 clinical trial confirmed its primary hypothesis--noninferiority of the Nobori Biolimus A9-eluting stent versus the Taxus Liberté stent in reducing neointimal proliferation. Both stents showed a low major adverse cardiac events rate in the studied population.

Topics: Angioplasty, Balloon, Coronary; Asia; Australia; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Europe; Female; Humans; Hyperplasia; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prospective Studies; Risk Assessment; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional

This paper reports the 3-year clinical outcomes of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) compared with the TAXUS (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) in the randomized SPIRIT II (Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions) study.. The Xience V EES is a new-generation drug-eluting stent (DES) that might offer advantages over the first-generation DES in terms of improved clinical outcomes and a better safety profile.. The SPIRIT II trial was a multicenter, prospective, randomized, single-blind, clinical trial, randomizing 300 patients with de novo coronary artery lesions in a ratio of 3:1 to either EES or PES. The primary end point was in-stent late loss at 180 days.. At 3-year clinical follow-up cardiac death was numerically lower with EES than PES (0.5% vs. 4.3%, p = 0.056). The observed rate of myocardial infarction was 3.6% for EES and 7.2% for PES (p = 0.31). The rate of ischemia-driven target lesion revascularization was 4.6% and 10.1% for EES and PES, respectively (p = 0.14). Overall, there was a trend for lower major adverse cardiovascular events in the EES group compared with PES (7.2% vs. 15.9%, p = 0.053). The rate of stent thrombosis was low and comparable in both groups (EES 1.0% vs. PES 2.9%).. The present study reports the favorable 3-year clinical outcomes of the EES, which are consistent with the results from other studies of the EES with shorter follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Single-Blind Method; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; United States

We describe the rationale and design for the 'PercutAneous INTervention with biodegradable-polymer based paclitaxel-eluting or sirolimus-eluting versus bare stents for de novo coronary lesions - PAINT trial'.. To evaluate two novel formulations of paclitaxel-eluting stent and the sirolimus-eluting stent against a stent with the same metallic structure but without polymer coating or drug elution.. The PAINT is a multicenter 3-arm randomized trial, conducted in Brazilian tertiary institutions, which included 275 patients allocated for the InfinniumR paclitaxel-eluting stent, the SupralimusR sirolimus-eluting stent or the Milennium MatrixR bare metal stent in a 2:2:1 ratio. Patients had de novo coronary lesions in native vessels with a diameter between 2.5 and 3.5 mm, amenable for treatment with a single stent of 29 mm or less in length. The primary objective was to compare the in-stent late loss at 9 months of both paclitaxel- and sirolimus-eluting versus the late loss of control bare metal stents. Important secondary objectives included the comparison in outcomes between sirolimus and paclitaxel stents, as well as the analysis of the incidence of major adverse cardiac events.. The PAINT trial had a unique design that allowed for the evaluation of the safety and efficacy profiles of two novel drug-eluting stent formulations, with a biodegradable-polymer carrier and releasing paclitaxel or sirolimus, which were compared against a bare metal stent (primary objective). As the drug-eluting stents differed by the drug, but were identical otherwise, the trial also allowed the comparison of the anti-restenosis effects of sirolimus versus paclitaxel (secondary objective).

Topics: Absorbable Implants; Adolescent; Angioplasty, Balloon, Coronary; Brazil; Cardiovascular Agents; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Epidemiologic Methods; Humans; Paclitaxel; Polymers; Prosthesis Design; Sirolimus; Treatment Outcome; Young Adult

Previous randomised studies have shown a significant reduction in restenosis when oral rapamycin (OR) is administered to patients undergoing bare metal stent (BMS) implantation. How this regimen compares to drug eluting stents (DES) is unknown.. Two-hundred patients with de novo coronary lesions were randomised to treatment with OR plus BMS (100 pts) or with DES (100 pts). OR was given as a bolus of 10 mg per day before PCI followed by daily doses of 3 mg during following 13 days. Primary endpoints were to compare hospital, follow-up and overall cost at one, two, three and five years of follow-up. The secondary endpoints included death, myocardial infarction (MI) and stroke and were analysed as major adverse cardiovascular events (MACCE). Target vessel (TVR) and target lesion revascularisation (TLR) were independently analysed. Costs included procedural resources, hospitalisation, medications, repeat revascularisation procedures and professional fees. Baseline demographic, clinical and angiographic characteristics were similar. At 18.3 +/- 7 months of follow-up, the initial strategy of OR plus BMS resulted in significant cost saving when compared to DES (p=0.0001). TLR rate was 8.2% with DES and 7.0% with OR plus BMS (p=0.84), similarly no differences in TVR rate in both groups was seen (10.6% and 10.5% in OR and DES group respectively, p=0.86). Non-inferiority testing, determined that DES therapy failed to be cost saving compared to OR in all possible cost scenarios.. A strategy of OR plus BMS is cost saving compared to DES in patients undergoing PCI for de novo coronary lesions.

Topics: Administration, Oral; Aged; Angioplasty, Balloon, Coronary; Argentina; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Cost Savings; Drug-Eluting Stents; Female; Health Care Costs; Hospital Mortality; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Metals; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Assessment; Sirolimus; Stents; Stroke; Time Factors; Treatment Outcome

The objective of this study was to assess the non-inferiority, in terms of anti-restenotic efficacy, of both biodegradable-polymer (BP) and polymer-free (PF) stents compared with permanent-polymer rapamycin-eluting (PP; Cypher) stent.. Patients with de novo coronary lesions in native vessels were randomly assigned to receive a BP stent, a PF stent or a PP stent. The primary endpoint was in-stent late lumen loss at follow-up angiogram. A total of 605 patients were enrolled: 202 patients received BP stents, 202 were treated with PP stents, and 201 received PF stents. Repeat angiography was available for 492 patients (81.3%). Mean late lumen loss at 6-8-month angiographic follow-up was 0.17 +/- 0.45 mm in the BP stent group, 0.23 +/- 0.46 mm in the PP cohort, and 0.47 +/- 0.56 mm in the PF stent group. The BP stent met pre-specified criteria for non-inferiority (P < 0.001), whereas the PF stent did not (P = 0.94). There were no differences in safety outcomes.. Both BP and PF stents have a 1-year safety profile similar to that of the PP stent. Whereas the PF stent provided an inferior efficacy, the BP stent is at least as effective as the PP stent in terms of anti-restenotic efficacy.

Topics: Aged; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Polymers; Prospective Studies; Radiography; Sirolimus; Stents; Treatment Outcome; Tubulin Modulators

Patients with diabetes have a higher risk for in-stent restenosis after coronary stent implantation. Drug-eluting stents (DES) are highly effective in reducing in-stent restenosis. Once neointimal hyperplasia is suppressed with DES, the impact of stent underexpansion becomes magnified. The aim of this study was to evaluate DES expansion in patients with diabetes. Ninety-five patients with diabetes were randomized to Cypher Select (n = 48) or Taxus Express-2 (n = 47) stent implantation. Intravascular ultrasound was performed after stent implantation. Stent expansion was defined as the ratio of measured to predicted minimum stent diameter. There was a trend for lower stent expansion in the Cypher Select stent group (0.74 +/- 0.08 vs 0.78 +/- 0.11 in the Taxus Express-2 stent group, p = 0.061). Cypher Select stents achieved a final minimal stent cross-sectional area of 5.5 +/- 1. 8 mm2, compared with 6.4 +/- 1.9 mm2 for Taxus Express-2 stents (p = 0.015). For stents with nominal diameters > or =2.75 mm (Cypher Select n = 40, Taxus Express-2 n = 38), 42.5% of the Cypher Select stents and 10.5% of the Taxus Express-2 stents did not achieve a final minimum stent area of 5 mm2 (p = 0.002). Insulin treatment (relative risk 0.31, 95% confidence interval 0.10 to 0.95, p = 0.041) and stent type (relative risk 0.15, 95% CI 0.04 to 0.53, p = 0.003) were independent predictors of not achieving a minimum stent area >5.0 mm2. In conclusion, an important percentage of DES in patients with diabetes fail to achieve the manufacturers' predicted final minimal stent diameter. Cypher Select stent and insulin treatment were independent predictors of not achieving a minimum stent area >5.0 mm2.

Topics: Aged; Coronary Restenosis; Diabetes Mellitus; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Risk Factors; Sirolimus; Ultrasonography, Interventional

Diabetes has been reported as an independent predictor of restenosis after drug-eluting stent implantation. The purpose of this study was to assess the long-term impact of increased drug dose in sirolimus-eluting stents (SES) on neointimal hyperplasia (NIH) in diabetic patients using volumetric intravascular ultrasound analysis.. The 3D trial is a multicenter, prospective, randomized, feasibility study of double-dose (280 microg/cm2) or conventional single-dose (140 microg/cm2) SES for the treatment of de novo coronary lesions in diabetic patients. To evaluate long-term efficacy, complete serial volumetric analyses (baseline, 6-month and 2-year follow up) were performed in 39 diabetic patients (17 single-dose, 22 double-dose). Each volume was divided by stent length to acquire volume index, expressed as mm3/mm. Percent neointimal volume was calculated as (neointimal volume/stent volume) x 100 at follow up.. Volumetric analysis showed similar results over time between the 2 stent groups (p = NS for all). At 2-year follow up, minimal increases in NIH area and percent NIH were observed in both groups, which translated into a decrease in lumen volume index compared to baseline (p < 0.05 for all). No late-acquired incomplete stent apposition was observed in either group.. The current single dose of sirolimus in SES is effective in inhibiting NIH in diabetic patients up to 2 years. In this patient subset, double-dose SES did not confer additional NIH suppression at 2-year follow up compared to conventional single-dose SES.

Topics: Blood Vessel Prosthesis Implantation; Coronary Restenosis; Diabetic Angiopathies; Dose-Response Relationship, Drug; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Sirolimus; Tunica Intima; Ultrasonography, Interventional

Following stenting for acute myocardial infarction, transcoronary transplantation of granulocyte-colony stimulating factor (G-CSF) mobilized autologous stem cells (ASC) has been shown to result in an increased in-stent restenosis rate of bare metal stents (BMS).. This study sought to compare the extent of neointimal growth in BMS and sirolimus-eluting stents (SES) after primary implantation, and subsequent transcoronary transplantation of G-CSF mobilized stem cells.. Patients with stenting of the left anterior descending coronary artery for acute anterior myocardial infarction were randomly assigned to receive a BMS or SES. Intracoronary stem cell injection was performed after G-CSF application for at least 4 d and cell apheresis. The angiograms obtained after cell transplantation and after 6 mo were analyzed by quantitative coronary angiography.. We performed primary stenting and stem cell transplantion in 16 patients who received a BMS (n = 8) or an SES (n = 8). In 2 patients with a BMS, late stent thrombosis occurred after 58 d and 177 d, respectively. In the remaining patients, control angiography after 6 mo revealed in-stent restenosis of >50% in no patients with SES but in 4 patients with BMS (67%). Late lumen loss and in-stent plaque volume were significantly higher in patients with BMS compared with patients with SES.. Compared with BMS, SES impair in-stent intima hyperplasia after stenting for acute myocardial infarction and transcoronary transplantation of G-CSF mobilized ASC.

Topics: Coronary Restenosis; Drug-Eluting Stents; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Myocardial Infarction; Sirolimus; Stem Cell Transplantation; Stents

Patients with diabetes have increased risk of in-stent restenosis after coronary stent implantation owing to neointimal hyperplasia (NIH). The aim of the study was to evaluate the extent and distribution of NIH with intravascular ultrasound (IVUS) after coronary artery stenting with sirolimus-eluting (Cypher) or paclitaxel-eluting (Taxus) stents in diabetic patients.. One hundred and thirty diabetic patients were randomized to Cypher or Taxus stent implantation. IVUS was performed at 8 month follow-up. NIH volume was significantly reduced in the Cypher group when compared with the Taxus group: median (inter-quartile range) 0.0 (0.0-0.0) vs. 8.0 mm(3) (0.1-33.0), P < 0.001. Per cent NIH volume was also significantly lower in Cypher stents compared with Taxus stents: median (inter-quartile range) 0.0 (0.0-0.0) vs. 7.5% (0.1-27.0), P < 0.001. NIH was covering 5.4% of the stent length in the Cypher stents compared with 46.1% in the Taxus stents (P < 0.001). The incidence of diffuse NIH was significantly higher for Taxus than for Cypher stents (42.9 vs. 3.5%, P < 0.001). Taxus stents had more often NIH at the proximal stent edge compared with Cypher stents (45.1 vs. 7%, P < 0.001) and no Cypher stents had NIH at the distal stent edge compared with 35.5% of the Taxus stents (P < 0.001).. In diabetic patients, the Cypher stent, compared with the Taxus stent, inhibited NIH more effectively and had a more focal NIH pattern including less involvement of the stent edges.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Treatment Outcome; Tunica Intima; Ultrasonography

We investigated whether routine T-stenting reduces restenosis of the side branch as compared with provisional T-stenting in patients with de novo coronary bifurcation lesions.. Our randomized study assigned 101 patients with a coronary bifurcation lesion to routine T-stenting with sirolimus-eluting stents (SES) in both branches and 101 patients to provisional T-stenting with SES placement in the main branch followed by kissing-balloon angioplasty and provisional SES placement in the side branch only for inadequate results. Primary endpoint was per cent diameter stenosis of the side branch at 9 month angiographic follow-up. Angiographic follow-up in 192 (95%) patients revealed a per cent stenosis of the side branch of 23.0 +/- 20.2% after provisional T-stenting (19% with side-branch stent) and of 27.7 +/- 24.8% (P = 0.15) after routine T-stenting (98.2% with side-branch stent). The corresponding binary restenosis rates were 9.4 and 12.5% (P = 0.32), prompting re-intervention in 5.0 and 7.9% (P = 0.39), respectively. In the main branch, binary restenosis rates were 7.3% after provisional and 3.1% after routine T-stenting (P = 0.17). The overall 1 year incidence of target lesion re-intervention was 10.9% after provisional and 8.9% after routine T-stenting (P = 0.64).. Routine T-stenting with SES did not improve the angiographic outcome of percutaneous coronary intervention of coronary bifurcation lesions as compared with stenting of the main branch followed by kissing-balloon angioplasty and provisional side-branch stenting.

Topics: Aged; Angioplasty, Balloon; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Sirolimus; Treatment Outcome

To compare the effects of sirolimus-eluting (SES) versus bare metal stents (BMS) on 6-month in-stent late luminal loss (LLL) and 1-year major adverse cardiac events (MACE) in diabetics undergoing percutaneous coronary interventions.. In studies of unselected patients, coronary restenosis rates have been lower with SES than with BMS. Comparisons of SES versus BMS in diabetics with more than one stenosis or more than one vessel disease are few.. This open-label trial randomly assigned 200 diabetics with de novo coronary artery stenoses to receive up to three SES versus BMS in a 2:1 ratio. The patients underwent repeat coronary angiography at 6 months after the index procedure and were followed-up for 1 year. The primary study endpoint was in-stent LLL at 6 months.. Between August 2002 and May 2004, 83 patients (mean age = 60 years) with 128 lesions (mean = 1.5 per patient) were enrolled at four U.S. and seven Asian medical centers. Enrollment was terminated early by the Safety Monitoring Board because of a statistically significant difference in rates of clinical endpoints. The mean in-stent LLL at 6 months was 0.23 mm in SES versus 1.10 mm in BMS recipients (P < 0.001). At 12 months, 8 patients (15%) assigned to SES had experienced MACE versus 12 patients (41%) assigned to BMS (P = 0.006).. In diabetics, the mean 6-month in-stent LLL was significantly smaller, and 12-month MACE rate significantly lower, after myocardial revascularization with SES than with BMS.

Topics: Aged; Angioplasty, Balloon, Coronary; Asia; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Drug-Eluting Stents; Female; Fibrinolytic Agents; Humans; Male; Metals; Middle Aged; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome; United States

We sought to assess the long-term effectiveness and safety of sirolimus-eluting stents (SES) in patients with in-stent restenosis (ISR).. Treatment of patients with ISR remains a challenge. The long-term outcome of patients with ISR treated with SES remains unknown.. The RIBS-II (Restenosis Intra-stent: Balloon angioplasty vs. elective sirolimus-eluting Stenting) study was a randomized trial conducted in 150 patients with ISR (76 SES, 74 balloon angioplasty [BA]). The long-term (>1 year) clinical outcome and pre-specified subgroup analyses were pre-defined secondary study end points.. At 1 year, the event-free survival (death, myocardial infarction, target vessel revascularization [TVR]) was better in the SES group (88% vs. 69%, p < 0.005). Additional long-term (>3 years) clinical follow-up was obtained in 97% of patients (median 3.3 years). After the first year, 3 patients died (1 SES, 2 BA), 5 suffered myocardial infarction (4 SES, 1 BA), and 7 required TVR (4 SES, 3 BA). At last follow-up, definitive/probable/possible stent thrombosis was similar in both groups (2/2/1 SES vs. 1/0/3 BA, p = NS). At 4 years, the event-free survival was 76% in the SES arm and 65% in the BA arm (p = 0.019). On multivariate analysis, SES implantation was an independent predictor of event-free survival. Subgroup analyses were consistent with the main outcome measure.. In patients with ISR, SES implantation remains effective and safe at very long-term clinical follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Sirolimus; Ticlopidine

Percutaneous treatment of coronary bifurcation disease remains challenging. In patient subsets in which a two-stent strategy is necessary, the culotte technique is a widely used method. We sought to examine the clinical and angiographic outcomes of patients treated in this manner at our institution. As quantitative coronary angiographic analysis using standard measurement programmes is problematic, we used a dedicated bifurcation analysis system.. We prospectively enrolled patients undergoing culotte stenting with drug-eluting stents (Cypher, Endeavor, polymer-free rapamycin-eluting, Taxus) in two German centres. Lesions were classified according to the Medina classification. Angiographic follow-up was scheduled between 6 and 12 months post-index procedure. Clinical follow-up was available up to 12 months. Culotte technique was used in 134 lesions in 132 patients. Of these, 124 (92.5%) represented 'true bifurcation' lesion morphology. Kissing balloon inflation was used in 62% of patients. Procedural angiographic success was achieved in all lesions. Follow-up coronary angiography was performed in 108 (81.8%) patients. Median (IQR) late lumen loss was 0.10 (-0.04-0.38) mm in the proximal main vessel, 0.34 (0.03-0.66) mm in the distal main branch, and 0.30 (-0.01-0.72) mm in the side branch. The incidence of binary angiographic restenosis was 22% for the whole bifurcation lesion, 0% in the proximal main vessel, 9.1% in the distal main branch, and 16% in the side branch. At 12 months, 28 of 132 (21%) patients had undergone target lesion revascularization. The incidence of stent thrombosis (at 1 year) was 1.5%. Predictors of angiographic restenosis were older age, increasing bifurcation angle, more severe distal main branch stenosis, and smaller side branch reference diameter; kissing balloon post-dilatation tended to have a protective effect.. The culotte stenting technique is associated with high procedural success and a relatively low risk of angiographic restenosis. Safety results in our cohort were favourable in terms of a low risk of stent thrombosis.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Sirolimus; Treatment Outcome

The aim of this study was to evaluate long-term outcome of patients treated for in-stent restenosis of bare-metal stents (BMS).. Treatment of restenosis of BMS is characterized by high recurrence rates. Vascular brachytherapy (VBT) improved outcome although late catch-up events were documented. Drug-eluting stents tested against VBT in this setting were found superior for at least the first year; superiority at longer follow-up is uncertain.. We evaluated 3-year outcome of the multicenter SISR (Sirolimus-Eluting Stents Versus Vascular Brachytherapy for In-Stent Restenosis) trial, which randomized patients with restenosis of BMS to either a sirolimus-eluting stents (SES) or VBT.. Target vessel failure (cardiac death, infarction, or target vessel revascularization [TVR]) at 9 months as previously reported was significantly improved with SES. Kaplan-Meier analysis at 3 years documented that survival free from target lesion revascularization (TLR) and TVR continues to be significantly improved with SES: freedom from TLR 81.0% versus 71.6% (log-rank p = 0.018), and TVR 78.2% versus 68.8% (log-rank p = 0.022), SES versus VBT. At 3 years, target vessel failure and major adverse cardiac events (death, infarction, emergency coronary artery bypass grafting, or repeat TLR) remained improved with SES, but did not reach statistical significance. There was no statistically significant difference in definite or probable stent thrombosis (3.5% for SES, 2.4% for VBT; p = 0.758).. At 3 years of follow-up, after treatment of in-stent restenosis of BMS, patients treated with SES have improved survival free of TLR and TVR compared with patients treated with VBT. Stent thrombosis rates are not different between the 2 groups but are higher than reported in trials of treatment of de novo lesions.

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Cardiovascular Agents; Coronary Artery Bypass; Coronary Restenosis; Drug-Eluting Stents; Humans; Kaplan-Meier Estimate; Metals; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Design; Recurrence; Risk Assessment; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome; United States

A novel zotarolimus-eluting coronary stent system (ZoMaxx, Abbott Laboratories, Abbott Park, Illinois) was compared with a paclitaxel-eluting coronary stent (Taxus Express2) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. The primary end point was defined as noninferiority of in-segment late lumen loss after 9 months.. The ZoMaxx stent system elutes 10 microg/mm zotarolimus using a phosphorylcholine polymer loaded onto a novel stainless steel stent platform containing a 0.0007-inch inner layer of tantalum.. Twenty-nine investigative sites in Europe, Australia, and New Zealand enrolled 401 patients, 396 of whom received a study stent.. After 9 months, late lumen loss was significantly greater in the ZoMaxx group (in-stent 0.67 +/- 0.57 mm vs. 0.45 +/- 0.48 mm; p < 0.001; in-segment 0.43 +/- 0.60 mm vs. 0.25 +/- 0. 45 mm; p = 0.003), resulting in significantly higher rates of >50% angiographic restenosis (in-stent 12.9% vs. 5.7%; p = 0.03; in-segment 16.5% vs. 6.9%; p = 0.007). The upper bound of the 95% confidence interval on the difference in in-segment late lumen loss between the 2 treatment groups (0.27 mm) exceeded the 0.25 mm value pre-specified for noninferiority. There were no significant differences between ZoMaxx and Taxus-treated groups with respect to target lesion revascularization (8.0% vs. 4.1%; p = 0.14), major adverse cardiac events (12.6% vs. 9.6%; p = 0.43), or stent thrombosis (0.5% in both groups).. After 9 months, the ZoMaxx stent showed less neointimal inhibition than the Taxus stent, as shown by higher in-stent late loss and restenosis by qualitative coronary angiography.

Topics: Aged; Angioplasty, Balloon, Coronary; Australia; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Europe; Female; Humans; Logistic Models; Male; Middle Aged; New Zealand; Paclitaxel; Prospective Studies; Prosthesis Design; Risk Assessment; Severity of Illness Index; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional

It is still controversial whether sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) are equally effective in patients with diabetes. In these patients, multiple individual variables may be responsible for neointimal hyperplasia, thus making difficult the comparison of the two drug-eluting stents (DES).. We designed a prospective, randomized study to compare the efficacy in prevention of restenosis of SES and PES, both implanted in the same diabetic patient with multiple de novo coronary artery lesions undergoing elective percutaneous coronary intervention. We enrolled 60 patients with diabetes with at least two significant de novo angiographic stenoses in different coronary segments. The primary end point was in-stent late luminal loss (LLL) at 8-month angiographic follow-up.. A total of 120 lesions were successfully treated with the randomly assigned DES (SES, n = 60; PES, n = 60). In-stent LLL was lower in the SES than in the PES group (0.26 +/- 0.4 vs. 0.50 +/- 0.6 mm; P = 0.01). Coronary lesions treated with SES presented a reduced in-stent LLL in 40 (68%) patients, while PES resulted in a lower in-stent LLL in 19 (32%) patients (P = 0.0002). At multivariable analysis, the type of DES implanted was the only independent predictor of in-stent LLL (odds ratio 2.3 [95% CI 1.1-5.0]; P = 0.03).. SES directly compared with PES in the same diabetic patient is associated with a decrease in the extent of in-stent LLL at 8 months, suggesting a reduced risk of restenosis.

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Agents; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Prospective Studies; Sirolimus

Wall shear stress (WSS) has been associated with neointimal hyperplasia (NIH) following bare metal stent (BMS) implantation. Drug-eluting stents (DES) almost abolish NIH. Conversely, diabetes mellitus amplifies NIH response. The association between WSS and arterial wall response following DES and BMS implantation in diabetic patients remains to be evaluated.. The study involved 20 diabetic patients randomized to BMS (n = 9) or sirolimus-eluting stent (SES; n = 11) implantation in native coronary arteries. A computational fluid dynamic model applied 3D intravascular ultrasound (IVUS) and two-plane angiographic to measure WSS (Pa). IVUS assessments were performed post-procedure and at 9-months follow-up. The target segment encompassed the stent plus 5 mm distal and proximal edges. A total of 93 subsegments were evaluated: in-stent segments divided in three subsegments (proximal, mid and distal; n = 60) and proximal and distal edges (n = 33).. Stent length was similar between BMS (17.4 +/- 7.3 mm) and SES (19.8 +/- 6.8 mm) groups. NIH was observed in all BMS subsegments (n = 27) versus one subsegment in the SES group (n = 33). WSS ranged from 0.52 to 4.20 Pa in the BMS and from 0.42 to 3.06 Pa in the SES group. There was no correlation between WSS and NIH in either stent group. In addition, there were no correlation between the change of external elastic membrane (EEM) or plaque growth at the edges and WSS.. WSS was not associated with NIH after implantation of SES or BMS in diabetic patients. Plaque growth or the change of EEM at the edges were not associated with WSS either.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Computer Simulation; Coronary Angiography; Coronary Circulation; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Female; Hemorheology; Humans; Hyperplasia; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Metals; Middle Aged; Models, Cardiovascular; Pulsatile Flow; Sirolimus; Stents; Stress, Mechanical; Time Factors; Treatment Outcome; Ultrasonography, Interventional

We assessed the effectiveness and safety of the sirolimus-eluting stent (SES) in the treatment of chronic total coronary occlusions.. Chronic total occlusions (CTO) of coronary vessels have an unacceptable high restenosis rate of approximately 50% after stenting. Few data exist about the performance of drug eluting stents (DES) in the treatment of CTO.. All coronary interventions using the Cypher stent performed at 122 centers engaged in the German Cypher registry between April 2002 and December 2004 were analyzed; a total of 5,344 patients; 374 with and 4,970 without CTO were compared.. There was no significant difference between both groups regarding demographics, coronary status and left ventricular function. Patients in the CTO group had a higher level of angina symptoms, the coronary lesions were more complex and the stents used were smaller and longer than in the No-CTO group. The In-hospital outcome was similar in both groups, with importantly no difference regarding mortality and complications. Stenting was as successful in the CTO as in the No-CTO group; during a follow-up of 6.6 months we found no significant difference regarding the rate of mortality, complications, and revascularization between both groups.. Implantation of the Cypher stent reduces the restenosis rate and seems to be a safe and effective tool for the treatment of chronic total coronary occlusions.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis; Chronic Disease; Coronary Occlusion; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Female; Germany; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Prospective Studies; Registries; Sirolimus; Treatment Outcome

The purpose of this study was to investigate the vascular response of zotarolimus-eluting stent (ZES) and sirolimus-eluting stent (SES) using serial intravascular ultrasound (IVUS).. Data were obtained from the Endeavor Drug-Eluting Coronary Stent System Versus the Center Siromlimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR) III trial, a randomized study comparing ZES and SES for the treatment of de novo native coronary artery lesions. Serial (baseline and 8-month follow-up) IVUS was available in 258 patients (190 ZES, 68 SES).. At 8 months, ZES had greater percentage of neointimal volume index (ZES 1.1 +/- 0.8 mm3/mm vs SES 0.2 +/- 0.1 mm3/mm, P < .01), resulting in smaller lumen volume index (6.0 +/- 2.0 mm3/mm vs 7.0 +/- 2.1 mm3/mm, P < .05). Zotarolimus-eluting stents showed larger IVUS-detectable neointimal coverage over stent surface (50.2% vs 10.5%, P < .01) and greater mean neointimal thickness (0.19 +/- 0.07 mm vs 0.10 +/- 0.06 mm, P < .01). Zotarolimus-eluting stents had a significantly lower incidence of late-acquired incomplete stent apposition.. Zotarolimus-eluting stent is associated with a significantly greater amount of neointimal hyperplasia compared with SES. This amount of hyperplasia in ZES is distributed throughout the stent at 8-month follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Probability; Reference Values; Risk Assessment; Sensitivity and Specificity; Single-Blind Method; Sirolimus; Survival Rate; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional; Vascular Patency

Although restenosis after successful coronary stenting is associated with changes in adhesion molecules and chemokines, it is unclear whether the differential effects of these molecules between a bare metal stent (BMS) and sirolimus-eluting stent (SES) may help to prevent coronary restenosis. The aim of this clinical study was to compare the expression levels of those molecules after elective placement of either a BMS or SES.. The subjects included 32 consecutive patients with stable angina who had undergone successful coronary stenting and who randomly received either a BMS (n=16) or SES (n=16). Quantitative angiographic analysis 6 months after stenting showed that the minimal lumen diameter was significantly greater in the SES as compared to the BMS group, while the percent diameter stenosis and in-stent lumen loss were significantly lower. Plasma monocyte chemotactic protein-1 (MCP-1) increased significantly after 14 days and 6 months and monocyte CCR2 expression increased 24 hr and 48 hr after stenting in the BMS but not the SES group. Changes in plasma MCP-1 (DeltaMCP-1) within 6 months after stenting correlated significantly with in-stent lumen loss. The DeltaMCP-1 (between 6 months and baseline) was significantly related only to the lumen loss (r=0.443, p=0.023), which suggests that the reduction of MCP-1 is the best contributor to decreased lumen loss.. These data suggest that reduction in MCP-1 production by SES may be one mechanism to prevent restenosis after coronary stenting.

Topics: Aged; Angina Pectoris; Autoantigens; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Gene Expression; Humans; Immunosuppressive Agents; Male; Middle Aged; Receptors, CCR2; Sirolimus; Stents

We compared sirolimus-eluting stent (SES) implantation and intracoronary brachytherapy (ICBT) for diffuse bare metal in-stent restenosis (ISR) to identify more effective treatment modality.. Patients (n=129) with diffuse ISR (lesion length > or = 10 mm) were randomly assigned to either SES implantation (n=65, group I) or beta-radiation with 188Re-MAG(3)-filled balloon (n=64, group II). The radiation dose was 20 Gy at a depth of 1.0 mm into the vessel wall. The primary end point was late loss in analysis segment at 6 months. The secondary end points were 6-month angiographic restenosis and 1-year major adverse cardiac events (MACE) including myocardial infarction (MI), cardiac death, and target lesion revascularization (TLR).. Baseline characteristics were similar between two groups. The lesion length was 27.52+/-13.98 mm in group I and 27.75+/-14.25 mm in group II (p=0.927). Late loss in analysis segment at 6 months was smaller in group I than in group II (0.15+/-0.62 vs. 0.55+/-0.69 mm, p=0.003). Angiographic restenosis for analysis segment at 6 months was 8.0% (4/50) in group I and 30.2% (16/53) in group II (p=0.006). One MI and two deaths (all from group I) occurred during follow-up. TLR (4.6% vs. 18.8%, p=0.014) and MACEs (7.7% vs. 18.8%, p=0.073) were lower in group I than group II at 1 year.. Compared to ICBT, SES implantation for diffuse bare metal ISR showed less late loss, lower restenosis, and a trend toward lower 1-year MACEs. SES implantation appears to be superior to ICBT for treating diffuse ISR.

Topics: Aged; Brachytherapy; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Sirolimus

The aim was to compare 2-year outcomes with the routine use of drug-eluting stents (DES) (>75% "off-label") with a comparable group treated with bare-metal stents (BMS).. Safety concerns >1 year from implantation have been raised about DES used "off-label." There are limited data comparing DES and BMS in "off-label" patients.. Clinical outcomes (nonfatal myocardial infarction [MI], all-cause mortality) were assessed in 1,164 consecutive patients who received BMS in the year before introduction of DES at Wake Forest University Baptist Medical Center and 1,285 consecutive patients who received DES after it became our routine choice. "On-label" stent use was defined as treatment for a single de novo lesion <30 mm, without recent MI or other major illnesses.. At 2 years, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.77 (95% confidence interval [CI] 0.62 to 0.95), for all-cause mortality 0.71 (0.54 to 0.92), and stent thrombosis (ST) 0.97 (0.49 to 1.91). "On-label" stent procedures were associated with lower risk of MI, death, and ST than "off-label" stent procedures. For "off-label" stent procedures, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.78 (95% CI 0.62 to 0.98), all-cause mortality 0.72 (0.54 to 0.94), and ST 0.91 (0.46 to 1.80). The hazard of nonfatal MI or death was similar or lower for DES than BMS in high-risk subgroups, including renal failure and recent MI.. The routine clinical use of drug-eluting stents for "off-label" indications was associated with lower nonfatal MI and death at 2 years than in a comparable group of patients treated with BMS.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Blood Vessel Prosthesis Implantation; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Heparin; Hirudins; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Proportional Hazards Models; Recombinant Proteins; Risk Factors; Secondary Prevention; Sirolimus; Treatment Outcome

Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents.. In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE (defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% (14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% (7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years.. Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patients.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Male; Myocardial Revascularization; Paclitaxel; Sirolimus; Treatment Outcome; Tubulin Modulators

Although previous studies have indicated that vascular endothelial growth factor (VEGF) plays an important role in the vascular-healing process after stent implantation, its effect on in-stent restenosis is unclear. We assessed VEGF serum protein levels and gene expression in peripheral monocytes in relation to in-stent restenosis after implantation of sirolimus-eluting (SES) and bare metal stents (BMS) in a non-blinded, randomized study.. Forty-two patients (28 men, age 62 +/- 11 years) with stable angina, who underwent elective single-vessel percutaneous coronary intervention, were randomized to SES (n = 21) or BMS (n = 21) implantation. VEGF protein levels in the BMS group showed an increasing trend (P = 0.083), whereas in the SES group they decreased significantly (P = 0.002). BMS induced up-regulation of VEGF mRNA levels, whereas for SES down-regulation was observed. There was no correlation between serum levels and late luminal loss. A significant correlation was found between VEGF gene expression and late luminal loss in both groups (BMS: r = 0.98, P < 0.001; SES: r = 0.65, P = 0.002).. SES, in comparison with BMS, results in lower VEGF protein levels and gene expression in peripheral monocytes. The latter shows a positive relationship with in-stent late-luminal loss, suggesting an essential role in the reduced in-stent restenosis seen in SES.

Topics: Coronary Restenosis; Dose-Response Relationship, Drug; Down-Regulation; Female; Gene Expression; Humans; Immunosuppressive Agents; Male; Middle Aged; Monocytes; Sirolimus; Stents; Tubulin Modulators; Vascular Endothelial Growth Factor A

A fully bioabsorbable drug-eluting coronary stent that scaffolds the vessel wall when needed and then disappears once the acute recoil and constrictive remodelling processes have subsided has theoretical advantages. The bioasorbable everolimus-eluting stent (BVS) has a backbone of poly-L-lactic acid that provides the support and a coating of poly-D,L-lactic acid that contains and controls the release of the antiproliferative agent everolimus. We assessed the feasibility and safety of this BVS stent.. In this prospective, open-label study we enrolled 30 patients who had either stable, unstable, or silent ischaemia and a single de-novo lesion that was suitable for treatment with a single 3.0 x 12 mm or 3.0 x 18 mm stent. Patients were enrolled from four academic hospitals in Auckland, Rotterdam, Krakow, and Skejby. The composite endpoint was cardiac death, myocardial infarction, and ischaemia-driven target lesion revascularisation. Angiographic endpoints were available for 26 patients and intravascular-ultrasound endpoints for 24 patients. Clinical endpoints were assessed in all 30 patients at 6 and 12 months. In a subset of 13 patients, optical coherence tomography was undertaken at baseline and follow-up. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00300131.. Procedural success was 100% (30/30 patients), and device success 94% (29/31 attempts at implantation of the stent). At 1 year, the rate of major adverse cardiac events was 3.3%, with only one patient having a non-Q wave myocardial infarction and no target lesion revascularisations. No late stent thromboses were recorded. At 6-month follow-up, the angiographic in-stent late loss was 0.44 (0.35) mm and was mainly due to a mild reduction of the stent area (-11.8%) as measured by intravascular ultrasound. The neointimal area was small (0.30 [SD 0.44] mm2), with a minimal area obstruction of 5.5%.. This study shows the feasibility of implantation of the bioabsorbable everolimus-eluting stent, with an acceptable in-stent late loss, minimal intrastent neointimal hyperplasia, and a low stent area obstruction.. Abbott Vascular.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Safety; Sirolimus; Ultrasonography

A thin, cobalt-chromium stent eluting the antiproliferative agent everolimus from a nonadhesive, durable fluoropolymer has shown promise in preliminary studies in improving clinical and angiographic outcomes in patients with coronary artery disease.. To evaluate the safety and efficacy of an everolimus-eluting stent compared with a widely used paclitaxel-eluting stent.. The SPIRIT III trial, a prospective, randomized, single-blind, controlled trial enrolling patients at 65 academic and community-based US institutions between June 22, 2005, and March 15, 2006. Patients were 1002 men and women undergoing percutaneous coronary intervention in lesions 28 mm or less in length and with reference vessel diameter between 2.5 and 3.75 mm. Angiographic follow-up was prespecified at 8 months in 564 patients and completed in 436 patients. Clinical follow-up was performed at 1, 6, 9, and 12 months.. Patients were randomized 2:1 to receive the everolimus-eluting stent (n = 669) or the paclitaxel-eluting stent (n = 333).. The primary end point was noninferiority or superiority of angiographic in-segment late loss. The major secondary end point was noninferiority assessment of target vessel failure events (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months. An additional secondary end point was evaluation of major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization) at 9 and 12 months.. Angiographic in-segment late loss was significantly less in the everolimus-eluting stent group compared with the paclitaxel group (mean, 0.14 [SD, 0.41] mm vs 0.28 [SD, 0.48] mm; difference, -0.14 [95% CI, -0.23 to -0.05]; P < or = .004). The everolimus stent was noninferior to the paclitaxel stent for target vessel failure at 9 months (7.2% vs 9.0%, respectively; difference, -1.9% [95% CI, -5.6% to 1.8%]; relative risk, 0.79 [95% CI, 0.51 to 1.23]; P < .001). The everolimus stent compared with the paclitaxel stent resulted in significant reductions in composite major adverse cardiac events both at 9 months (4.6% vs 8.1%; relative risk, 0.56 [95% CI, 0.34 to 0.94]; P = .03) and at 1 year (6.0% vs 10.3%; relative risk, 0.58 [95% CI, 0.37 to 0.90]; P = .02), due to fewer myocardial infarctions and target lesion revascularization procedures.. In this large-scale, prospective randomized trial, an everolimus-eluting stent compared with a paclitaxel-eluting stent resulted in reduced angiographic late loss, noninferior rates of target vessel failure, and fewer major adverse cardiac events during 1 year of follow-up.. clinicaltrials.gov Identifier: NCT00180479.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Logistic Models; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prospective Studies; Single-Blind Method; Sirolimus; Ultrasonography, Interventional

Drug eluting stents (DES) have been shown to reduce restenosis compared with bare metal stents in bifurcated lesions. The aim of this study was to evaluate the long-term clinical outcomes of patients with bifurcated lesions treated by 3 different DES.. Consecutive patients with symptomatic coronary artery disease on one bifurcated lesion with SB>2.25 mm (on visual estimation) undergoing at the Department of Cardiology of the Catholic University of Rome, Italy were screened. Patients treated with Sirolimus-eluting stent (Cypher Select; SES Group), Tacrolimus-eluting stent (Taxus-Libertè; TA Group) and Zotarolimus-eluting stent (Endeavor Driver; ZOT Group) were enrolled in the study. Clinical and angiographic characteristics of all patients were prospectively recorded. Major adverse clinical events (MACE), including death, acute myocardial infarction (MI) or target lesion revascularization (TVR) by either percutaneous coronary intervention (PCI) or coronary surgery were recorded during the follow-up. Incidence of definite or probable stent thrombosis was calculated according to the ARC criteria.. Two hundred and forty-one consecutive patients were enrolled (89 Group CY, 98 Group TA and 54 Group EN). Length of follow-up was 235+/-60 days. Baseline clinical and angiographic characteristic were similar across the groups. The adopted technique for stent implantation was provisional stenting (73.4%), T-stenting technique (7%), crush (7%) and V-stenting (2.6%). The rate of patients finally treated with two stents was similar among groups. The cumulative rate of MACE (9% SES, 12% TA, 11% ZOT: P=0.7) and of TVR (2% SES, 9% TA, 7% ZOT) was similar among groups. No definite stent thrombosis was observed during follow-up, while 1 probable stent thrombosis was observed in TA group.. The clinical outcome of bifurcated lesions using DES and mainly a technique of single stent implantation is good. In the present observational study, clinical adverse events did not differ in patients with bifurcated lesions treated by Cypher, Taxus or Endeavor stent implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Risk Factors; Rome; Sirolimus; Tacrolimus; Treatment Outcome

Our purpose was to evaluate the long-term use of sirolimus-eluting stents (SES) and bare-metal stents (BMS) in patients with complex coronary artery lesions.. Although the use of SES has proved to be effective in patients with simple coronary artery lesions, there are limited data of the long-term outcome of patients with complex coronary artery lesions.. We randomly assigned 322 patients with total coronary occlusions or lesions located in bifurcations, ostial, or angulated segments of the coronary arteries to have SES or BMS implanted.. At 3 years, major adverse cardiac events had occurred in 20 patients (12%) in the SES group and in 59 patients (38%) in the BMS group (p < 0.001). Four versus 2 patients suffered a cardiac death (p = NS), and 5 versus 1 died of a noncardiac disease (p = NS) in the SES versus the BMS group. Six patients in the SES group versus 15 patients in the BMS group suffered a myocardial infarction (p < 0.05) during the 3-year observation period, and target lesion revascularization was performed in 8 patients (4.9%) versus 53 patients (33.8%), respectively (p < 0.001); of these, 4 in the SES versus 7 in the BMS group were performed between 1 and 3 years after the index treatment (p = NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (p = NS); very late stent thrombosis was observed in 4 versus 1 patient.. A continued benefit was observed up to 3 years after implantation of SES in patients with complex coronary artery lesions. The rate of late adverse events was similar in the 2 groups, and stent thromboses occurred rarely after 1 year. (Sirolimus Eluting Stents in Complex Coronary Lesions [SCANDSTENT]; NCT00151658)

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Sirolimus; Stents; Treatment Outcome

Metallic allergy is associated with restenosis following bare metal stent implantation, but the impact of metallic allergy on the outcome after implantation of drug-eluting stents (DES) has not been investigated.. The present study group consisted of 88 consecutive patients (109 lesions) who underwent percutaneous coronary intervention with sirolimus-eluting stents (SES). Follow-up angiography was obtained at 8 months in all patients. At that time, the patients underwent epicutaneous patch tests for nickel, chromate, molybdenum, manganese, and titanium, which were evaluated after 48 h of contact. The patch test was positive in 14 patients (16%) (5 for manganese, 3 for nickel, 1 for chromate, 1 for Nickel and manganese, and 4 for manganese and chromate). The binary restenosis rate in the patients with a positive patch test was similar to those with negative patch test (6.3% vs 6.5%, p=0.98). Serial quantitative coronary angiography analyses identified no significant differences in late lumen loss of in-stent segments between patients with positive patch test and those with negative patch test (0.19+/-0.49 mm vs 0.12+/-0.48 mm, p=0.55).. SES prevent restenosis irrespective of metallic allergy. The classic relationship between metallic allergy and in-stent restenosis, seen with bare metal stents, does not appear to arise with DES, possibly because of the immunosuppressive effect of sirolimus.

Topics: Aged; Angioplasty, Balloon, Coronary; Chromates; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hypersensitivity; Immunosuppressive Agents; Male; Manganese; Metals; Middle Aged; Molybdenum; Nickel; Patch Tests; Sirolimus; Titanium; Treatment Outcome; Tunica Intima

Drug-eluting stents have been shown to reduce restenosis in many types of lesions. The purpose of this article is to assess the efficacy of sirolimus- and paclitaxel-eluting stents in patients with bifurcation lesions.. Between June 2003 and October 2004, 205 patients were enrolled in a prospective randomized trial; 103 patients were assigned to sirolimus stents and 102 patients to paclitaxel stents. All patients were treated by provisional T-stenting.. There were no differences between groups in terms of age, risk factors, clinical condition, location of the bifurcation lesion, or other technical factors. Angiographic data and immediate results were also similar in both groups. Three patients developed inhospital non-Q-wave acute myocardial infarction (2 from the sirolimus group and 1 from the paclitaxel group). Follow-up angiography was obtained in 109 patients (53%). In the sirolimus group, 5 patients developed restenosis (9%): 1 at the main vessel, 2 at the side branch, and 2 in both branches. In contrast, 16 patients from the paclitaxel group had restenosis (29%): 6 at the main vessel, 5 at the side branch, and 5 in both branches. Target lesion revascularization at 24 +/- 5 months post stenting occurred in 4 patients from the sirolimus group (4%) and in 13 from the paclitaxel group (13%) (P < .05). Late loss at the main vessel in the sirolimus group patients was 0.31 +/- 0.59 versus 0.60 +/- 0.77 mm in patients from the paclitaxel group (P < .05).. Patients with bifurcation lesions treated by sirolimus showed significantly lower rates of late loss, restenosis and target lesion revascularization than patients treated with paclitaxel-eluting stents.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Creatine Kinase; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Prospective Studies; Sirolimus; Stents; Troponin I; Ultrasonography, Interventional

Late loss (LL) has been a fundamental angiographic end-point in drug-eluting stents (DES) clinical trials. However, calculation of LL may be affected by a mismatch between post-procedure (PO) and follow-up (FU) sites of the minimal lumen diameter (MLD). Our aims were to investigate the incidence and methodological implications of the relocation of MLD after bare metal (BMS), sirolimus-eluting (SES), and paclitaxel-eluting (PES) stent implantation. Data from DIABETES I and II trials, which involved diabetic patients treated with BMS, SES, and PES, were analyzed. Angiographic data with matched projections between PO and 9-month angiographic FU were included. In-stent, in-lesion, and in-segment analyses included conventional and customized sub-segmental (5-mm/subsegment) methodology. MLD relocation was considered when the sites of MLD shifted a distance >> the intrinsic variability of the method. Conventional LL, site matched LL, maximal LL (MaxLL), and average LL (AvgLL) were calculated. Relationships between various LL and 1-year target lesion revascularization (TLR) were investigated. Post MLD was located distally, outside the stent, in > or =65% of the analyses. At FU, MLD relocation occurred in 70.5% (BMS), 40% (SES), and 35% (PES). MLD shifted > or =11 mm on average, mainly towards the stented segment. MLD relocation still occurred in 42.8% (BMS), 33.7% (SES), and 36.4% (PES), when analysis was restricted to in-stent segment. Among LL measurements, MaxLL showed the best association with TLR rates. Relocation of the MLD is a frequent phenomenon after both BMS and DES, and should be taken into account when calculating LL. Comprehensive LL analyses, including MaxLL and AvgLL, provides a better appraisal of the biological and clinical effectiveness of DES.

Topics: Aged; Analysis of Variance; Coronary Angiography; Coronary Restenosis; Diabetes Complications; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Paclitaxel; Prospective Studies; ROC Curve; Sirolimus; Stents; Treatment Outcome

The use of the Endeavor stent might reduce restenosis and stent thrombosis at 9 months.. Patients (n =1,197) treated for single coronary artery stenosis were enrolled in a prospective, randomized, double-blind study and randomly assigned to receive the Endeavor zotarolimus-eluting phosphorylcholine polymer-coated stent (n= 598) or the same bare metal stent but without the drug or the polymer coating (n=599).. The 2 groups were well matched in baseline characteristics. Diabetes was present in 20.1% of patients; the mean reference vessel diameter was 2.75 mm; and the mean lesion length was 14.2 mm. The primary end point of target vessel failure at 9 months was reduced from 15.1% with the bare metal stent to 7.9% with the Endeavor (P=0.0001), and the rate of major adverse cardiac events was reduced from 14.4% with the bare metal stent to 7.3% with the Endeavor (P=0.0001). Target lesion revascularization was 4.6% with Endeavor compared with 11.8% with the bare metal stent (P=0.0001). The rate of stent thrombosis was 0.5% with the Endeavor, which was not significantly different from 1.2% with the bare metal stent. In 531 patients submitted to angiographic follow-up, late loss was reduced from 1.03+/-0.58 to 0.61+/-0.46 (P<0.001) in stent and from 0.72+/-0.61 to 0.36+/-0.46 (P<0.001) in segment. The rate of in-segment restenosis was reduced from 35% to 13.2% with Endeavor (P<0.0001). There was no excessive edge stenosis, aneurysm formation, or late acquired malposition by intravascular ultrasound imaging. Differences in clinical outcome were maintained at 12 and 24 months (P<0.0001).. Compared with bare metal stents, the Endeavor stent is safe and reduces the rates of clinical and angiographic restenosis at 9, 12, and 24 months.

Topics: Aged; Australia; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Double-Blind Method; Drug Delivery Systems; Equipment Design; Europe; Female; Humans; Israel; Male; Middle Aged; New Zealand; Pacific Islands; Phosphorylcholine; Prospective Studies; Sirolimus; Stents; Treatment Outcome

To see whether use of a sirolimus-eluting stent (SES) is superior to a third-generation thin-strut, cobalt-chromium stent (CCS) in terms of in-segment late loss at 9 months in patients with symptomatic coronary artery disease.. Stent-strut thickness has been shown to be strictly related with risk of in-stent restenosis, but available demonstrations of the angiographic efficacy of SES have been based on comparisons with thick-strut bare metal control stents.. The primary outcome measure of this single-center, single-blind randomized comparative trial was 9-month in-segment late loss. Eligibility criteria were symptomatic coronary artery disease and target vessel diameter appropriate for implantation a 3-mm stent. Based on a power calculation, 104 patients were randomly assigned to receive a SES (Cypher) or a CCS (Vision).. In-segment late loss was significantly lower in the SES group (0.18 +/- 0.40 mm vs 0.58 +/- 0.51 mm, P < 0.001). Regarding subsidiary outcome measures, in-segment restenosis (at 9 months) was recorded in 10% (5/50) patients treated with SES and 23% (11/48) receiving CCS (P = 0.14). No clinical difference between the two groups was apparent at 12 months. Freedom from target vessel failure at 12 months was 72% for SES patients and 68% for CCS patients (P = 0.65).. In patients with de-novo coronary lesions at medium risk of restenosis the anti-proliferative effect of SES is greater than that of a thin-strut CCS. Nevertheless, the angiographic results of the CCS were rather good. It remains to be seen whether the angiographic superiority of SES can translate into clinical superiority.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prosthesis Design; Research Design; Risk Factors; Single-Blind Method; Sirolimus; Stents; Time Factors; Treatment Outcome

The drug-eluting stent (DES) has been proven its efficacy in randomized trials. But the difference of efficacy between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in unselected patients is in controversy. Therefore, we investigated the clinical and angiographic outcomes of these two types of the DES.. All consecutive patients treated with DES from March 2003 to March 2004 at two centers were analyzed.. We analyzed 440 patients with 519 lesions who were treated with the two types of DES (SES 353 lesions/296 patients, PES 166 lesions/144 patients). PES group had more acute myocardial infarction (AMI) patients. Angiographically, the number of stents per lesion, maximal deployment pressure, stent diameter and the percent residual stenosis after procedure were different between the two groups. Angiographic follow-up was available in 103 patients (71.5%) in the PES group and 208 patients (70.3%) in the SES group. PES showed the higher binary restenosis rate (PES 17.9%, SES 4.5%, p<0.0001) and the larger late loss (PES 0.60x0.83 mm vs. SES 0.16x0.40 mm, p<0.001) than SES. PES was the predictor of binary restenosis at six months (OR 4.67, CI 2.20-9.91). At one year follow-up, PES also had more cardiac events (composites of death of all cause, MI, and target lesion revascularization) than SES (PES 13.9% vs. SES 6.1%, p<0.001). PES was a significant predictor of cardiac events at one year (OR 2.47, CI 1.23-4.95).. SES showed better clinical and angiographic outcomes compared to PES in a daily routine practice of coronary intervention in Koreans.

Topics: Anti-Bacterial Agents; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Korea; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Sirolimus-eluting stents (SESs) recently proved to be superior to bare metal stents (BMSs) in decreasing the need for repeat revascularization in patients with ST-segment elevation myocardial infarction (STEMI) at 1 year. Whether this also holds for paclitaxel-eluting stents (PESs) is currently unclear and the long-term relatively efficacy of the 2 drug-eluting stents is currently unknown. We investigated the 3-year efficacy of SESs and PESs versus BMSs in patients with STEMI. Primary angioplasty was performed in a consecutive group of 505 patients (BMSs in 183, SESs in 186, PESs in 136). At 3 years, the cumulative mortality rate was comparable in the 3 groups: 13.3% in the BMS group, 11.5% in the SES group, and 12.4% in the PES group (nonsignificant for all). The rate of target vessel revascularization (TVR) was 12.0% in the BMS group compared with 8.0% and 7.7% in the SES and PES groups, respectively (p = 0.12 for BMS vs SES, 0.30 for BMS vs PES, 0.62 for SES vs PES). The cumulative incidence of death, MI, or TVR was 25.5% in the BMS group compared with 17.9% and 20.6% in the SES and PES groups, respectively (p = 0.06 for BMS vs SES, 0.32 for BMS vs PES, 0.45 for SES vs PES). Angiographic stent thrombosis occurred in 2.4% of all patients (BMS 1.6%, SES 2.7%, PES 2.9%). In conclusion, in this relatively small consecutive patient cohort, the use of SESs and PESs was no longer associated with significantly lower rates of TVR and major adverse cardiace events in patients with STEMI after 3 years of follow-up. A high frequency of stent thrombosis was observed in the 2 drug-eluting stent groups.

Topics: Angioplasty, Balloon, Coronary; Cause of Death; Clopidogrel; Cohort Studies; Coronary Restenosis; Electrocardiography; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Registries; Retrospective Studies; Sirolimus; Stents; Survival Rate; Ticlopidine; Treatment Outcome

The SIRIUS study was a double-blinded, randomized trial of the sirolimus-eluting stent (SES) to evaluate its effect on the rate of restenosis. The present report is a retrospective analysis of short- and long-term outcomes of SESs compared with bare metal stents (BMSs) in a subgroup of patients with unstable angina enrolled in the trial. Of 1,058 patients randomized in SIRIUS, 533 (50.4%) had unstable angina pectoris and 490 had stable angina. In the unstable angina group, patients treated with SESs and BMSs had similar clinical and angiographic characteristics. The stenting procedure was highly successful in the 2 groups (95.9% and 97.4%, respectively) with similar immediate angiographic results and short-term (in-hospital) clinical event rates. At 1-year follow-up, compared with BMSs, patients with unstable angina treated with SESs had significantly lower rates of target lesion revascularization (5.5% vs 22.3%, p <0.0001), target vessel failure (10.9% vs 26.3%, p <0.0001), and major adverse cardiac events (8.4% vs 24.8%, p <0.0001). Stent thrombosis was a rare event, with only 1 patient (0.4%) in each group during the first 30 days. Late thrombosis occurred in 2 patients (0.7%) in the BMS group but in none of the SES group. In conclusion, in the higher risk subgroup of patients with unstable angina, SESs are as safe as BMSs in decreasing restenosis and the need for repeat revascularization. This is reflected by a significant decrease in major adverse cardiac events and target vessel failure. Patients with unstable angina undergoing percutaneous coronary intervention who meet the entry criteria of the SIRIUS study should be preferentially treated with SESs.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Angiography; Coronary Restenosis; Double-Blind Method; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Retreatment; Retrospective Studies; Safety; Sirolimus; Stents; Survival Rate; Ticlopidine; Time Factors; Treatment Outcome

The ZoMaxx Coronary Stent System elutes the antiproliferative agent zotarolimus via a biocompatible phosphorylcholine polymer loaded onto a novel, thin, stainless steel stent platform containing an 0.0007-inch inner layer of tantalum that enhances fluoroscopic radiopacity. The objective of this single-arm prospective clinical trial was to assess the safety and performance of the ZoMaxx stent for the treatment of coronary artery stenosis. Forty consecutive patients with ischemic coronary occlusive disease due to single de novo obstructive lesions of native coronary arteries were treated with 3 x 18 mm ZoMaxx stents at the Dante Pazzanese de Cardiologie in Saõ Paulo, Brazil, between April and July 2005. Independent core laboratories analyzed quantitative coronary angiography and intravascular ultrasound results immediately after stent implantation, and after 4 months. The lesion, procedure, and device-deployment success rates were all 100% (40 of 40). There were no major adverse cardiac events during the study. Follow-up quantitative coronary angiography at 4 months revealed in-stent and in-segment late lumen losses of 0.20 +/- 0.35 and 0.17 +/- 0.35 mm, respectively. Follow-up intravascular ultrasound at 4 months revealed 6.5 +/- 6.2% neointimal volume obstruction. There were no instances of late acquired stent incomplete apposition or stent thrombosis. In conclusion, the ZoMaxx Coronary Stent can be safely implanted for the treatment of de novo coronary artery stenosis. The inhibition of neointima formation as measured by follow-up angiography and IVUS after 4 months suggests therapeutic potential for the reduction of restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coronary Angiography; Coronary Circulation; Coronary Restenosis; Coronary Stenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phosphorylcholine; Prospective Studies; Prosthesis Design; Research Design; Sirolimus; Stents; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Although long-term follow-up after sirolimus-eluting stent implantation shows a sustained clinical benefit in several randomized and registered trials, little is known about the pattern of neointimal growth beyond the first 6 to 9 months. In this study, we therefore evaluated the possible delayed restenosis in patients with coronary artery disease treated with sirolimus-eluting stent.. A total of consecutive 333 patients with 453 lesions were enrolled in this study (among 782 consecutive patients with 1023 lesions). Lesions were subjected to follow-up by quantitative coronary angiography, and patients were divided into two groups according to the time of follow-up by quantitative coronary angiography: early group (< or =270 days, n=270 with 369 lesions) and late group (>270 days, n=63 with 84 lesions). Binary restenosis was defined as stenosis of more than 50% of the lumen diameter in the target lesion.. Baseline clinical, demographic or angiographic characteristics were well balanced between the two groups. The in-stent restenosis rate was not significant between the early group and the late group (3.5 vs. 6.0%; P>0.05). The late loss and target lesion revascularization appeared higher in late group but there were no significant differences (0.15+/-0.38 mm vs. 0.24+/-0.44 mm; and 4.9 vs. 9.5%, P>0.05, respectively). Similarly, overall thrombosis rate was also same in both groups. In-segment restenosis was, however, higher in late group compared with that in early group (7.9 vs. 16.7%, P=0.013).. In this unrestricted population, the beneficial effects of sirolimus-eluting stent implantation extend out more than 1 year in real world practice, that has been confirmed by the results of the large randomized clinical trials. The late in-segment restenosis could, however, be found, suggesting that a prolonged clinical and angiographic surveillance in this subset of patients seems to be warranted.

Topics: Aged; Aged, 80 and over; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Delayed-Action Preparations; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies; Sirolimus; Stents; Treatment Outcome

Sirolimus stent implantation has been demonstrated to be safe and effective in diabetics; however, the long-term outcomes in this high-risk population remain unknown. The aim of this study was to determine the long-term safety and efficacy of the sirolimus-eluting stent (SES) when compared with the bare metal stent (BMS) in patients included in the DIABETES (DIABETes and sirolimus Eluting Stent) trial.. The prospective multicentre DIABETES trial randomized 160 diabetic patients with one or more significant coronary stenoses in one, two, or three vessels to either SES or BMS implantation. One-year dual antiplatelet therapy (aspirin plus clopidogrel) was routinely prescribed. Clinical follow-up was scheduled at 1, 9, 12, and 13 months and 2 years. Baseline clinical and angiographic characteristics were comparable between groups. At 2 years, the rate of target lesion revascularization was significantly lower in the SES group compared with the BMS group (7.7 vs. 35.0%, P < 0.001). However, the total revascularization rate at 2 years increased in both groups due to progression of atherosclerosis in coronary segments remote from the target lesion (rate of atherosclerosis progression: 7.7% in SES group vs. 10% in BMS group; P = 0.7). During dual antiplatelet treatment (1 year), there was no stent thrombosis in the SES group, whereas two patients presented it in the BMS group. However, after clopidogrel withdrawal, three patients allocated to the SES group presented stent thromboses vs. none in the BMS group.. SES implantation in diabetic patients remains effective at 2-year follow-up. However, clinical efficacy appeared to be reduced by the occurrence of stent thrombosis between 1 and 2 years.

Topics: Aged; Aspirin; Blood Vessel Prosthesis; Clopidogrel; Coronary Restenosis; Coronary Stenosis; Death, Sudden, Cardiac; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Failure; Reoperation; Sirolimus; Ticlopidine; Treatment Outcome

To compare polytetrafluoroethylene stent graft (PTFE) with sirolimus and bare metal stents in reducing in-stent restenosis in native coronary vessels in patients with acute coronary syndrome.. The study included patients who underwent stent implantation in acute coronary syndrome from January 2003 to May 2004. The patients (n=119) were randomized either to stent graft group (n=40), sirolimus eluting stent group (n=39), or bare metal stent group (n=40). The main outcome measure of the study was the incidence restenosis at 6-month. The secondary outcome was 6-month major adverse coronary event rate.. The incidence of 6-month major adverse coronary events was similar in all three groups (8 events in stent graft, 9 in sirolimus eluting stent, and 16 in bare metal stent group events). The target lesion revascularization was higher in the bare metal stent group (P=0.044). Restenosis rate, at six-month follow-up was higher in the bare metal stent group compared with the stent graft and sirolimus eluting stent groups. The percent diameter stenosis in the follow-up was significantly higher in the bare metal stent group (P=0.005). The late loss was significantly lower in the sirolimus eluting stent group (mean+/-standard deviation, 0.2+/-0.5 mm), compared with the bare metal stent group (0.7+/-0.7 mm, P=0.034). There was a trend of lower late loss in the stent graft group than in the bare metal stent group.. Three groups of stents implanted in patients with acute coronary syndrome did not differ in the incidence of major adverse cardiac events. Sirolimus-eluting stents had a lower incidence of in-stent restenosis than bare metal stent group. Stent graft implanted in native coronary arteries appears to be safe and efficient in patients with acute coronary syndrome, but a significant reduction in in-stent restenosis was not achieved.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Female; Humans; Male; Metals; Middle Aged; Myocardial Infarction; Polytetrafluoroethylene; Sirolimus; Stents

Despite encouraging results from randomized trials, concerns exist about long-term results of sirolimus-eluting stent implantation. We sought to determine whether in-stent restenosis occurring >1 year ("late") after sirolimus-eluting stent implantation is a real clinical entity. We analyzed data on all sirolimus-eluting stents implanted in our institution before March 2003. During the study period 928 lesions in 433 patients were treated. Angiographic follow-up was performed in 306 patients (70.6%) with 679 lesions (73.2%). Angiography after 1 year was performed only in symptomatic patients. We considered restenosis "early" if it occurred during the first year and late if after 1 year. Late restenosis required demonstration of a widely patent stent at 6 to 9 months, with repeat angiography after 1 year demonstrating restenosis. Restenosis occurred in 160 lesions overall (23.5%). Of the 31 (4.6%) that were documented after 1 year, 13 were excluded from analysis due to absence of 6- to 9-month angiography; the remaining 18 (2.6%, 1.7 to 4.2) fulfilled our criteria for late restenosis (median time of documentation 607 days, interquartile range 511 to 923). In conclusion, late restenosis is an infrequent but real entity; its existence implies we should not discount the possibility of restenosis as the cause of symptoms that develop >1 year after sirolimus-eluting stent implantation.

Topics: Aged; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications; Sirolimus; Stents; Time Factors

We sought to investigate whether the previously reported midterm clinical benefit of planned sirolimus-eluting stent (SES) implantation in patients with ST-segment elevation myocardial infarction (STEMI) was maintained over a 24-month time period. Moreover, the distribution of clinical events in relation to thienopyridine discontinuation was thoroughly investigated.. No randomized data are currently available on the safety/benefit profile of SES in this subset of patients beyond 12 months.. Between March 2003 and April 2004, 175 patients with STEMI were randomly allocated to tirofiban infusion followed by SES or abciximab plus bare-metal stent (BMS). Complete follow-up information up to 720 days was available for all patients.. The cumulative incidence of death, myocardial infarction (MI), or target vessel revascularization (TVR) remained lower in the tirofiban-SES compared with the abciximab-BMS group at 2 years (24.2% vs. 38.6%, respectively; hazard ratio [HR] 0.56 [95% confidence interval (CI) 0.33 to 0.98]; p = 0.038). The composite of death/MI was similar in the tirofiban-SES (16.1%) and the abciximab-BMS groups (20.5%, HR 0.77 [95% CI 0.38 to 1.55]; p = 0.43) while the need for TVR was markedly reduced (9.8% vs. 25.5%, respectively; HR 0.34 [95% CI 0.16 to 0.77]; p = 0.01) in the tirofiban-SES arm. The rate of confirmed, probable, or possible stent thrombosis did not differ in the 2 groups, nor the incidence of death/MI after thienopyridine discontinuation.. The midterm clinical benefit of planned SES implantation assisted by tirofiban infusion in STEMI patients was mainly carried over after 2 years with no overall excess of late adverse events after thienopyridine discontinuation.

Topics: Abciximab; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Combined Modality Therapy; Coronary Restenosis; Disease-Free Survival; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Prosthesis Design; Risk; Sirolimus; Stents; Tirofiban; Tyrosine

Using serial intravascular ultrasound (IVUS), the efficacy of reduced-dose sirolimus-eluting stents (SESs) in the prevention of neointimal hyperplasia (NH) and maintenance of luminal patency in human coronary arteries was evaluated.. In the animal model, a broad therapeutic window regarding sirolimus doses in suppressing NH has been reported.. Serial cross-sectional and volumetric IVUS analyses were performed in 44 patients treated with SES that contained lower sirolimus doses (either 45% or 70%) than standard SES. For cross-sectional analysis, minimum lumen area (MLA) was measured. Percent (%) NH volumetric obstruction was calculated as 100 x NH volume/stent volume.. IVUS measurements were similar between the two drug-dose groups. At 12 months follow-up, only one case developed late incomplete stent apposition. Between 4 and 12 months, a slight increase of in-stent % area loss and % NH obstruction was noted (3.5% +/- 10.4% to 6.7% +/- 10.7% and 1.9% +/- 5.0% to 4.4% +/- 8.0%, respectively). The majority of studied cases, however, sustained less than a 10% volumetric (93% of studied cases) and area loss (75% of studied cases) in the stented segment up to 12 months. At 12 months, % area loss within the stented segments and 5-mm reference segments were comparable (7.0% +/- 19.6% versus 6.7% +/- 10.7%).. Although slight increases of NH were noted, SESs, delivering two reduced drug doses, appeared to be effective for maintaining luminal patency during 12 months follow-up.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Dose-Response Relationship, Drug; Drug-Eluting Stents; Humans; Hyperplasia; Sirolimus; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional; Vascular Patency

We sought to provide long-term follow-up data of sirolimus-eluting stents (SES) versus bare-metal stents (BMS) in saphenous vein grafts (SVG) from the RRISC (Reduction of Restenosis In Saphenous vein grafts with Cypher) trial.. We have previously shown that, in SVG, the use of SES reduces 6-month restenosis and repeated revascularization procedures versus the use of BMS. These data are consistent with trials in native coronary arteries. However, recently published long-term follow-up data of these trials have revealed an increased risk of adverse events (particularly very late stent thrombosis) after SES.. A total of 75 patients with 96 SVG lesions were randomized to SES versus BMS. All patients underwent clinical follow-up up to 3 years. Specific outcomes assessed in this secondary post-hoc analysis were all-cause mortality, myocardial infarction, and target vessel revascularization.. Thirty-eight patients received 60 SES for 47 lesions, whereas 37 patients received 54 BMS for 49 lesions. At a median follow-up time of 32 months (interquartile range 26.5 to 36 months), 11 deaths (7 cardiac, of which 1 was caused by very late stent thrombosis and, 3 were sudden) occurred after SES (29% [95% confidence interval (CI) 17% to 45%]) versus 0 after BMS (0% [95% CI 0% to 9%]) with an absolute difference of 29% ([95% CI 14% to 45%], p < 0.001). The rates of myocardial infarction and target vessel revascularization were not different: 18% and 34% after SES, respectively, versus 5% and 38% after BMS, respectively (p = 0.15 and p = 0.74, respectively).. In this secondary post-hoc analysis, BMS were associated with lower long-term mortality than SES for SVG disease. Also, the 6-month reduction in repeated revascularization procedures with SES was lost at longer-term follow-up. (RRISC Study: Reduction of Restenosis In Saphenous Vein Grafts With Cypher Sirolimus-Eluting Stent; http://clinicaltrials.gov/ct/show/NCT00263263?order=1; NCT00263263).

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Confidence Intervals; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Coronary Stenosis; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Graft Rejection; Humans; Male; Metals; Probability; Prosthesis Design; Retreatment; Risk Assessment; Saphenous Vein; Sirolimus; Statistics, Nonparametric; Stents; Survival Rate; Time Factors; Treatment Outcome

Long-term results of recent landmark trials document both benefits and risks of drug-eluting stents (DES) for coronary revascularization. Interestingly, the conclusions drawn from these data vary widely since significant differences in DES penetration rates become obvious when the utilization of this technology is compared between hospitals or even countries. Based on the recommendations of the European Society of Cardiology, the FDA as well as data derived from the BASKET-LATE study, we propose that a maximum penetration rate of 50% for DES seems appropriate at present. Analysis of the length/diameter distribution combined with the use of validated restenosis reference charts allows identification of high-risk patients regarding restenosis risk and modeling the use of DES depending on financial resources and clinical indication. Such algorithm provides the rational for preprocedural risk stratification and efficient use of resources.

Topics: Coronary Artery Disease; Coronary Restenosis; Cost-Benefit Analysis; Drug Administration Routes; Female; Humans; Immunosuppressive Agents; Male; Paclitaxel; Sirolimus; Stents

The time course of neointimal formation after stent implantation has not been studied extensively by angioscopy in the drug-eluting stent era.. Serial angioscopic findings at first follow-up (3.6+/-1.1 months), second follow-up (10.5+/-1.6 months), and third follow-up (21.2+/-2.2 months) after stent implantation were compared between sirolimus-eluting stents (SES, n=17) and bare-metal stents (BMS, n=11). Neointimal coverage, thrombus, and presence of yellow plaques underneath the stents were assessed. Neointimal coverage was graded as follows: grade 0, stent struts were fully visible; grade 1, struts bulged into the lumen, although they were covered; grade 2, struts were embedded by the neointima but were seen translucently; or grade 3, struts were fully embedded and invisible. Neointimal coverage was remarkably different between SES and BMS at each follow-up point. Neointimal coverage grade was 1.1+/-0.5 in SES versus 2.9+/-0.3 in BMS at the first follow-up (P<0.0001), 1.1+/-0.5 in SES versus 3.0+/-0.0 in BMS (P<0.0001) at the second follow-up, and 1.3+/-0.5 in SES versus 3.0+/-0.0 in BMS at the third follow-up (P=0.0009). No significant serial changes in coverage grade were noted in the BMS group, whereas coverage grade slightly but significantly increased at the third follow-up in the SES group (P<0.05). Thrombi were detected in 4 SES: a red thrombus was seen from the first to the third follow-up in 2; another was detected only at the third follow-up; and the fourth was seen at the first follow-up but disappeared at the second follow-up, associated with a new white thrombus despite dual antiplatelet therapy. Yellow plaques had disappeared by the time of the second follow-up in BMS. In contrast, yellow plaques were exposed in 71% of SES at the first follow-up and remained exposed until the third follow-up. Neointimal coverage grades correlated with thrombi (P=0.002) and with yellow plaques (P<0.0001).. Serial angioscopic findings up to 2 years after SES implantation were markedly different from those after BMS. Neointimal coverage was completed by 3 to 6 months in BMS. In contrast, SES demonstrated the presence of thrombi and yellow plaques even as much as 2 years after implantation.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Metals; Middle Aged; Platelet Aggregation Inhibitors; Sirolimus; Stents; Tunica Intima

The aims of this study were to assess (i) the feasibility, safety and efficacy of sirolimus-eluting stents (SESs) in treating in-stent restenosis (ISR), (ii) the risk factors for recurrent ISR, and (iii) the long-term major adverse cardiac events (MACE).. Between May 2002 and April 2004, 100 consecutive patients with evidence of myocardial ischaemia and 112 ISRs in native coronary arteries were treated using SESs. We evaluated the rate of procedural and clinical success, the incidence of in-hospital and long-term MACE, the recurrence rate of ISR after 6-8 months, and the risk factors for recurrent ISR and follow-up MACE.. Forty-five percent of the lesions were directly stented. After stent implantation, the minimal lumen diameter increased from 0.51 +/- 0.32 to 2.50 +/- 0.32 mm in the stents and to 2.30 +/- 0.35 mm in the lesions (acute gain 1.99 +/- 0.37 mm). The procedural success rate was 99%. The clinical success rate was 88%. MACE occurred in 2.0% of patients during hospitalisation and in 12.8% after a median follow-up of 15.1 months (interquartile range 8.4-19.7). The recurrence rate of ISR was 11.8% after a median follow-up of 7.7 months (interquartile range 7.4-8.4). The risk for recurrent ISR was significantly higher in patients with diabetes or hypertension, in those aged more than 65 years and in female patients, as well as in the lesions with a small minimal lumen diameter. Three-vessel disease and age were risk factors for MACE.. This study confirms the feasibility, safety and effectiveness of using SESs to treat ISR, and identifies a risk profile for recurrent ISR and MACE.

Topics: Coronary Restenosis; Drug Delivery Systems; Feasibility Studies; Female; Follow-Up Studies; Heart Diseases; Humans; Immunosuppressive Agents; Male; Middle Aged; Risk Factors; Sirolimus; Stents; Treatment Outcome

Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy Driver stents (ZES) demonstrated significant reductions in target lesion revascularization rate with few apparent adverse events compared with bare metal stents (BMS; uncoated Driver stents) in a prospective, multicenter, double-blind, randomized controlled trial in de novo coronary lesions. The aim of this study was to examine detailed vascular responses to ZES compared with BMS using serial intravascular ultrasound analysis. A total of 343 patients (ZES n = 178, BMS n = 165) were enrolled in this formal, prespecified intravascular ultrasound substudy of the Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE Zotarolimus-Eluting Driver Coronary Stent in de Novo Native Coronary Artery Lesions (ENDEAVOR II), a prospective, multicenter, double-blind, randomized controlled trial to compare ZES and BMS in de novo native coronary artery lesions. Quantitative and qualitative intravascular ultrasound analyses were performed postprocedurally and at 8-month follow-up in stented and reference segments. ZES showed significantly less neointima, with a larger lumen than BMS at 8 months (percentage neointimal volume 17.6 +/- 10.1% vs 29.4 +/- 17.2%, p <0.0001; maximum percentage neointimal area 32.9 +/- 13.0% vs 47.6 +/- 18.6%, p <0.0001; minimum luminal area 4.9 +/- 1.6 vs 4.0 +/- 1.7 mm(2), p <0.0001) and no unfavorable edge effect. In the 18-mm single stents, ZES showed evenly inhibited neointima compared with BMS. Neither persistent stent-edge dissection nor late-acquired incomplete stent apposition was observed in either group. In conclusion, ZES showed evenly inhibited neointima with no apparent adverse vascular response in stented and reference segments at 8 months compared with BMS.

Topics: Chromium Alloys; Coated Materials, Biocompatible; Cohort Studies; Coronary Artery Disease; Coronary Restenosis; Double-Blind Method; Endosonography; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Phosphorylcholine; Prospective Studies; Sirolimus; Stents; Tunica Intima

Recent evidence shows that drug-eluting stent devices (DES) substantially reduce the risk of in-stent restenosis compared with classic bare metal stent devices (BMS). In Belgium, however, the use of BMS is still standard procedure due to the higher prices of the newer DES. Although the use of DES is more expensive in the short term it might be beneficial in the long term due to the avoidance of revascularization costs. The primary objective of this study is to compare the net cost of DES and BMS from the perspective of Belgian health care.. Cost differences between DES and BMS are determined by the difference in stent price and the difference in the rate of re-intervention. The cost of revascularization of patients with in-stent restenosis was estimated based on data gathered at the Antwerp University hospital (UZA). Data on effectiveness were obtained from a literature meta-analysis. Because of some important study limitations, a sensitivity analysis was included in this study. In general, the use of DES was cost saving as compared with BMS, with savings amounting to E 165 for Cypher stent devices and Euro 128 for Taxus stent devices in the base case scenario. For patients with a high risk of restenosis net savings persist in almost all sensitivity analyses.. The use of DES in patients with a high in-stent restenosis risk is cost saving. Price evolutions in the stent device market predict that the use of DES, if not yet cost saving, will become cost saving in the near future for all types of patients. Recent evidence, however, casts some doubt on the long-term effectiveness of DES.

Topics: Angioplasty, Balloon, Coronary; Belgium; Coronary Artery Bypass; Coronary Restenosis; Cost-Benefit Analysis; Drug-Eluting Stents; Follow-Up Studies; Humans; Metals; Paclitaxel; Prosthesis Design; Reoperation; Research Design; Retrospective Studies; Sensitivity and Specificity; Sirolimus; Treatment Outcome

Percutaneous coronary intervention (PCI) has been increasingly employed to treat unprotected left main coronary artery (LMCA) stenosis, with variable success. This strategy has been applied to patients undergoing drug-eluting stent (DES) implantation for unprotected LMCA stenosis.. From April 2003 to June 2006, 114 consecutive patients with de novo unprotected LMCA stenosis underwent PCI with DES, and were followed over a mean period of 17.1 +/- 9.1 months. The primary endpoint of the study was the occurrence of major adverse cardiovascular events (MACE) (cardiac death, myocardial infarction [MI] or target lesion revascularization [TLR]).. LMCA stenting was successfully performed in all patients. In-hospital mortality was 3.5%, with no in-hospital non-fatal MI or emergency coronary artery bypass grafts. During the follow-up period, the all-cause mortality rate was 7.9%, with 3.5% cardiac-related deaths. TLR was performed in 7.9% of patients, and the MACE rate was 14.9%. All non-surviving patients were at high surgical risk (EuroSCORE > 6) and had a significantly higher EuroSCORE than surviving patients that patients with a EuroSCORE < or = 11 had significantly improved survival rates over those with a EuroSCORE > 11 (p < 0.0001). Moreover, most of the patients who died of cardiac causes were diabetic (71.4% vs. 26.6%; p < 0.05). Acute coronary syndromes, as clinical presentation, and non-ostial LMCA disease were also significantly more common within non-surviving patients (100% vs. 67%; p < 0.05, and 92.3% vs. 66.3%; p = 0.05, respectively).. Stenting of unprotected LMCA appears to be associated with a favorable mid-term outlook, especially in selected patients.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Paclitaxel; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; Sirolimus; Stents; Survival Rate; Treatment Outcome

We assessed the impact of vessel size on angiographic and long-term clinical outcome after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) within a randomized trial (SIRTAX [Sirolimus-Eluting Stent Compared With Paclitaxel-Eluting Stent for Coronary Revascularization]).. Percutaneous coronary intervention in small-vessel disease is associated with an increased risk of major adverse cardiac events (MACE).. A total of 1,012 patients were randomly assigned to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of angiographic and clinical outcome was performed up to 2 years after PCI according to size of the treated vessel (reference vessel diameter < or =2.75 vs. >2.75 mm).. Of 1,012 patients, 370 patients (37%) with 495 lesions underwent stent implantation in small vessels only, 504 patients (50%) with 613 lesions in large vessels only, and 138 patients (14%) with 301 lesions in both small and large vessels (mixed). In patients with small-vessel stents, SES reduced MACE by 55% (10.4% vs. 21.4%; p = 0.004), mainly driven by a 69% reduction of target lesion revascularization (TLR) (6.0% vs. 17.7%; p = 0.001) compared with PES at 2 years. In patients with large- and mixed-vessel stents, rates of MACE (large: 10.4% vs. 13.1%; p = 0.33; mixed: 16.7% vs. 18.0%; p = 0.83) and TLR (large: 6.9% vs. 8.6%; p = 0.47; mixed: 16.7% vs. 15.4%; p = 0.86) were similar for SES and PES. There were no significant differences with respect to death and myocardial infarction between the 3 groups.. Compared with PES, SES more effectively reduced MACE and TLR in small-vessel disease. Differences between SES and PES appear less pronounced in patients with large- and mixed-vessel disease. (The SIRTAX trial; http://clinicaltrials.gov/ct/show/NCT00297661?order=1; NCT00297661).

Topics: Aged; Angioplasty, Balloon, Coronary; Confidence Intervals; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Male; Paclitaxel; Probability; Proportional Hazards Models; Prospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Treatment Outcome

To assess the safety and efficacy of direct stenting using the sirolimus-eluting BX Velocitytrade mark stent in patients with coronary lesions.. Although direct coronary stenting has become a widespread practice, there have been no systematic assessments of direct stenting with drug-eluting stents.. Total of 225 patients with identical inclusion and exclusion criteria as the original SIRIUS trial were enrolled in this prospective single-arm study. They were compared in a no-inferiority design with 412 similar patients from the SIRIUS trial who had sirolimus-eluting stents deployed after predilatation and were preassigned to angiographic follow-up evaluation.. Direct stenting was successful in 85.8% of the patients. Compared with the predilatation group, direct stenting was associated with shorter median procedure duration (33 min vs. 45 min, P < 0.001). Angiographic follow-up at 8 months revealed similar late loss (in-stent-0.19 +/- 0.47 mm vs. 0.17 +/- 0.44 mm, and in-lesion-0.23 +/- 0.41 mm vs. 0.24 +/- 0.47 mm) and similar frequency of binary restenosis (in-stent-4.6% vs. 3.2% and in-lesion-6.1% vs. 8.9%) between the two treatment strategies. However, stent-edge restenosis was lower with direct stenting than in the predilatation control group (2.1% vs. 6.9%, P = 0.02). At 12-months, there were no significant differences in target lesion revascularization (3.7% vs. 5.1%, P = ns) or composite major adverse cardiac events (7.0% vs. 8.3%, P = ns).. In patients similar to those treated in the SIRIUS trial, direct stenting using sirolimus-eluting stents achieves excellent short- and long-term clinical and angiographic results with shorter procedure time and less frequent stent edge restenosis compared with predilation stent implantation techniques.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Male; Middle Aged; Prospective Studies; Research Design; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional; United States

This study examined the clinical outcomes at 5 years in RAVEL (A Randomized Comparison of a Sirolimus-Eluting Stent With a Standard Stent for Coronary Revascularization), the first controlled trial of drug-eluting stents.. The 6-month rate of angiographic coronary restenosis has been markedly lowered by sirolimus-eluting stents (SES). The long-term performance of drug-eluting stents, however, is under close scrutiny.. The trial included 238 patients (mean age 60.7 +/- 10.4 years, 76% men) with a single, de novo native coronary artery lesion, randomly assigned to treatment with SES versus bare-metal stents (BMS). Rates of major adverse cardiac events (MACE), defined as all-cause mortality, myocardial infarction, and percutaneous or surgical revascularization up to 5 years of follow-up, and rates of stent thrombosis were compared between the 2 treatment groups.. Complete datasets were available in 92.5% of patients treated with SES and 89.1% of patients assigned to BMS. The 1-, 3-, and 5-year rates of survival free from target lesion revascularization (TLR) were, respectively, 99.2%, 93.8%, and 89.7% in the SES group versus 75.9%, 75.0%, and 74.0% in the control group (p < 0.001; log-rank). Rates of all MACE at 5 years were 25.8% in patients treated with SES versus 35.2% in patients assigned to BMS (p = 0.03; log-rank). Rates of stent thrombosis, per protocol or by the Academic Research Consortium definitions, were similar in both groups.. The 5-year rate of TLR associated with SES was significantly lower than that with BMS. There was no apparent adverse effect associated with the use of SES, although the trial was not powered to examine uncommon complications.

Topics: Aged; Aged, 80 and over; Blood Vessel Prosthesis; Coronary Restenosis; Coronary Stenosis; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Outcome Assessment, Health Care; Sirolimus; Stents; Survival Analysis; Treatment Outcome

Although the increased utilization of drug-eluting stents is well supported by multiple studies with clinical trial data for many patient and lesion subsets, their use to treat diseased saphenous vein graft (SVG) lesions is much less well substantiated. We sought to ascertain and compare 12-month target vessel revascularization (TVR) rates for sirolimus-eluting Cyphertrade mark stents and bare-metal stents (BMS) when utilized to treat stenoses in diseased SVGs.. Therefore, we conducted a multicenter matched-control study in patients treated for de novo SVG lesions with Cypher or BMS, matching for reference vessel diameter, stent length, diabetes and number of stents utilized. The primary study endpoint was TVR at 12 months.. Three hundred and fifty patients were matched, with patient age = 69 +/- 9 years, 77% male, 39% diabetics, SVG age = 119 +/- 75 months, reference vessel diameter = 3.3 +/- 0.4 mm, target lesion length = 17.4 +/- 8.4 mm (p = NS for all between-group comparisons). Twelve-month TVR was modestly reduced with Cypher stenting (6.8% vs. 11.8%; p = 0.14) due to a trend toward a reduction in binary restenosis (7.4% vs. 13.6%; p = 0.08). Twelve-month survival was 95.3% and 96.4% in the Cypher and BMS groups, respectively (p = 0.79).. Cypher stents appear to modestly reduce TVR without apparent safety risk compared with BMS when applied to the treatment of diseased SVGs. In conjunction with other available studies, these data support Cypher stent use in this setting.

Topics: Aged; Angioplasty, Balloon, Coronary; Case-Control Studies; Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications; Saphenous Vein; Sirolimus; Treatment Outcome

This prospective, randomized study sought to directly compare the performance of paclitaxel and rapamycin on an otherwise identical, polymer-coated drug-eluting stent (DES) platform.. Stents with identical design and biodegradable polymeric coating that elute either rapamycin or paclitaxel over a 2 months time period were utilized. In this pilot trial that included 91 patients, both stent platforms proved safe with no case of death, Q-wave myocardial infarction or stent thrombosis within a 9 months follow-up period. Late-lumen loss was markedly greater in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group (0.96 +/- 0.75 vs. 0.33 +/- 0.46 mm, P < 0.0001). Likewise, the rate of angiographic restenosis was higher in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group [39.0 vs. 12.2%; relative risk (RR) 3.20 (95% confidence interval, 1.29-7.92), P = 0.005]. Concomitantly, the need for target lesion revascularization was higher in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group [26.7 vs. 8.7%; RR 3.07 (1.07-8.80), P = 0.02].. The results of this clinical trial that is the first to directly compare the performance of paclitaxel and rapamycin on a DES platform otherwise identical in design and polymeric coating imply that rapamycin is more effective for the prevention of coronary restenosis on a DES platform with mid-term drug release and less dependent on release kinetics than paclitaxel. Thus, to ensure efficacy, drug release from a paclitaxel-coating stent platform must be prolonged and well controlled to achieve results that are comparable with the FDA-approved paclitaxel-eluting stent platform.

Topics: Absorbable Implants; Adult; Aged; Coronary Angiography; Coronary Restenosis; Drug Combinations; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Prospective Studies; Sirolimus; Treatment Outcome; Tubulin Modulators

This study sought to analyze the effectiveness of drug-eluting stents in a high-risk group of diabetic patients. Previously, this had been analyzed only in substudies of larger trials or in clinical investigations enrolling a small number of patients.. Drug-eluting stents are highly effective in reducing the rate of in-stent restenosis.. Two hundred patients with diabetes and de novo coronary artery lesions were enrolled in 16 centers: 98 were randomly assigned to sirolimus-eluting stents (SES) and 102 received bare-metal stents (BMS). The primary end point was in-segment late luminal loss. Major adverse cardiac events (MACE) rate was analyzed at 30 days and 8 and 12 months.. The extent of in-segment late luminal loss in the SES group was 0.18 mm compared with 0.74 mm in the BMS group. In-segment restenosis was identified on follow-up angiography in 8.8% of the patients in SES and in 42.1% in BMS (p < 0.0001). Target lesion revascularization was performed in 5.3% of the patients in SES and in 21.1% of the patients in BMS (p = 0.002). The SES was effective in the treatment group with oral diabetic medication as well as in the insulin-dependent treatment group (3.6% SES vs. 38.8% BMS). There was no subacute stent thrombosis in the SES group up to 1 year. The MACE rate was not significantly different at 30 days. At 12 months, MACE rate was 14.7% in SES versus 35.8% in BMS.. The SES is safe and highly effective in patients with diabetes mellitus and coronary artery disease and associated with a significant decrease in the extent of late luminal loss.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Drug Delivery Systems; Female; Follow-Up Studies; Germany; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Sirolimus; Stents; Thrombosis; Treatment Outcome

The clinical and angiographic factors that predict clinically driven target lesion revascularization (TLR) in patients treated with the zotarolimus-eluting stent (ZES) are not known. Accordingly, the differences between ZES-treated patients who required TLR and ZES-treated patients who did not require TLR were examined in 1,306 patients enrolled in 4 pivotal trials of the Endeavor ZES (Medtronic Vascular, Santa Rosa, CA) for the treatment of symptomatic native coronary artery disease. TLR was performed in 64 patients (4.9%) by 9 months, with most cases (89.1%) occurring after 30 days. ZES-treated patients who required TLR had a greater incidence of 2- or 3-vessel disease (p <0.01), more stents implanted (p = 0.05), and lower device (p = 0.04) and procedure (p <0.01) success rates than ZES-treated patients who did not require TLR. The stents implanted in ZES-treated patients who later required TLR were also longer (p = 0.02) and smaller in diameter (p <0.01). Most angiographic outcomes at 8 months (12 months for ZES-treated patients in ENDEAVOR I) were worse for ZES-treated patients who later required TLR. At 9 months, 10.9% of the ZES-treated patients who required TLR had had myocardial infarctions, compared with 2.2% who did not require TLR (p = 0.001). Multivariate analysis identified older age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00-1.06), male sex (OR, 1.79; 95% CI, 0.88-3.65), and longer lesion length (OR, 1.03; 95% CI, 0.99-1.07) as risk factors for TLR after ZES implantation (with a C statistic of 0.61, suggesting a modest discriminatory value). These data provide insight into the clinical and angiographic factors that predict TLR at 9 months in ZES-treated patients, making possible the focused surveillance of selected ZES-treated patients who might be at greater risk of TLR.

Topics: Anti-Bacterial Agents; Coronary Angiography; Coronary Disease; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Registries; Sirolimus

The intravascular ultrasound (IVUS) findings during repeat intervention for drug-eluting stent (DES) restenosis have not been well described.. We identified 62 consecutive DES restenosis lesions (45 sirolimus-eluting stents and 17 paclitaxel-eluting stents) undergoing repeat intervention with pre and postintervention IVUS. Lumen, stent and intimal hyperplasia (stent minus lumen) areas were measured at the minimal lumen area (MLA) site and minimal stent area (MSA) site.. Repeat stent implantation was performed in 55 lesions (88.7%). Overall, MLA increased from 2.3 +/- 0.7 mm(2) preintervention to 4.6 +/- 1.6 mm(2) postintervention. Preintervention MLA was seen at exactly the preintervention MSA site in 42%, while 73% of postintervention MLAs were located at the preintervention MSA site. There was a strong correlation between the preintervention MSA and the postintervention MLA (r = 0.79; p < 0.001). Preintervention MSA was the strongest independent predictor of a larger postintervention MLA (coefficient 0.72; p < 0.001).. The preintervention MSA was a major predictor of larger lumen area after repeat intervention for DES restenosis. Several IVUS studies have shown that stent dimensions do not change over time. Therefore, the MSA of the original stent implantation procedure still has the greatest impact on subsequent interventions to treat DES restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Ultrasonography, Interventional

Sirolimus-eluting stents (SESs) were recently shown to be superior to vascular brachytherapy for the treatment of restenosis within a bare metal stent. No economic comparison of these alternative strategies has yet been reported.. We conducted a prospective health economic study involving all patients randomized to SES (n = 259) or brachytherapy (n = 125) in the SISR trial. Procedural, hospital, and outpatient costs, as well as physician fees, were estimated through 12 months based on measured resource use and itemized hospital bills. Cost-effectiveness was assessed in terms of the cost per repeat revascularization avoided, cost per major adverse cardiac event avoided, and cost per event-free patient.. Although initial device costs were approximately $1100/patient higher in the SES group, this was offset by higher physician fees associated with brachytherapy, such that initial hospitalization costs were similar for the 2 groups. Because SES significantly reduced repeat revascularization procedures and major adverse cardiac event compared with brachytherapy during follow-up, cumulative 12-month costs were significantly lower in the SES group ($16,482 vs $19,435, mean difference -$2953, 95% CI -$5470 to -$792). Sirolimus-eluting stenting was thus both more effective and less expensive than brachytherapy, as confirmed in >98% of bootstrap replications for each of the cost-effectiveness outcomes.. Compared with vascular brachytherapy, SES is an economically dominant strategy for the treatment of in-stent restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Brachytherapy; Cardiac Catheterization; Coronary Restenosis; Cost Savings; Cost-Benefit Analysis; Drug-Eluting Stents; Female; Follow-Up Studies; Health Care Costs; Health Resources; Humans; Male; Middle Aged; Sirolimus

The aim of this intravascular ultrasound (IVUS) study was to assess the efficacy of the AXXESS Plus stent system for the treatment of bifurcation coronary lesions.. The AXXESS Plus is a novel bifurcation drug-eluting stent, comprised of a self-expanding flare-shaped stent platform and bioabsorbable polymer coating that releases Biolimus A9.. Data were obtained from the AXXESS PLUS trial, a prospective, multicenter, nonrandomized, single-arm study to evaluate safety and efficacy. Six-month follow-up IVUS analysis was available in 49 cases. Volumetric analysis using Simpson's method within the AXXESS stent, and cross-sectional analysis at the ostium of main branch and/or side branch was performed. Impact of bifurcation angle on stent expansion at the carina was also evaluated.. Within the AXXESS stent, neointimal volume obstruction percentage was 2.3% +/- 2.2%, with a minimum lumen area of 7.9 +/- 2.6 mm(2). Lumen area was 5.2 +/- 1.7 mm(2) at main branch ostium, and 4.0 +/- 1.5 mm(2) at side branch ostium. In two cases, incomplete stent apposition was observed at the proximal edge of the AXXESS stent. In one case, a gap between the AXXESS stent and an additional stent was observed. Greater bifurcation angle inversely correlated with smaller stent area at side branch ostium (r = -0.54, P = 0.03) but not at main branch ostium (r = -0.2, P = 0.29).. This novel self-expanding, drug-eluting bifurcation stent demonstrated effective lesion coverage along with significant neointimal suppression equivalent to current generation balloon-expandable drug-eluting stent technology.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Hyperplasia; Male; Middle Aged; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

The GERSHWIN study (German Stent Health Outcome and Economics Within Normal Practice) was designed to evaluate long-term effects of treatment of coronary artery disease (CAD) with sirolimus-eluting stents (SES), as compared to bare-metal stents (BMS).. Within a multicenter, prospective intervention study in 35 hospitals throughout Germany, CAD patients with coronary stenosis and elective percutaneous coronary intervention (PCI) indication were treated either with SES or BMS (sequential control design with a case-to-control ratio of 2 : 1). Standardized questionnaires were completed by patients and their physicians at baseline, 3, 6, 12, and 18 months following PCI to document re-PCI for restenosis, myocardial infarction (MI), coronary bypass surgery (CABG), and death. Angiographic PCI documentation was evaluated by an independent expert.. From April 2003 until June 2005, 658 patients were treated with SES (mean age 63 +/- 9 years, 87% male) and 294 patients with BMS (mean age 64 +/- 10 years, 79% male). Significant baseline differences were found by age, gender, household status, three vessel disease, and number of implanted stents. After 18 months, 8% of the SES versus 17% of the BMS group had undergone target vessel revascularization (p adjusted < 0.0001). There were no significant differences between BMS and SES regarding MI, CABG, or death. Re-PCI of target and new non-target vessel lesions was performed at a significantly lower degree of stenosis in SES than in BMS.. Compared to patients with BMS, patients with implantation of SES experienced considerably fewer target vessel revascularizations. The threshold to perform re-PCI appeared lower in SES than in BMS. An extended evaluation of the effects of SES will be available from the 3-year follow-up of the GERSHWIN study.

Topics: Angiography; Coronary Restenosis; Delayed-Action Preparations; Female; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Risk Assessment; Risk Factors; Sirolimus; Stents; Treatment Outcome

Sirolimus- and paclitaxel-eluting stents effectively reduce restenosis in small coronary vessels. The relative efficacy of these drug-eluting stents in this high-risk subset is not known.. A total of 360 patients undergoing percutaneous coronary intervention for de novo lesions in native coronary vessels with a diameter of <2.80 mm received randomly paclitaxel-eluting stents (n=180) or sirolimus-eluting stents (n=180). The primary endpoint was in-stent late luminal loss. Secondary endpoints were angiographic restenosis and need of target lesion revascularization. The study intended to show that the paclitaxel-eluting stent is not inferior to the sirolimus-eluting stent with respect to the primary endpoint. The non-inferiority margin was set at 0.16 mm. Follow-up angiography was performed in 87% of the patients. In-stent late luminal loss in the paclitaxel-eluting stent group was 0.32 mm (upper 95% boundary, 0.42 mm), which was greater than that in the sirolimus-eluting stent group, failing to show the non-inferiority of the paclitaxel-eluting stent to the sirolimus-eluting stent (P>0.99). Angiographic restenosis was found in 19.0% of the lesions in the paclitaxel-eluting stent group and 11.4% of the lesions in the sirolimus-eluting stent group (P=0.047). Target lesion revascularization was performed in 14.7% of the lesions treated with paclitaxel-eluting stents and 6.6% of the lesions treated with sirolimus-eluting stents (P=0.008).. The paclitaxel-eluting stent is associated with a greater late luminal loss and is less effective in reducing restenosis in small coronary vessels than the sirolimus-eluting stent.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Female; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Paclitaxel; Prospective Studies; Sirolimus; Stents; Treatment Outcome

The purpose of the SCANDSTENT study was to evaluate the use of sirolimus-eluting stents (SES) in complex coronary lesions.. The use of SES improves angiographic and clinical outcomes compared with bare-metal stents (BMS) in simple coronary artery lesions, but there is limited evidence of their safety and efficacy when implanted in complex lesions.. We randomly assigned 322 patients with symptomatic complex coronary artery disease to receive either SES or BMS. The lesions were occluded (36%), bifurcational (34%), ostial (22%), or angulated (8%) in morphology. The primary end point was the difference in minimal lumen diameter six months after stent implantation.. The patients were well matched in terms of demographic and angiographic baseline characteristics; 18% had diabetes. The reference vessel diameter was 2.86 mm in mean, and the lesion length 18.0 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.48 mm compared with 1.65 mm in those who received BMS (p < 0.001), a diameter stenosis of 19.3% versus 43.8% (p < 0.001), and 2.0% versus 31.9% developed restenosis (p < 0.001). The rate of major adverse cardiac events was 4.3% with SES versus 29.3% with BMS (p < 0.001), and stent thrombosis was observed in 0.6% in the SES group versus 3.1% in the BMS group (p = 0.15).. The use of SES markedly reduced restenosis and the occurrence of major adverse cardiac events in patients with complex coronary artery lesions without increasing the risk of stent thrombosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Stents

We compared two consecutive series of patients treated with sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES).. Two hundred and ninety-five patients with 590 coronary lesions were treated with 274 SES and 379 PES. Patients with symptoms or positive dobutamine stress echocardiography were subjected to repeat coronary angiography.. During a follow-up of 13.3 +/- 5.7 months, the incidence rate of major adverse cardiac events (MACE) was 4.1%, including, 1 death, 4 Q-wave myocardial infarctions, 2 late angiographic stent thromboses, 3 subacute stent thromboses, and 11 target vessel revascularizations (TVR), and was not significantly different between SES (n = 5) and PES (n = 7). Stent overlapping was found to be an independent predictor of both MACE (odds ratio = 0.078, P = 0.02) and TVR (odds ratio = 0.077, P = 0.02). Follow-up symptoms- or ischemia-driven angiography was performed in 45 patients. Only vessel size was a predictor of stent restenosis (P = 0.02), independent of stent type. Late loss was independently predicted by postdilatation of stent (beta =-0.24, P = 0.03), but not by type of stent (P = 0.14) or other parameters. Edge restenosis was seen in 8 patients subjected to lesion predilatation. The restenosis pattern after SES implantation was focal, but diffuse (n = 1) or proliferative (n = 1) restenosis, and in-stent aneurysm formation (n = 1) was also seen with PES.. Despite a trend for a higher incidence of MACE with PES, no significant differences between the two stent types were detected. Diffuse restenosis was seen only with PES, and edge restenosis only in lesions with balloon predilatation before stent implantation. Stent overlapping was an independent predictor of both TVR and MACE.

Topics: Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Paclitaxel; Prospective Studies; Sirolimus; Stents; Treatment Outcome

Compared with bare metal stents, sirolimus-eluting and paclitaxel-eluting stents have been shown to markedly improve angiographic and clinical outcomes after percutaneous coronary revascularization, but their performance in the treatment of de novo coronary lesions has not been compared in a prospective multicenter study.. To compare the safety and efficacy of sirolimus-eluting vs paclitaxel-eluting coronary stents.. Prospective, randomized comparative trial (the REALITY trial) conducted between August 2003 and February 2004, with angiographic follow-up at 8 months and clinical follow-up at 12 months.. Ninety hospitals in Europe, Latin America, and Asia.. A total of 1386 patients (mean age, 62.6 years; 73.1% men; 28.0% with diabetes) with angina pectoris and 1 or 2 de novo lesions (2.25-3.00 mm in diameter) in native coronary arteries.. Patients were randomly assigned in a 1:1 ratio to receive a sirolimus-eluting stent (n = 701) or a paclitaxel-eluting stent (n = 685).. The primary end point was in-lesion binary restenosis (presence of a more than 50% luminal-diameter stenosis) at 8 months. Secondary end points included 1-year rates of target lesion and vessel revascularization and a composite end point of cardiac death, Q-wave or non-Q-wave myocardial infarction, coronary artery bypass graft surgery, or repeat target lesion revascularization.. In-lesion binary restenosis at 8 months occurred in 86 patients (9.6%) with a sirolimus-eluting stent vs 95 (11.1%) with a paclitaxel-eluting stent (relative risk [RR], 0.84; 95% confidence interval [CI], 0.61-1.17; P = .31). For sirolimus- vs paclitaxel-eluting stents, respectively, the mean (SD) in-stent late loss was 0.09 (0.43) mm vs 0.31 (0.44) mm (difference, -0.22 mm; 95% CI, -0.26 to -0.18 mm; P<.001), mean (SD) in-stent diameter stenosis was 23.1% (16.6%) vs 26.7% (15.8%) (difference, -3.60%; 95% CI, -5.12% to -2.08%; P<.001), and the number of major adverse cardiac events at 1 year was 73 (10.7%) vs 76 (11.4%) (RR, 0.94; 95% CI, 0.69-1.27; P = .73).. In this trial comparing sirolimus- and paclitaxel-eluting coronary stents, there were no differences in the rates of binary restenosis or major adverse cardiac events.. ClinicalTrials.gov Identifier: NCT00235092.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Implants; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Stents; Survival Analysis; Treatment Outcome

Although vascular brachytherapy is the only approved therapy for restenosis following bare-metal stent implantation, drug-eluting stents are now being used. Data on the relative merits of each are limited.. To determine the safety and efficacy of the sirolimus-eluting stent compared with vascular brachytherapy for the treatment of patients with restenosis within a bare-metal stent.. Prospective, multicenter, randomized trial of 384 patients with in-stent restenosis who were enrolled between February 2003 and July 2004 at 26 academic and community medical centers. Data presented represent all follow-up as of June 30, 2005.. Vascular brachytherapy (n = 125) or the sirolimus-eluting stent (n = 259).. Target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months postprocedure.. Baseline patient characteristics were well matched. Lesion length was similar between vascular brachytherapy and sirolimus-eluting stent patients (mean [SD], 16.76 [8.55] mm vs 17.22 [7.97] mm, respectively; P = .61). Procedural success was 99.2% (124/125) in the vascular brachytherapy group and 97.3% (250/257) in the sirolimus-eluting stent group (P = .28). The rate of target vessel failure was 21.6% (27/125) with vascular brachytherapy and 12.4% (32/259) with the sirolimus-eluting stent (relative risk [RR], 1.7; 95% confidence interval [CI], 1.1-2.8; P = .02). Target lesion revascularization was required in 19.2% (24/125) of the vascular brachytherapy group and 8.5% (22/259) of the sirolimus-eluting stent group (RR, 2.3 [95% CI, 1.3-3.9]; P = .004). At follow-up angiography, the rate of binary angiographic restenosis for the analysis segment was 29.5% (31/105) for the vascular brachytherapy group and 19.8% (45/227) for the sirolimus-eluting stent group (RR, 1.5 [95% CI, 1.0-2.2]; P = .07). Compared with the vascular brachytherapy group, minimal lumen diameter was larger in the sirolimus-eluting stent group at 6-month follow-up (mean [SD], 1.52 [0.63] mm vs 1.80 [0.63] mm; P<.001), reflecting greater net lumen gain in the analysis segment (0.68 [0.60] vs 1.0 [0.61] mm; P<.001) due to stenting and no edge restenosis.. Sirolimus-eluting stents result in superior clinical and angiographic outcomes compared with vascular brachytherapy for the treatment of restenosis within a bare-metal stent.. ClinicalTrials.gov Identifier: NCT00231257.

Topics: Aged; Angioplasty, Balloon, Coronary; Bayes Theorem; Brachytherapy; Coronary Angiography; Coronary Restenosis; Female; Humans; Male; Middle Aged; Prospective Studies; Sirolimus; Stents

The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation.. Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation.. Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year.. Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p < 0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p < 0.001), and major adverse cardiovascular events (20% vs. 44%, respectively, p = 0.018).. This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Topics: Administration, Oral; Aged; Angiogenesis Inhibitors; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Female; Follow-Up Studies; Humans; Male; Metals; Middle Aged; Sirolimus; Stents; Treatment Outcome

Saphenous vein graft (SVG) intervention is associated with a significantly increased rate of periprocedural complications and late clinical and angiographic restenosis. In the contemporary drug-eluting stent (DES) era, the comparison of the efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) in SVG interventions is currently unknown. We conducted this retrospective analysis to investigate this issue.. Forty-seven patients with 50 SVG lesions who underwent standard percutaneous coronary intervention (PCI) with SES (SES group) were compared with 42 patients with 45 SVG lesions with PES (PES group). All patients received distal protection devices (DPDs) during the interventions. The in-hospital, 30-day, and 6-month clinical outcomes in both groups were compared. Baseline clinical and procedural characteristics were balanced between both groups except for the proximal and mid lesions. There were no deaths or Q-wave myocardial infarctions (MIs) during the index hospitalization. Non-Q-wave MI was similar between the two groups (SES vs PES, 4.3% vs 7.1%, P=0.55). At 30-day and 6-month follow-ups, all the clinical outcomes were similar between the two groups. There was no subacute thrombosis (SAT) or late thrombosis in either group. The event-free survival at 6 months was also similar between both groups (P=0.75).. The use of DES in patients undergoing SVG intervention with a DPD is clinically safe and feasible. As compared to SES, PES have the same efficacy and clinical outcomes in SVG interventions up to 6 months.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Disease-Free Survival; District of Columbia; Female; Graft Occlusion, Vascular; Hospitalization; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Paclitaxel; Radiography; Saphenous Vein; Severity of Illness Index; Sirolimus; Stents; Treatment Outcome

Sirolimus-eluting stents (SES) have demonstrated low target vessel revascularizations and low incidence of angiographic restenosis in several clinical scenarios. The aim of the present study was to assess the efficacy and safety of SES for the treatment of proximal left anterior descending coronary artery (pLAD) lesions.. Ninety-six patients with severe pLAD stenosis were enrolled. Angiographic and clinical follow-up were performed at 6 and 24 months, respectively. Death, myocardial infarction (MI), new target lesion revascularization (TLR), and target vessel failure (TVF) were registered. Clinical, angiographic, and procedural variables were analyzed to identify predictors of restenosis.. Mean clinical follow-up was 858+/-158 days (26.5+/-8.3 months). Angiographic procedural success was 100%. Angiographic follow-up showed 8.4% of binary restenosis without edge-restenosis phenomenon. Late loss was 0.15+/-0.65 mm; 15.6% of patients had an adverse cardiac event, with 1% of death, 5.2% of MI, 6.3% of TLR, and 9.4% of TVF. At 2 years, the probabilities of cumulative TVF- and TLR-free survival were 90.6% and 93.7%, respectively. Interestingly, no adverse cardiac events were registered between the first and second years. Female gender (OR 10.7 CI 95%[1.7-66.7]) and in-stent restenosis (OR 8.2, CI 95%[1.2-56.4]) were found as independent predictors of binary restenosis. Advanced chronic renal failure showed a strong trend toward worse outcome in terms of binary restenosis (P=0.063).. SES for the treatment of pLAD stenosis proved safe and effective in a long-term follow-up with low incidence of adverse cardiac events and restenosis. Female gender and in-stent restenosis were predictors of binary restenosis.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Radiography; Severity of Illness Index; Sirolimus; Spain; Stents; Treatment Outcome

Although clinical outcomes after sirolimus-eluting stents (SESs) have been previously described ("primary" success rates), the fate of patients whose SES implantation fail and who require ischemia-driven target lesion revascularization is poorly understood. The SIRIUS trial is a prospective, randomized, clinical trial that includes 533 evaluable patients with SESs. Twenty-two of these patients had adjudicated ischemia-driven target lesion revascularization (4.1%) within the first year of follow-up and comprised the study population of this analysis. Of these patients, 11 (50%) had diabetes, and restenotic lesions were focal and located at the proximal stent edge in 91% and 73% of patients, respectively. Restenosis was treated with bare metal stent implantation, balloon dilatation, or intravascular brachytherapy in 82%, 13.5%, and 4.5% of patients, respectively. At 1-year follow-up after the first recurrence (2-year follow-up after the index procedure), only 5 of these patients (23%) required a second repeat revascularization procedure. Risk factors for a second recurrence after treatment of SES restenosis were female gender, long lesions that required long stents at the index procedure, and an early first recurrence. In conclusion, SES failure treated with traditional percutaneous coronary intervention yielded good outcome at 1-year follow-up (secondary failure rate only 23%), perhaps due to the focal nature of the SES restenotic lesion. Future studies should evaluate other methods, including drug-eluting stents, to further optimize the outcome of treatment of SES failures.

Topics: Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Risk Factors; Sirolimus; Stents; Survival Rate; Treatment Failure

We sought to assess the effectiveness of sirolimus-eluting stents (SES) in patients with in-stent restenosis (ISR).. Treatment of patients with ISR remains a challenge.. The Restenosis Intrastent: Balloon Angioplasty Versus Elective Sirolimus-Eluting Stenting (RIBS-II) study is a multicenter randomized trial conducted in 150 patients with ISR (76 allocated to SES and 74 to balloon angioplasty [BA]). The primary end point was recurrent restenosis rate at nine months. Secondary end points included prespecified subgroup analysis, lumen volume on intravascular ultrasound (IVUS), and a composite of major clinical events at one year.. Angiographic success was obtained in all patients. At 9-month angiographic follow-up (96% of eligible patients) minimal lumen diameter was larger (2.52 mm [interquartile range (IQR) 2.09 to 2.81] vs. 1.54 mm [IQR 0.91 to 2.05]; p < 0.001) and recurrent restenosis rate was lower (11% vs. 39%; p < 0.001) in the SES group. Prespecified subgroup analyses were consistent with the main outcome measure. Lumen volume on IVUS at 9 months was also larger (279 mm3 [IQR 227 to 300] vs. 197 mm3 [IQR 177 to 230]; p < 0.001) in the SES group. At one-year clinical follow-up (100% of patients), the event-free survival (freedom from death, myocardial infarction, and target vessel revascularization) was significantly improved in the SES group (88% vs. 69%; p < 0.004) as the result of a lower requirement for target vessel revascularization (11% vs. 30%; p < 0.003).. In patients with ISR, the use of SES provides superior long-term clinical, angiographic, and IVUS outcome than BA treatment.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

This study sought to evaluate the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis (ISR) in consecutive unselected patients undergoing coronary intervention in a real-world scenario.. Restenosis after bare metal stenting is characterized by a high rate of re-restenosis once treated with repeated percutaneous coronary intervention.. The study was designed as a prospective two-center registry. We enrolled 244 patients with ISR in a native coronary artery or saphenous vein graft who had clinical indication for repeat intervention.. Sirolimus stent implantation was successful in all lesions. At 9-month follow-up, death occurred in 4 (1.6%) patients, myocardial infarction in 4 (1.6%), and ischemia-driven target lesion revascularization (TLR) in 12 (4.9%), for a cumulative event-free survival of 227 (93%). Although 9-month follow-up angiography was planned in all patients, only 150 (62%) patients completed it, and restenosis was present in 13 (8.7%) patients. Diabetes and non-ST-segment elevation acute coronary syndrome at presentation were the only independent predictors of freedom from ischemia-driven TLR and major adverse cardiac events.. Sirolimus stent implantation for the treatment of ISR is effective and safe. In diabetic patients and in those with acute coronary syndrome, the higher rate of recurrence requires further evaluation.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Diabetic Angiopathies; Female; Humans; Immunosuppressive Agents; Italy; Male; Middle Aged; Prospective Studies; Registries; Sirolimus; Stents; Survival Analysis; Treatment Outcome

The everolimus-eluting stent (EES) has been shown to significantly decrease neointimal proliferation at 6 months compared with the bare metal stent (BMS) in patients with de novo coronary lesions. We report mid-term outcomes based on different vessel sizes in the combined FUTURE I and II trials. In the prospective, randomized, FUTURE I trial (single center) and expanded FUTURE II trial (multicenter), 106 patients (107 lesions) were randomized to EESs (n = 49 lesions) or BMSs (n = 58 lesions). Patients were categorized into 3 groups based on preprocedure reference diameter as assessed by quantitative coronary angiography (small vessel < 2.75 mm, medium vessel 2.75 to 3.25 mm, and large vessel > 3.25 mm). At 6-month follow-up, EESs decreased in-stent late lumen loss (decreased rate range of 78% to 94%), resulting in significantly larger minimum lumen area as assessed by intravascular ultrasound (increased range of 34% to 42%) compared with the BMS across all vessel sizes. There were no cases of in-stent restenosis with EESs at any vessel size but 8 cases with BMSs (5 in small vessels). No stent thrombosis, aneurysm formation, or late stent incomplete apposition was observed in any group. The EES appears to be effective for treatment of de novo coronary lesions in decreasing neointimal proliferation at 6-month follow-up compared with BMSs, regardless of vessel size.

Topics: Aged; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

Outcomes remain relatively unfavorable for stent-based coronary intervention of lesions with long diseased segments. This study compared sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) for long coronary lesions.. The present randomized, multicenter, prospective study compared the use of long (> or =32 mm) SES with PES in 500 patients with long (> or =25 mm) native coronary lesions. The primary end point of the trial was the rate of binary in-segment restenosis according to follow-up angiography at 6 months. The SES and PES groups had similar baseline characteristics. Lesion length was 33.9+/-11.6 mm in the SES group and 34.5+/-12.6 mm in the PES group (P=0.527). The in-segment binary restenosis rate was significantly lower in the SES group than in the PES group (3.3% versus 14.6%; relative risk 0.23; P<0.001). In-stent late loss of lumen diameter was 0.09+/-0.37 mm in the SES group and 0.45+/-0.55 mm in the PES group (P<0.001). In patients with restenoses, a pattern of focal restenosis was more common in the SES group than in the PES group (100% versus 53.3%, P=0.031). Consequently, SES patients had a lower rate of target-lesion revascularization at 9 months (2.4% versus 7.2%, P=0.012). The incidence of death (0.8% in SES versus 0% in PES, P=0.499) or myocardial infarction (8.8% in SES versus 10.8% in PES, P=0.452) at 9 months of follow-up was not statistically different between the 2 groups.. For patients with long native coronary artery disease, SES implantation was associated with a reduced incidence of angiographic restenosis and a reduced need for target-lesion revascularization compared with PES implantation.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Equipment Design; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Retreatment; Sirolimus; Treatment Outcome

Initial reports on drug-eluting stents (DES) for the treatment for in-stent restenosis (ISR) show very good outcomes. Nevertheless, few data are available on direct comparison with intracoronary brachytherapy (IBT). The aim of this study was to compare brachytherapy and DES in treatment of diffuse ISR.. One hundred forty-one consecutive patients with diffuse ISR were treated with IBT (68 patients; beta (90Sr/90Y) emitters) or with DES (73 patients; 32 with sirolimus-eluting and 41 with paclitaxel-eluting stents). Angiographic and clinical follow-up was scheduled within 9 months.. The first 74 lesions were treated with IBT (group 1) and the latter 74 with DES (group 2). The two groups were well matched for clinical/angiographic characteristics. At follow-up, restenosis rates were 37.8% (28/74) in IBT group and 14.9% (11/74) in DES group (P = .0028). A diffuse pattern of recurrence was more frequent after IBT (20/74 vs 6/74, P = .005). A worse outcome after IBT was associated with the "edge effect," accounting for most failures. Recurrence within the original restenotic stent was similar in both groups (12.9% vs 14.9% in groups 1 and 2 respectively, P = .8).. Drug-eluting stents are more effective than IBT with beta-irradiation in reducing recurrence rates after treatment of diffuse ISR. In case of failure, the pattern of restenosis is more benign after treatment with DES.

Topics: Aged; Beta Particles; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Restenosis; Drug Delivery Systems; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Stents

Sirolimus-eluting stent implantation improves the outcome in simple coronary artery lesions compared with bare metal stents, but there is limited evidence of their safety and efficacy when implanted in complex lesions like coronary bifurcations.. SCANDSTENT was a randomized controlled study comparing implantation of sirolimus-eluting stents with bare-metal stents in patients with complex coronary artery disease. This substudy evaluates the angiographic and clinical outcome of 126 patients with lesions located in a coronary bifurcation.. The baseline characteristics of the patients were comparable: 15% had diabetes, and 1.7 stents were implanted per lesion. At follow-up, the minimum lumen diameter of the main branch was 2.35 mm in patients who received sirolimus-eluting stents compared with 1.68 mm in those who received bare-metal stents, and that of the side branch was 1.70 versus 1.19 mm (both P < .001). The late lumen loss in the main branch was 0.12 mm in the sirolimus-eluting stent group versus 0.99 mm in the bare-metal stent group and 0.03 versus 0.56 mm in the side branch (both P < .001). Thus, sirolimus-eluting stents reduced the restenosis rate from 28.3% to 4.9% in the main branch and from 43.4% to 14.8% in the side branches (both P < .001). Major adverse cardiac events occurred in 9% with sirolimus-eluting stents versus 28% with bare-metal stents (P = .01), and stent thrombosis was observed in 0% versus 9% (P = .02).. Sirolimus-eluting stent implantation improves both the angiographic and clinical outcomes considerably compared with that of bare-metal stents in patients with stenoses located in coronary bifurcations.

Topics: Aged; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Drug Delivery Systems; Equipment Design; Female; Humans; Incidence; Male; Metals; Middle Aged; Sirolimus; Stents; Thrombosis; Treatment Outcome

We sought to compare, in a randomized fashion, sirolimus-eluting stents (SES) versus bare-metal stents (BMS) in saphenous vein grafts (SVGs).. Sirolimus-eluting stents reduce restenosis and repeated revascularization in native coronary arteries compared with BMS. However, randomized data in SVG are absent.. Patients with SVG lesions were randomized to SES or BMS. All were scheduled to undergo 6-month coronary angiography. The primary end point was 6-month angiographic in-stent late lumen loss. Secondary end points included binary angiographic restenosis, neointimal volume by intravascular ultrasound and major adverse clinical events (death, myocardial infarction, target lesion, and vessel revascularization).. A total of 75 patients with 96 lesions localized in 80 diseased SVGs were included: 38 patients received 60 SES for 47 lesions, whereas 37 patients received 54 BMS for 49 lesions. In-stent late loss was significantly reduced in SES (0.38 +/- 0.51 mm vs. 0.79 +/- 0.66 mm in BMS, p = 0.001). Binary in-stent and in-segment restenosis were reduced, 11.3% versus 30.6% (relative risk [RR] 0.37; 95% confidence interval [CI] 0.15 to 0.97, p = 0.024) and 13.6% versus 32.6% (RR 0.42; 95% CI 0.18 to 0.97, p = 0.031), respectively. Median neointimal volume was 1 mm(3) (interquartile range 0 to 13) in SES versus 24 (interquartile range 8 to 34) in BMS (p < 0.001). Target lesion and vessel revascularization rates were significantly reduced, 5.3% versus 21.6% (RR 0.24; 95% CI 0.05 to 1.0, p = 0.047) and 5.3% versus 27% (RR 0.19; 95% CI 0.05 to 0.83, p = 0.012), respectively. Death and myocardial infarction rates were not different.. Sirolimus-eluting stents significantly reduce late loss in SVG as opposed to BMS. This is associated with a reduction in restenosis rate and repeated target lesion and vessel revascularization procedures. (The RRISC Study; http://clinicaltrials.gov/ct/show; NCT00263263).

Topics: Aged; Aged, 80 and over; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Saphenous Vein; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

Direct stenting without balloon predilatation has been shown to be feasible and safe with drug-eluting stents, but no randomized comparisons between the two strategies exist. This study was designed to compare direct stenting with balloon predilatation followed by stent placement using only drug-eluting stents.. One hundred and sixty-six consecutive coronary lesions in 95 consenting patients (mean age 59 +/- 11 years; 12 women) were randomly assigned to direct stenting (n = 88), or balloon predilatation followed by stenting (n = 78), using sirolimus- or paclitaxel-eluting stents.. All procedures were uneventful. Crossover to balloon predilatation was necessary in 6 (7%) lesions randomized to direct stenting. During a 12-month follow up period, ischemia-driven angiography was performed in 13 patients. By intention to treat analysis, target lesion revascularization was required in 4 lesions, all of which were randomized to the predilatation group (p = 0.04).. Direct stenting was feasible in up to 93% of attempted lesions. A strategy of direct stenting resulted in a significantly lower rate of target lesion revascularization over a 12-month follow-up period compared to balloon predilatation followed by stenting.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Male; Middle Aged; Probability; Prospective Studies; Risk Assessment; Sirolimus; Statistics, Nonparametric; Stents; Survival Rate; Treatment Outcome; Vascular Patency

To compare the effect of sirolimus-eluting stents to paclitaxel-eluting stents in complex and diffuse coronary lesions.. 138 consecutive patients with complex and diffuse coronary lesions were enrolled from April 2004 to August 2005; they were implanted with more than 25 mm long sirolimus-eluting stents or paclitaxel-eluting stents. Unsuccessful cases were excluded. All patients received medical treatment according to guideline. Aspirin 300 mg and clopidogrel 75 mg once daily were continually administered for 6 months after the procedure. The patients were followed up after 6 months.. The study population consisted of 138 patients, including 124 men and 14 women. There were 129 (87.8%) C ACC/AHA type lesions. The average reference vessel diameter was (2.91 +/- 0.43) mm. The average lesion length was (36.36 +/- 12.27) mm. The average stent length per lesion was (40.25 +/- 12.79) mm. There was no difference of patient and lesion baseline characteristics between the groups of sirolimus-eluting and paclitaxel-eluting stents. At the end of follow up, in-stent restenosis rate (5.9% vs 17.7%, P = 0.023) and in-segment restenosis rate (9.4% vs 21.0%, P = 0.048) in the group of sirolimus-eluting stents were less than that in the group of paclitaxel-eluting stents. The difference was also seen in in-stent late luminal loss [(0.26 +/- 0.46) mm vs (0.60 +/- 0.66) mm, P = 0.001)] and in-segment late lumens loss [(0.16 +/- 0.52) mm vs (0.45 +/- 0.65) mm, P = 0.003)]. There was no difference between the sirolimus-eluting stents group and paclitaxel-eluting stents group in the incidence of target lesion revascularization (7.1% vs 12.9%, P = 0.223).. In patients with complex and diffuse coronary lesions, the use of the sirolimus-eluting stent was associated with a decrease in the extent of late luminal loss, as compared with use of paclitaxel-eluting stents, suggesting that sirolimus-eluting stent might be more suitable to be used in small vessel.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paclitaxel; Sirolimus; Stents; Treatment Outcome

In patients with de novo coronary lesions, drug-eluting stents have drastically reduced restenosis risk compared with bare metal stents and conventional balloon angioplasty. It is less clear whether drug-eluting stents are superior to conventional balloon angioplasty for the treatment of patients with in-stent restenosis.. To assess if drug-eluting stents are a more effective treatment of in-stent restenosis than conventional balloon angioplasty, and to assess the relative merits of 2 drug-eluting stents, a sirolimus-eluting stent and a paclitaxel-eluting stent.. Randomized, open-label, active-controlled trial conducted among 300 patients with angiographically significant in-stent restenosis in 2 tertiary German centers from June 1, 2003, to October 20, 2003.. After pretreatment with 600 mg of clopidogrel for at least 2 hours before intervention, all patients were randomly assigned to 1 of 3 treatment groups: sirolimus stent, paclitaxel stent, or balloon angioplasty (100 patients in each group).. Primary end point: angiographic restenosis (diameter stenosis > or =50%) at 6-month follow-up angiography based on "in-segment" analysis. Primary analysis was comparison between stent groups and balloon angioplasty groups; a secondary analysis compared sirolimus and paclitaxel stents.. Follow-up angiography was performed in 275 (92%) of 300 patients. The incidence of angiographic restenosis was 44.6% (41/92) in the balloon angioplasty group, 14.3% (13/91) in the sirolimus stent group (P<.001 vs balloon angioplasty), and 21.7% (20/92) in the paclitaxel stent group (P = .001 vs balloon angioplasty). When compared with balloon angioplasty, receiving a sirolimus stent had a relative risk (RR) of angiographic restenosis of 0.32 (95% confidence interval [CI], 0.18-0.56); a paclitaxel stent had an RR of 0.49 (95% CI, 0.31-0.76). The incidence of target vessel revascularization was 33.0% (33/100) in the balloon angioplasty group, 8.0% (8/100) in the sirolimus stent group (P<.001 vs balloon angioplasty), and 19.0% (19/100) in the paclitaxel stent group (P = .02 vs balloon angioplasty). The secondary analysis showed a trend toward a lower rate of angiographic restenosis (P = .19) and a significantly lower rate of target vessel revascularization (P = .02) among sirolimus stent patients compared with paclitaxel stent patients.. In patients with in-stent restenosis, a strategy based on sirolimus- or paclitaxel-eluting stents is superior to conventional balloon angioplasty for the prevention of recurrent restenosis. Sirolimus-eluting stents may be superior to paclitaxel-eluting stents for treatment of this disorder.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Female; Humans; Male; Middle Aged; Paclitaxel; Platelet Aggregation Inhibitors; Risk; Secondary Prevention; Sirolimus; Stents

The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term.. This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months.. Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation.

Topics: Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Revascularization; Sirolimus; Stents; Time

Drug-eluting stents have considerably reduced restenosis. Their relative merits have been assessed on the basis of comparisons made with control bare stents with thick struts. However, increased strut thickness negatively affects restenosis. No direct comparisons between drug-eluting stents and bare stents with thin struts have been performed. The aim of this study was to evaluate the relative efficacy of sirolimus-eluting stents (Cypher) as compared with that of bare stents with thin struts (BeStent 2).. A total of 500 patients with coronary artery disease were randomly assigned to receive a Cypher stent or BeStent. The primary endpoint was angiographic restenosis defined as a stenosis diameter > or = 50% at 6-month angiographic follow-up. The secondary endpoint was the need for target vessel revascularization (TVR) during the year following the procedure. Follow-up angiography was performed in 81.8% of the patients. Patients treated with Cypher stents had a lower angiographic restenosis rate [8.3 vs. 25.5%, relative risk, 0.33 (95% confidence interval, 0.19-0.56), P<0.001] and a lower incidence of TVR [7.2 vs. 18.8%, relative risk, 0.38 (0.22-0.66), P<0.001]. For smaller vessels (< 2.8 mm), the angiographic restenosis rates were 7.0% with the Cypher stent and 34.2% with the BeStent (P<0.001). For larger vessels (> or = 2.8 mm), angiographic restenosis rates were 10.0% with the Cypher stent and 13.1% with the BeStent (P=0.52).. The drug-eluting stent, Cypher, is associated with a significantly lower risk of restenosis compared with the bare thin-strut BeStent. The advantage of the Cypher stent is vastly reduced in large vessels.

Topics: Aged; Coronary Restenosis; Drug Implants; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Prospective Studies; Sirolimus; Stents; Treatment Outcome

Rapamycin- and taxol-eluting stents have been shown to reduce restenosis, but there are no large-scale studies of their usefulness in lesions with a high risk of restenosis, or of the relative merits of the two devices. This prospective study compared their safety and efficacy in lesions with a high risk of restenosis.. We included consecutive patients with lesions to treat that met at least one of the following criteria: a) in-stent restenosis; b) diffuse (>20 mm) restenosis; c) small vessel (< or =2.5 mm) restenosis; or d) total occlusion. Patients received different devices along three consecutive study periods: bare metal (conventional) stents, sirolimus-eluting (rapamycin) stents and paclitaxel-eluting (taxol) stents.. One hundred patients in each group were included, for a total of 300 patients. In the sirolimus group, after 8.5+/-2 months of follow-up, there were 2 late thromboses (2%) and only 1 patient (1%) required target lesion revascularization. In the paclitaxel group 2 patients (2%) had in-hospital stent thrombosis (1 acute, 1 subacute), and after 9+/-2.5 months of follow-up only 1 patient (1%) needed target lesion revascularization. In the conventional group, after 8+/-2 months of follow-up, there was 1 subacute thrombosis (1%) and 15 patients (15%) had clinical restenosis requiring target lesion revascularization. Event-free survival curves were significantly better with drug-eluting stents (P<.01 vs conventional stents).. Rapamycin- and taxol-eluting stents were safe for lesions with a high risk of restenosis. These stents were associated with a lower rate of target lesion revascularization during follow-up compared to bare metal stents.

Topics: Coronary Restenosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paclitaxel; Polymers; Prospective Studies; Risk Factors; Sirolimus; Stents

To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study.. Multicentre, double blind, randomised trial.. Percutaneous coronary intervention for single de novo coronary lesions.. 238 patients with stable or unstable angina.. Randomisation to sirolimus eluting stent or bare stent implantation.. Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs.. At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the additional one year costs at 166.. The one year data from RAVEL suggest an attractive balance between costs and effects for sirolimus eluting stents in the treatment of single native de novo coronary lesions. The cost effectiveness of drug eluting stents in more complex lesion subsets remains to be determined.

Topics: Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Cost-Benefit Analysis; Disease-Free Survival; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Metals; Netherlands; Sirolimus; Stents; Surface Properties

Sirolimus systemic administration has shown marked inhibition of neointimal hyperplasia (NIH) after balloon angioplasty in porcine models. In this pilot study, we tested the hypothesis that oral sirolimus is safe and effective to inhibit in-stent NIH and therefore to prevent and treat in-stent restenosis (ISR). Twelve patients (18 lesions) with high risk for ISR, including 8 ISR lesions, were admitted. One day before the procedure, patients were given a 15 mg loading dose of oral sirolimus, followed by 5 mg daily for 28 days, with weekly whole blood level measurements. The daily dose was adjusted to keep the concentration at 10-15 ng/ml. Sirolimus was well tolerated by all patients but one, who died at the end of the third week of treatment. The 4- and 8-month follow-up revealed an angiographic late loss of 0.40 +/- 0.24 and 0.67 +/- 0.45 mm (P < 0.01), respectively. At the same time points, the intravascular ultrasound in in-stent relative volumetric obstruction was 14.4% +/- 9.1% and 23.2% +/- 10.1% (P < 0.01), respectively. At 24-month clinical follow-up, adverse events were one (8.3%) death, two (11.1%) target lesion, and four (22.2%) target vessel revascularizations. In conclusion, in this small group of high-risk ISR patients, oral sirolimus inhibited NIH and therefore may be an effective strategy for the prevention and treatment of ISR.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Probability; Risk Assessment; Severity of Illness Index; Sirolimus; Statistics, Nonparametric; Stents; Treatment Outcome; Ultrasonography, Interventional; Vascular Patency

In-stent restenosis is notoriously difficult to treat by repeat catheter intervention because of its propensity for aggressive recurrent neointimal formation. This study sought to assess the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis.. The study was designed as a prospective multicenter registry. We included 162 patients with in-stent restenosis of a native coronary artery who had a clinical indication for repeat intervention. Patients were scheduled for follow-up angiography at 6 months. The primary end point was in-lesion late loss. Follow-up angiography was performed in 155 patients. We obtained an in-lesion late loss of 0.08+/-0.49 mm and a binary restenosis rate of 9.7% (15/155), which prompted reintervention in 7.4% (12/162) at 9 months. The 9-month rate of death was 1.2% (2/162) and that of nonfatal myocardial infarction was 1.2% (2/162).. Sirolimus-eluting stents were highly efficacious and safe in the treatment of in-stent restenosis. Our study provides rationale for the use of sirolimus-eluting stents in the treatment of in-stent restenosis.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Myocardial Infarction; Sirolimus; Stents; Survival Rate; Treatment Outcome

We prospectively studied the inflammatory response to coronary stenting (calculated as the difference between the highest postprocedural C-reactive protein [CRP] and baseline CRP levels [DeltaCRP]) and restenosis in 301 patients who received a sirolimus-eluting stent (n = 149) or a bare stent (n = 152) in the setting of a randomized trial. Median values of DeltaCRP were 3.1 mg/L in the sirolimus-eluting stent group and 3.0 mg/L in the bare stent group (p = 0.71). In the sirolimus-eluting group, restenotic rates were 9.7% in the subgroup with DeltaCRP higher than the median and 11.5% in the subgroup with DeltaCRP no higher than the median (p = 0.37). In the bare stent group, restenotic rates were 28.6% in the subgroup with DeltaCRP higher than the median and 15.4% in the subgroup with DeltaCRP no higher than the median (p = 0.04).

Topics: Aged; Angioplasty, Balloon, Coronary; C-Reactive Protein; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Humans; Immunosuppressive Agents; Male; Prospective Studies; Sirolimus; Stents; Treatment Outcome

We sought to determine the safety and efficacy of using multiple overlapping drug-eluting stents (DES) in patients with diffuse left anterior descending coronary artery (LAD) disease.. Diffuse LAD disease represents a therapeutic challenge. Results after coronary artery bypass surgery are suboptimal, whereas the use of bare metal stents is limited by high rates of restenosis. The introduction of DES prompted treatment of long diffuse disease with multiple overlapping stents.. All consecutive patients with de novo diffuse LAD disease treated with more than 60-mm long DES from April 2002 to March 2004 were analyzed.. The study population consisted of 66 patients. Thirty-nine patients were treated with sirolimus-eluting stents (SES), average length 84 +/- 22 mm, and 27 patients with paclitaxel-eluting stents (PES), average length 74 +/- 14 mm. The number of stents implanted per patient was 2.8 +/- 0.7, whereas the mean total stent length for the LAD treatment was 80 +/- 20 mm. Angiographic as well as procedural success was achieved in 95% of cases. Eleven (16.6%) patients had in-hospital non-Q-wave myocardial infarction (five SES and six PES), and one patient developed intraprocedural stent thrombosis. All patients had clinical follow-up, and 52 patients (79%) had an angiographic follow-up at six months. Hierarchical major adverse cardiac event rate was 15% (7.5% for SES and 7.5% for PES). No patients died, one patient had non-Q-wave myocardial infarction (non-index vessel), and 10 patients (15%) underwent target vessel revascularization.. The implantation of multiple overlapping DES in patients with a diffusely diseased LAD is relatively safe and associated with good midterm clinical outcomes.

Topics: Administration, Topical; Aged; Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Sirolimus; Stents; Treatment Outcome

We analyzed the clinical, angiographic, and late intravascular ultrasonographic findings from 140 patients whose in-stent restenosis was treated with sirolimus-eluting stents. In-stent restenosis remains the main limitation to percutaneous coronary revascularization and has a high recurrence rate after bare stent implantation. From May 2002 through July 2003, we studied 140 patients with clinical restenosis after bare-stent treatment. In 107 patients, in-stent restenosis occurred de novo; in 28 patients, this was the 2nd restenosis; and in another 5, it was the 3rd occurrence. A sirolimus-eluting stent was implanted directly after angiographic evaluation of the in-stent restenosis in 79 patients and after pre-dilation in 61 patients. All patients were given the following antithrombotic regimen: low-molecular-weight heparin, ticlopidine, and aspirin for 1 month, followed by clopidogrel and aspirin for 1 year. Primary success was achieved in 137 patients. Three patients had a non-Q wave myocardial infarction. At the 1-month evaluation, 2 patients had died: 1 due to subacute stent thrombosis and another due to acute mesenteric ischemia. After a mean follow-up of 16 +/- 4 months, the major adverse cardiac events were acute myocardial infarction due to late stent thrombosis in 2 patients and the need for target lesion revascularization in 15 patients. Late angiographic evaluation was performed in 97 patients (69%), 16 of whom had new restenosis: 14 of the restenoses were intrastent, and 2 were at the edges of the stent. Our results suggest that sirolimus-eluting stents are effective in the prevention of in-stent restenosis and, therefore, may become the leading treatment alternative for patients with in-stent restenosis.

Topics: Aged; Coronary Restenosis; Drug Delivery Systems; Female; Humans; Immunosuppressive Agents; Male; Prospective Studies; Sirolimus; Stents; Time Factors

With the use of coronary stents for the treatment of coronary artery disease, in-stent restenosis became a major clinical problem. In this non-randomized study, we examined the use of stent-based delivery of sirolimus (rapamycin) for the treatment of in-stent restenosis in comparison to intracoronary beta-brachytherapy, regarding the clinical effectiveness and the angiographic results for the treatment of in-stent restenosis after 6-9 months.. Between July 2001 and May 2002, 28 patients (65+/-11 years) with instent restenosis were treated with intracoronary brachytherapy. Consecutively, between May 2002 and April 2003, 28 patients (65+/-10 years) with in-stent restenosis were treated with the implantation of a sirolimus-eluting stent (SES). Patients with in-stent restenosis treated by implantation of a SES had significantly lower incidence of in-stent restenosis (1/28 (3.6%) vs 10/28 (36%); p=0.007) and insegment restenosis (4/28 (14%) vs 14/28 (50%); p=0.013) compared to patients treated with brachytherapy. Target lesion and target vessel revascularization rate tended to be lower in the SES group (14 vs 25%) but did not yet reach statistical significance. One patient died in the group treated by implantation of a SES eight months after stenting, one patient suffered from myocardial infarction due to a subtotal in-stent restenosis after brachytherapy. Two patients after brachytherapy underwent surgical revascularization due to recurrent in-stent restenosis similar to the patient with in-stent restenosis after SES implantation.. In this study we show the feasibility and safety of the treatment of in-stent restenosis by implantation of sirolimus-eluting stents and demonstrate a lower incidence of recurrent in-stent restenosis as well as lower late luminal loss compared to treatment by intravascular brachytherapy.

Topics: Age Distribution; Aged; Blood Vessel Prosthesis; Brachytherapy; Coronary Restenosis; Disease-Free Survival; Female; Germany; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Radiography; Risk Assessment; Risk Factors; Sex Distribution; Sirolimus; Stents; Treatment Outcome

Drug-eluting stents (DES) represent a major advance in interventional cardiology. Along with the success shown, current DES also present limitations related to the presence of polymer-coating, fixed drug, and dose used. With the ISAR (Individualized Drug-Eluting Stent System to Abrogate Restenosis) project, a DES system has been developed that permits individualized choice of the drug and dose to use for the given patient. The objective of this prospective dose finding study was to assess the feasibility, safety, and efficacy of a polymer-free on-site stent coating with increasing rapamycin doses.. In this dose finding study, 602 patients were sequentially enrolled in four groups: microporous bare metal stent (BMS), DES stents coated with a 0.5, 1.0, and 2.0% rapamycin solution. The angiographic in-segment restenosis rate at follow-up angiography was the primary study endpoint. In-segment restenosis was significantly reduced from 25.9% with BMS to 18.9, 17.2, and 14.7% with 0.5, 1.0, and 2.0% rapamycin-eluting stents, respectively (P=0.024). Similarly, the need for target lesion revascularization at 1 year follow-up was reduced from 21.5% with BMS to 16.4, 12.6, and 8.8% with 0.5, 1.0, and 2.0% rapamycin-eluting stents, respectively (P=0.006).. The placement of polymer-free stents coated on-site with rapamycin is feasible and safe. Furthermore, a dose-dependent efficacy in restenosis prevention is achievable with this new DES concept.

Topics: Aged; Coronary Restenosis; Dose-Response Relationship, Drug; Drug Implants; Feasibility Studies; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Polymers; Prospective Studies; Regression Analysis; Sirolimus; Stents; Treatment Outcome

Diabetes mellitus is a well-known risk factor for future adverse cardiac events after coronary intervention with conventional metal stents. In this study, the impact of sirolimus-eluting stents (SES) were evaluated in a consecutive group of diabetic patients undergoing elective percutaneous coronary treatment and compared to a population treated with bare metal stents.. From April 2002, a policy of routine SES implantation has been instituted in our hospital. During 1 year of enrollment, a total of 112 consecutive diabetic patients with de novo coronary lesions were electively treated with SES (SES group). A similar group for comparison comprised 118 consecutive patients treated with bare metal stents in the preceding period (the pre-SES group). After 1-year follow-up, the cumulative rate of major adverse cardiac events (death, myocardial infarction, and any repeat revascularization) was 17.3% in the SES group versus 30.2% in the pre-SES group (hazard ratio, 0.54 [95% confidence interval, 0.32-0.91]; p = 0.02), mainly due to a marked reduction in the need for repeat revascularization (10.2% versus 23.5%; hazard ratio, 0.40 [95% confidence interval, 0.21-0.78]; p = 0.007).. Routine utilization of SES for diabetic patients significantly reduces the rate of adverse cardiac events at 1 year compared to bare metal stents.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Coronary Artery Disease; Coronary Restenosis; Diabetes Complications; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Reoperation; Risk Factors; Sirolimus; Stents; Treatment Outcome

The aim of the study was to compare the angioplasty mechanisms of drug (sirolimus)-eluting stent (DES) implantation and vascular brachytherapy (VBT) for the treatment of in-stent restenosis (ISR) as assessed by intravascular ultrasound (IVUS).. We performed IVUS in 53 patients (28 DES, 25 VBT) before and after angioplasty of ISR and at 6-month follow-up. Cross-sectional areas of the external elastic membrane, the stent, and the lumen were measured. Plaque + media, peristent plaque, and intimal hyperplasia areas were calculated, respectively.. Clinical and IVUS baseline characteristics did not differ between groups at baseline. After the index procedure, the lumen at the stent site was smaller in the DES group (DES 6.7 +/- 2.0 mm2 vs VBT 7.5 +/- 2.2 mm2, P = .042). Because of less intimal hyperplasia (DES 0.2 +/- 0.5 mm2 vs VBT 0.7 +/- 0.7 mm2, P = .043), the lumen dimensions revealed no difference between groups at follow-up (DES 6.5 +/- 2.3 mm2 vs VBT 6.8 +/- 2.2 mm2, P = .374). At the reference site, the index procedure led to a similar increase of plaque + media (DES 0.9 +/- 0.9 mm2 vs VBT 0.6 +/- 1.2 mm2, P = .150). At follow-up, the plaque + media was significantly smaller in the DES group (DES 8.0 +/- 6.6 mm2 vs VBT 9.9 +/- 7.8 mm2, P = .013).. Drug-eluting stent for the treatment of ISR more effectively inhibits neointima formation when compared with VBT. Yet insufficient stent expansion might be a reason for device failure and should be avoided. At the reference site, lumen loss by an increased plaque burden, as has been well recognized following VBT, is not present with DES.

Topics: Aged; Angioplasty, Balloon; Beta Particles; Brachytherapy; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug Implants; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Sirolimus; Stents; Time Factors; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Sirolimus-eluting stents and paclitaxel-eluting stents, as compared with bare-metal stents, reduce the risk of restenosis. It is unclear whether there are differences in safety and efficacy between the two types of drug-eluting stents.. We conducted a randomized, controlled, single-blind trial comparing sirolimus-eluting stents with paclitaxel-eluting stents in 1012 patients undergoing percutaneous coronary intervention. The primary end point was a composite of major adverse cardiac events (death from cardiac causes, myocardial infarction, and ischemia-driven revascularization of the target lesion) by nine months. Follow-up angiography was completed in 540 of 1012 patients (53.4 percent).. The two groups had similar baseline clinical and angiographic characteristics. The rate of major adverse cardiac events at nine months was 6.2 percent in the sirolimus-stent group and 10.8 percent in the paclitaxel-stent group (hazard ratio, 0.56; 95 percent confidence interval, 0.36 to 0.86; P=0.009). The difference was driven by a lower rate of target-lesion revascularization in the sirolimus-stent group than in the paclitaxel-stent group (4.8 percent vs. 8.3 percent; hazard ratio, 0.56; 95 percent confidence interval, 0.34 to 0.93; P=0.03). Rates of death from cardiac causes were 0.6 percent in the sirolimus-stent group and 1.6 percent in the paclitaxel-stent group (P=0.15); the rates of myocardial infarction were 2.8 percent and 3.5 percent, respectively (P=0.49); and the rates of angiographic restenosis were 6.6 percent and 11.7 percent, respectively (P=0.02).. As compared with paclitaxel-eluting stents, the use of sirolimus-eluting stents results in fewer major adverse cardiac events, primarily by decreasing the rates of clinical and angiographic restenosis.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Proportional Hazards Models; Single-Blind Method; Sirolimus; Stents; Survival Analysis

Drug-eluting stents are highly effective in reducing the rate of in-stent restenosis. It is not known whether there are differences in the effectiveness of currently approved drug-eluting stents in the high-risk subgroup of patients with diabetes mellitus.. We enrolled 250 patients with diabetes and coronary artery disease: 125 were randomly assigned to receive paclitaxel-eluting stents, and 125 to receive sirolimus-eluting stents. The primary end point was in-segment late luminal loss. Secondary end points were angiographic restenosis (defined as in-segment stenosis of at least 50 percent at follow-up angiography) and the need for revascularization of the target lesion during a nine-month follow-up period. The study was designed to show noninferiority of the paclitaxel stent as compared with the sirolimus stent, defined as a difference in the extent of in-segment late luminal loss of no more than 0.16 mm.. The extent of in-segment late luminal loss was 0.24 mm (95 percent confidence interval, 0.09 to 0.39) greater in the paclitaxel-stent group than in the sirolimus-stent group (P=0.002). In-segment restenosis was identified on follow-up angiography in 16.5 percent of the patients in the paclitaxel-stent group and 6.9 percent of the patients in the sirolimus-stent group (P=0.03). Target-lesion revascularization was performed in 12.0 percent of the patients in the paclitaxel-stent group and 6.4 percent of the patients in the sirolimus-stent group (P=0.13).. In patients with diabetes mellitus and coronary artery disease, use of the sirolimus-eluting stent is associated with a decrease in the extent of late luminal loss, as compared with use of the paclitaxel-eluting stent, suggesting a reduced risk of restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetes Complications; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Regression Analysis; Sirolimus; Stents; Survival Analysis

This study was designed to evaluate the clinical and angiographic outcomes of sirolimus-eluting stent (SES) implantation for ostial left anterior descending (LAD) lesions compared with bare-metal stent (BMS) implantation.. The effectiveness of SES implantation for ostial LAD lesions is currently unknown.. Sirolimus-eluting stents were implanted in 68 consecutive patients with ostial LAD stenoses. The control group was composed of 77 patients treated with BMS during the preceding two years. In the SES group, for complete lesion coverage, stent positioning was intentionally extended into the distal left main coronary artery (LMCA) in 23 patients (34%) with intermediate LMCA narrowing.. Compared with the BMS group, the SES group had more multivessel involvement, received fewer debulking atherectomies, underwent more direct stenting, had a greater number of stents, and had more segments stented. The procedural success rate was 100% in both groups. The six-month angiographic restenosis rate was significantly lower in the SES group than in the BMS group (5.1% vs. 32.3%, p < 0.001). During the one-year follow-up period, neither death nor myocardial infarction occurred in either group, but target lesion revascularization was less frequent in the SES group than in the BMS group (0% vs. 17%, p < 0.001). In the SES group, there were no restenoses in cases with LMCA coverage, compared with three restenoses (7.9%) in cases with precise stent positioning (p = NS).. Sirolimus-eluting stent implantation in ostial LAD lesions achieved excellent results regarding restenosis and clinical outcomes compared with BMS implantation. This finding may be associated with reduced neointimal hyperplasia and complete lesion coverage.

Topics: Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Delayed-Action Preparations; Drug Delivery Systems; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Sirolimus; Stents; Ultrasonography

A pharmacokinetic (PK) study was conducted to evaluate sirolimus-eluting stents (SES) in Japanese people, representing the first clinical trial of the use of drug-eluting stents in Japan.. The PK study was conducted in 20 patients with 30 lesions treated with sirolimus-coated BX Velocity stents. All lesions were treated with a single SES (3 x 18 mm). Angiographic follow-up was performed at 8 months after SES implantation, and the clinical outcomes were evaluated at 1 year in all cases. All procedures were successful, and all patients were discharged without any adverse cardiac events. The total restenosis rate was 10% (3 lesions) and target vessel revascularization was performed in those 3 cases (15%). Restenoses occurred at the proximal and distal stent margins. Intravascular ultrasound examination of restenosis cases revealed abundant plaque burden at the stent edges even though the luminal area was preserved.. The sirolimus-eluting BX Velocity stent is safe and useful for Japanese patients with coronary artery disease. However, restenosis at proximal stent edge seems to be a problem.

Topics: Aged; Coronary Angiography; Coronary Disease; Coronary Restenosis; Humans; Immunosuppressive Agents; Japan; Middle Aged; Sirolimus; Stents

Outcomes after percutaneous coronary interventions in diabetic patients are shadowed by the increased rate of recurrence compared with nondiabetic patients.. We conducted a multicenter, randomized trial to demonstrate the efficacy of sirolimus-eluting stents compared with standard stents to prevent restenosis in diabetic patients with de novo lesions in native coronary arteries. The primary end point of the trial was in-segment late lumen loss as assessed by quantitative coronary angiography at 9-month follow-up. The trial was stratified by diabetes treatment status. One hundred sixty patients were randomized to sirolimus-eluting stents (80 patients; 111 lesions) or standard stent implantation (80 patients; 110 lesions). On average, reference diameter was 2.34+/-0.6 mm, lesion length was 15.0+/-8 mm, and 13.1% of lesions were chronic total occlusions. In-segment late lumen loss was reduced from 0.47+/-0.5 mm for standard stents to 0.06+/-0.4 mm for sirolimus stents (P<0.001). Target-lesion revascularization and major adverse cardiac event rates were significantly lower in the sirolimus group (31.3% versus 7.3% and 36.3% versus 11.3%, respectively; both P<0.001). Non-insulin- and insulin-requiring patients demonstrated similar reductions in angiographic and clinical parameters of restenosis after sirolimus-eluting stent implantation. During the 9-month follow-up, stent thrombosis occurred in 2 patients after standard stent implantation. Conversely, this phenomenon was not seen in the sirolimus stent group.. This randomized trial demonstrated that sirolimus stent implantation is safe and efficacious in reducing both angiographic and clinical parameters of restenosis compared with standard stents in diabetic patients with de novo coronary stenoses.

Topics: Aged; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Coronary Restenosis; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Equipment Design; Female; Humans; Male; Middle Aged; Sirolimus; Stents

The effect of lesion characteristics on neointimal hyperplasia after sirolimus-eluting stent implantation was examined in 45 patients who underwent successful preinterventional intravascular ultrasound. There were no differences in neointimal hyperplasia between the moderate/severe calcified lesion group (calcium arc >120 degrees ) and the non/mild calcified lesion group or between the positive vessel remodeling group (external elastic membrane area at the minimal lumen area site larger than that at the proximal reference site) and negative vessel remodeling group. No correlation between preinterventional plaque burden and neointimal hyperplasia was found. In patients who have coronary artery disease, sirolimus-eluting stents continue to demonstrate striking suppression of neointimal proliferation, irrespective of lesion characteristics previously associated with greater restenotic risk.

Topics: Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications; Prospective Studies; Prosthesis Failure; Risk Factors; Severity of Illness Index; Sirolimus; Stents; Tunica Intima; Ultrasonography, Interventional

Treatment of in-stent restenosis (ISR) remains a therapeutic challenge since many pharmacological and mechanical approaches have shown disappointing results except for brachytherapy. Drug-eluting stents (DES) have been reported to effectively reduce ISR in de novo lesions. We studied 55 consecutive patients with ISR in native coronary arteries and 7 with ISR in saphenous vein grafts (SVG) with elective indication for percutaneous coronary intervention (PCI), who underwent successful implantation with DES. No in-hospital postprocedural major adverse cardiac events were observed. All but one patient (n=61) underwent an angiographic follow-up at 183+/-30 days. Grade of stenosis was assessed by quantitative coronary angiography (QCA) at index procedure and at control angiography. Restenosis (>50%) occurred in 5 patients (8.2%). Target vessel revascularization was performed in an additional 4 patients. Minimal intimal hyperplasia was observed in all segments covered by DES (late loss 0.08+/-0.37 mm, loss index 0.11+/-0.47). One patient suffered from subacute stent thrombosis due to discontinuation of clopidogrel medication. At six month follow-up two patients had died. Death was not related to a restenosis in the treated segment. Conclusion Our experiences with DES treatment of ISR lesions show good angiographic and clinical results at index procedure and at the 6 month follow-up with low sub acute thrombosis rate as compared with existing treatment modalities. Restenosis rate seems to be at least as low as reported for brachytherapy.

Topics: Blood Vessel Prosthesis; Coronary Restenosis; Drug Implants; Equipment Design; Equipment Failure Analysis; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Radiography; Sirolimus; Stents; Treatment Outcome

Topics: Administration, Oral; Aged; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Double-Blind Method; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Prosthesis Failure; Retrospective Studies; Sirolimus; Stents; Treatment Outcome

The effectiveness of SES to reduce the risk of restenosis was initially demonstrated in short lesions using stent implantation with routine pre-dilatation and post-dilatation. This intravascular ultrasound (IVUS) substudy of the E-SIRIUS trial sought to evaluate local arterial responses to sirolimus-eluting stents (SES) delivered with a stent implantation technique allowing direct stenting and only selectively applying high-pressure post-dilatation.. IVUS was performed immediately after intervention and at 8-month follow-up in 51 patients randomised to either bare-metal stents (BMS; Bx-Velocitytrade mark; N=20) or SES (Cyphertrade mark N=31). Direct stenting was allowed (24%) and post-dilation was performed only selectively (32%). Lumen dimensions, intimal hyperplasia and vessel remodeling were compared between SES and BMS. Subsequently, results of SES in the E-SIRIUS IVUS substudy (N=31) were compared to those of SES in the IVUS substudy of the SIRIUS trial (N=137). SES in SIRIUS IVUS substudy were delivered with 100% pre-dilatation and 77% post-dilatation. Baseline stent and reference segment measurements were similar between BMS and SES in E-SIRIUS IVUS patients. Using SES there was a 96% reduction in intimal hyperplasia volume within the stented segment (1.8+/-4.9 vs 50.6+/-39.7 mm3, P<0.001) and a significantly larger minimal lumen cross sectional area at 8-month follow-up (4.5+/-1.1 vs 2.3+/-0.9 mm2, P<0.001). No vessel remodeling was observed with the use of SES. The applied stent implantation technique resulted in a minimal stent/reference vessel area ratio of 0.75+/-0.17 in E-SIRIUS SES as compared to 0.84+/-0.23 in SIRIUS SES (P=0.046). Mean intimal hyperplasia cross-sectional area at follow-up was 0.1+/-0.2 mm2 in the SES group of E-SIRIUS and 0.5+/-0.8 mm2 in the SES group of SIRIUS (P=0.003).. An implantation technique of SES which includes direct stenting and minimizes the use of high-pressure post-dilatation results in less optimal stent expansion. However, follow-up results compare very favourable to those of BMS and are characterised by even less intimal hyperplasia than after a more forceful implantation of SES.

Topics: Aged; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Vessels; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Prosthesis Design; Sirolimus; Stents; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Randomized clinical trials have shown that sirolimus-eluting stents (SESs) decrease restenosis rates compared with bare metal stents (BMSs), but their efficacy among patients who have diabetes mellitus remains to be established. This study investigated the effect of SES implantation in a high-risk population (i.e., patients who had diabetes and small coronary vessel disease). For this purpose, we analyzed outcomes of the subset of patients who had diabetes and were enrolled in the SES-SMART, a randomized trial that compared the results of implantation of SESs and BMSs in small coronary arteries. Twenty-nine patients who had diabetes were originally randomized to receive SESs and 45 patients received BMSs. The use of SESs was associated with approximately 60% decreases in the relative incidence of in-segment angiographic restenosis (63% vs 25%, p = 0.003) and in-segment late loss (0.76 vs 0.28 mm, p <0.002). Angiographic patterns of restenosis were more favorable in the SES group. SES implantation was associated with a 15% absolute decrease in adverse clinical events. In patients who had insulin-dependent diabetes mellitus, SESs showed a high in-segment restenosis rate (40%) that was principally due to persistent restenosis. In conclusion, in diabetics with small coronary arteries, SES implantation significantly reduces the incidence of the 8-month angiographic restenosis rate compared with BMSs.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease-Free Survival; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications; Single-Blind Method; Sirolimus; Stents; Survival Rate; Treatment Outcome

The effectiveness of sirolimus-eluting stents in unselected patients treated in the daily practice is currently unknown.. Sirolimus-eluting stent implantation has been used as the default strategy for all percutaneous procedures in our hospital as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. Consecutive patients with de novo lesions (n=508) treated exclusively with sirolimus-eluting stents (SES group) were compared with 450 patients who received bare stents in the period just before (pre-SES group). Patients in the SES group more frequently had multivessel disease, more type C lesions, received more stents, and had more bifurcation stenting. At 1 year, the cumulative rate of major adverse cardiac events (death, myocardial infarction, or target vessel revascularization) was 9.7% in the SES group and 14.8% in the pre-SES group (hazard ratio [HR], 0.62 [95% CI, 0.44 to 0.89]; P=0.008). The 1-year risk of clinically driven target vessel revascularization in the SES group and in the pre-SES group was 3.7% versus 10.9%, respectively (HR, 0.35 [95% CI, 0.21 to 0.57]; P<0.001).. Unrestricted utilization of sirolimus-eluting stents in the "real world" is safe and effective in reducing both repeat revascularization and major adverse cardiac events at 1 year compared with bare stent implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Female; Heart Diseases; Humans; Male; Netherlands; Registries; Sirolimus; Stents; Treatment Outcome

Patients with diabetes mellitus have less favourable outcomes after percutaneous coronary intervention (PCI) than non-diabetics. We performed a subgroup analysis of the multicentre RAVEL trial to examine the impact of the sirolimus-eluting stent (SES) on outcomes in diabetic patients. The RAVEL study randomized 238 patients to treatment with either sirolimus-eluting or bare metal stents. Forty-four patients were diabetic; 19 received sirolimus-eluting stents and 25 were treated with bare metal stents. The differences in outcomes between diabetic and non-diabetic patients treated with SES (n=101) were also assessed. Follow-up angiography was performed at 6 months. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), or target lesion revascularization (TLR) were analysed at 12-month follow-up. Six-month in-stent late lumen loss was significantly lower for the diabetic SES than the bare stent group (0.07+/-0.2 vs 0.82+/-0.5mm; P<0.001) and similar to that in non-diabetics treated with SES (-0.03+/-0.27mm). There was zero restenosis in the SES groups (diabetic and non-diabetic) compared to a 42% rate in the diabetic population assigned to bare metal stents (P=0.001). After 12 months, there was one non-Q-wave MI and one non-cardiac death in the diabetic SES group, while 12 patients in the bare metal stent group had MACE (one death, two MI, nine TLR) (P=0.01)-an event-free survival rate of 90% vs 52%, respectively (P<0.01). There were no TLRs in both SES groups compared to 36% rate in the diabetic bare metal stent group (P=0.007). Conclusion Diabetics treated with SES were associated with a virtual abolition of neointimal proliferation and low event rates at long-term follow-up.

Topics: Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Stents; Tunica Intima

This study evaluated a large group of patients enrolled in a double-blind randomized trial of the sirolimus-eluting stent to document whether the initial clinical improvement seen in previous smaller series is maintained out to 12 months and to study the potential treatment effect in patient subsets known to be at increased risk of restenosis.. A total of 1058 patients with de novo native coronary stenosis undergoing clinically indicated percutaneous coronary intervention were randomly assigned to sirolimus-eluting stent (533) or control bare stent (525). Procedural success and in-hospital outcomes were excellent and did not differ between the 2 groups. At 9 months, clinical restenosis, defined as target-lesion revascularization, was 4.1% in the sirolimus limb versus 16.6% in the control limb (P<0.001). At 12 months, the absolute difference in target-lesion revascularization continued to increase and was 4.9% versus 20% (P<0.001). There were no differences in death or myocardial infarction rates. In high-risk patient subsets, defined by vessel size, lesion length, and presence of diabetes mellitus, there was a 70% to 80% reduction in clinical restenosis at 1 year.. Placement of the sirolimus-eluting stent results in continued clinical improvement at 1 year after initial implantation, with significant reduction in clinical restenosis as defined by target-lesion revascularization. Between 9 and 12 months, the absolute reduction of clinical restenosis continues to increase. Even in high-risk subsets of patients, there is a 70% to 80% relative reduction in clinical restenosis at 12 months with this drug-eluting stent.

Topics: Coronary Restenosis; Disease-Free Survival; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk Factors; Sirolimus; Stents; Treatment Outcome

The RAVEL and SIRIUS studies have demonstrated important reductions in clinical and angiographic restenosis in lesions treated with sirolimus-eluting stents. However, inclusion criteria in both studies excluded complex lesions. We studied immediate and long-term results with this stent in these complex lesions.. Prospective, observational study with clinical and angiographic follow-up of patients who met the exclusion criteria used in the RAVEL and SIRIUS studies. All patients were treated in our catheterization laboratory between June 2002 and April 2003 with the Cypher stent, and 57 patients (68 lesions) were studied in all. The most frequent lesion characteristics were excessive length 26.5%; ostial lesions 25%, bifurcations 23.5%, and severe calcifications 22.1%. Almost half (47%) of the patients had diabetes and 68% had multivessel disease.. PTCA was successful in all patients. There was one major adverse cardiovascular event (MACE) before discharge (1 acute Q-wave myocardial infarction). Two episodes of subacute thrombosis occurred during the first week. During long-term clinical follow-up (8.7 [3.1] months) of all patients, there were 4 MACE (7%): 1 cardiac death, 1 acute myocardial infarction and 2 revascularizations of the target vessel. Intersegmental restenosis was observed by angiography in 4 lesions (8%).. Implantation of the Cypher stent in complex lesions is safe and is associated, after 6 months of follow-up, with a low incidence of clinical events and a very low percentage of angiographic restenosis.

Topics: Adult; Aged; Combined Modality Therapy; Coronary Restenosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Revascularization; Prospective Studies; Radiography; Sirolimus; Stents

Sirolimus-eluting stents have been shown to be effective in de-novo coronary lesions, reducing restenosis strikingly in a subset of lesions with a low or moderate risk of restenosis. We decided to assess their usefulness in lesions with a high risk of restenosis.. We included consecutive patients with lesions that met at least one of the following criteria: a) in-stent restenosis; b) diffuse lesion (>20 mm); c) small vessel (< or =2.5 mm), and d) total occlusion.. Between June 2002 to December 2002, 100 patients were included (61 [11] years, 84% men, 21% with diabetes). In all, 154 lesions were treated (34% diffuse lesions, 36% in small vessels, 20% in-stent restenosis and 20% occlusions). An average of 1.6 (0.7) stents were implanted per patient. Mean diameter was 2.74 (0.26) mm, mean length was 21 (8.5) mm and total stent length per patient was 33 (16) mm. The acute success rate was 98%. After the procedure 2 (2%) non-Q-wave infarctions were diagnosed. No episodes of acute or subacute thrombosis occurred. During a follow-up period of 8.5 (2) months (range 6-12 months) there were two (2%) late thromboses, one of which caused an infarction. Target lesion revascularization was required in 3 patients (3%), two of whom were the patients with late thrombosis.. Sirolimus-eluting stents can be used in lesions with a high risk of restenosis. The rate of thrombosis was low, and the use of these stents was associated with a strikingly low rate of target lesion revascularization during follow-up.

Topics: Combined Modality Therapy; Coronary Restenosis; Coronary Stenosis; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk Factors; Sirolimus; Stents; Time Factors

This study investigated the clinical outcomes of patients with ST-segment elevation myocardial infarction (MI) treated with sirolimus-eluting stents (SESs) or with conventional bare stents.. The clinical impact of SES implantation for patients with ST-segment elevation MI is currently unknown.. Primary angioplasty was performed with SESs in 186 consecutive patients with acute MI who were compared with 183 patients treated with bare stents. The incidence of death, reinfarction, and repeat revascularization was assessed at 30 and 300 days.. Postprocedure vessel patency, enzymatic release, and the incidence of short-term adverse events were similar in both the sirolimus and the bare stents (30-day rate of death, reinfarction, or repeat revascularization: 7.5% vs. 10.4%, respectively; p = 0.4). Stent thrombosis was not diagnosed in any patient in the sirolimus group and occurred in 1.6% of patients treated with bare stents (p = 0.1). At 300 days, treatment with SESs significantly reduced the incidence of combined adverse events (9.4% vs. 17%; hazard ratio [HR] 0.52 [95% confidence interval (CI) 0.30 to 0.92]; p = 0.02), mainly due to a marked reduction in the risk of repeat intervention (1.1% vs. 8.2%; HR 0.21 [95% CI 0.06 to 0.74]; p = 0.01).. Compared to conventional bare stents, the SESs were not associated with an increased risk of stent thrombosis and were effective in reducing the incidence of adverse events at 300 days in unselected patients with ST-segment elevation acute MI referred for primary angioplasty.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Sirolimus; Stents; Time Factors; Treatment Outcome

A sirolimus-eluting stent (Cypher, Cordis Corp) has been reported to markedly decrease restenosis in selected lesions; higher-risk lesions, including coronary bifurcations, have not been studied.. This prospective study evaluated the safety and efficacy of sirolimus-eluting stents for treatment of coronary bifurcation lesions. Patients were randomly assigned to either stenting of both branches (group A) or stenting of the main branch with provisional stenting of the side branch (SB) (group B). Eighty-five patients (86 lesions) were enrolled. There was 1 case of unsuccessful delivery of any device at the bifurcation site. Given the high crossover, more lesions were treated with 2 stents (n=63) than with stent/balloon (n=22). Clinical follow-up at 6 months was completed in all patients and angiographic follow-up in 53 patients in group A (85.5%) and 21 in group B (95.4%). One patient died suddenly 4.5 months after the procedure. There were 3 cases of stent thrombosis (3.5%). The total restenosis rate at 6 months was 25.7%, and it was not significantly different between the double-stenting (28.0%) and the provisional SB-stenting (18.7%) groups. Fourteen of the restenosis cases occurred at the ostium of the SB and were focal. Target lesion revascularization was performed in 7 cases; target vessel failure occurred in 15 cases (17.6%).. These results are an improvement compared with historical controls using bare metal stents. Restenosis at the SB remains a problem. At this time, no statement can be made regarding the most appropriate technique to use when treating bifurcations with the Cypher stent.

Topics: Aged; Anticoagulants; Aspirin; Catheterization; Clopidogrel; Combined Modality Therapy; Comorbidity; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Death, Sudden; Diabetes Mellitus; Disease-Free Survival; Drug Implants; Female; Follow-Up Studies; Humans; Life Tables; Male; Middle Aged; Pilot Projects; Postoperative Complications; Prospective Studies; Safety; Sirolimus; Stents; Survival Analysis; Ticlopidine; Treatment Outcome

We used intravascular ultrasound (IVUS) to evaluate recurrence after sirolimus-eluting stent (SES) implantation treatment of in-stent restenosis (ISR).. Forty-eight ISR lesions (41 patients with objective evidence of ischemia) were treated with SES. Recurrent ISR was identified in 11 lesions (all focal); repeat revascularization was performed in 10. These were compared with 16 patients (19 lesions) without recurrence as documented by angiography. Nine of 11 recurrent lesions had a minimum stent area (MSA) <5.0 mm2 versus 5 of 19 nonrecurrent lesions (P=0.003); 7 of 11 recurrent lesions had an MSA <4.0 mm2 versus 4 of 19 nonrecurrent lesions (P=0.02); and 4 of 11 recurrent lesions had an MSA <3.0 mm2 versus 1 of 19 nonrecurrent lesions (P=0.03). A gap between SESs was identified in 3 of 11 recurrences versus 1 of 19 nonrecurrent lesions.. Stent underexpansion is a significant cause of failure after SES implantation treatment of ISR.

Topics: Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Sirolimus; Stents; Treatment Failure; Ultrasonography

Percutaneous coronary intervention in patients with a history of previous coronary artery bypass grafting (CABG) is associated with an increased rate of subsequent adverse events compared to those without prior CABG. We evaluated the impact of utilizing the sirolimus-eluting stent (SES) in this high-risk population.. Since April 2002, SES implantation was utilized as the default strategy for all percutaneous procedures in our hospital. Consecutive patients with a history of previous CABG and de novo lesions (n=47) treated exclusively with SES, were compared to 66 patients who received bare stents in the 6-month period just before SES introduction.. There were no significant differences between the groups (SES and bare stent) with respect to baseline clinical or lesion characteristics. The only difference between the groups related to the nominal diameter of stent utilized, which was smaller in the SES group than the bare stent group. (The maximum diameter of SES available was 3.0 mm). At 1 year, the cumulative incidence of major adverse events (defined as death, myocardial infarction, or target vessel revascularization) was significantly lower in the SES group than the bare stent group [8.5 versus 30.3%, hazard ratio 0.37 (95% confidence interval 0.15-0.91); P=0.03].. The utilization of the sirolimus-eluting stent for percutaneous intervention in a high-risk population with a history of previous CABG surgery is associated with a significant reduction in the rate of major adverse cardiac events at 1 year.

Topics: Aged; Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Female; Humans; Immunosuppressive Agents; Male; Netherlands; Sirolimus; Stents; Treatment Outcome

Randomized clinical trials have shown that a sirolimus-eluting stent significantly reduces restenosis after percutaneous coronary revascularization. Diabetic patients are known to have a higher risk of restenosis compared with nondiabetic patients. The purpose of this analysis was to determine the impact of sirolimus-eluting stents on outcomes of diabetic compared with nondiabetic patients.. The SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) trial is a randomized, double-blind study that compared sirolimus-eluting and bare metal stent implantation in 1058 patients with de novo native coronary artery lesions. Diabetes mellitus was present in 279 (26%) patients (diabetes mellitus group, 131 patients received sirolimus-eluting stents and 148 patients received bare metal stents) and was absent in 778 patients (no-diabetes mellitus group, 402 patients received sirolimus-eluting stents and 376 patients received bare metal stents). At 270 days, target lesion revascularization was reduced in diabetic patients from 22.3% with bare metal stents to 6.9% with sirolimus-eluting stents (P<0.001) and in nondiabetic patients from 14.1% to 2.99% (P<0.001), respectively. Major adverse cardiac events were reduced in diabetic patients from 25% with bare metal stents to 9.2% with sirolimus-eluting stents (P<0.001) and from 16.5% to 6.5% (P<0.001) in nondiabetic patients, respectively.. Implantation of sirolimus-eluting stents compared with bare metal stents in de novo coronary lesions reduces major adverse cardiac events in patients with and without diabetes mellitus. However, among patients receiving sirolimus-eluting stents, there remains a trend toward a higher frequency of repeat intervention in diabetic patients compared with nondiabetic patients, particularly in the insulin-requiring patients.

Topics: Aged; Anticoagulants; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Diabetes Mellitus; Disease-Free Survival; Double-Blind Method; Drug Implants; Female; Follow-Up Studies; Growth Inhibitors; Humans; Hypertension; Immunosuppressive Agents; Incidence; Insulin; Male; Middle Aged; Mortality; Myocardial Infarction; Sirolimus; Stents; Treatment Outcome

Everolimus, an active immunosuppressive and antiproliferative agent of the same family as sirolimus (rapamycin), has demonstrated significant reduction of neointimal proliferation in animal studies. The First Use To Underscore restenosis Reduction with Everolimus (FUTURE) I trial was the first in-human experience to evaluate the safety and efficacy of everolimus-eluting stents (EES), coated with a bioabsorbable polymer, compared with bare metal stents (BMS).. FUTURE I was a prospective, single-blind, randomized trial that enrolled 42 patients with de novo coronary lesions (EES 27, BMS 15). Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low at 30 days and 6 months, without any early or late stent thrombosis for either group (P=NS). Between 6 and 12 months, there were no additional reports of major adverse cardiac events. The 6-month angiographic in-stent restenosis rate was 0% versus 9.1% (1 patient) (P=NS), with an associated late loss of 0.11 mm versus 0.85 mm (P<0.001), and the in-segment restenosis rate was 4% (1 patient) and 9.1% (1 patient) (P=NS) for EES and BMS, respectively. Intravascular ultrasound analysis revealed a significant reduction of percent neointimal volume in EES compared with BMS (2.9+/-1.9 mm3/mm versus 22.4+/-9.4 mm3/mm, P<0.001). There was no late stent malapposition in either group. The safety and efficacy of the EES appeared to be sustained at 12 months.. In this initial clinical experience, EES with bioabsorbable polymer demonstrated a safe and efficacious method to reduce in-stent neointimal hyperplasia and restenosis.

Topics: Aged; Anticoagulants; Catheterization; Cineangiography; Coated Materials, Biocompatible; Comorbidity; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug Implants; Everolimus; Female; Follow-Up Studies; Growth Inhibitors; Humans; Hyperplasia; Immunosuppressive Agents; Lactic Acid; Male; Middle Aged; Myocardial Infarction; Polyesters; Polymers; Prospective Studies; Single-Blind Method; Sirolimus; Stainless Steel; Stents; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Primary bare metal stenting and abciximab infusion are currently considered the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus eluting stents (SES), compared to bare metal stent (BMS), greatly reduce the incidence of binary restenosis and target vessel revascularisation (TVR), but their use on a routine basis results in a significant increase in medical costs. With current European list prices, the use of tirofiban instead of abciximab would save enough money to absorb the difference between SES and BMS.. To assess whether in patients with STEMI the combination of SES with high dose bolus (HDB) tirofiban results in a similar incidence of major cardiovascular events (MACE) but in a lower binary restenosis rate after six months compared to BMS and abciximab.. 160 patients are required to satisfy the primary composite end-point, including MACE and binary restenosis. The study is ongoing: the current paper focuses on the methodology and demography of the first 100 patients so far enrolled. Patients randomised to HDB tirofiban (n = 50, mean age: 62 +/- 12, 40 males) and abciximab (n = 50, mean age: 63 +/- 12, 38 males) do not differ for medical history, presentation profile, medications at discharge, angiographic profile and creatine-kinase MB-fraction at peak.. The results of the trial will be available by the end of 2004: they will be crucial for the cardiologists to know whether the gold standard for AMI treatment should be reconsidered after the introduction of SES into the clinical practice.

Topics: Abciximab; Antibodies, Monoclonal; Clinical Protocols; Coronary Restenosis; Drug Implants; Drug Therapy, Combination; Electrocardiography; Female; Forecasting; Humans; Immunoglobulin Fab Fragments; Injections; Italy; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation; Sirolimus; Stents; Time Factors; Tirofiban; Treatment Outcome; Tyrosine

Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the "reintervention gap" between surgery and percutaneous intervention, making the percutaneous route preferable.. Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P<0.001). One-year major adverse events (defined as cardiac death, Q-wave and non-Q-wave myocardial infarction, or target vessel revascularization) was decreased 59% in the sirolimus-stent group (9.8% versus 24.9%; relative risk, 0.39; 95% CI, 0.26 to 0.61; P<0.001). Subgroup analysis of 135 patients with proximal LAD lesions showed similar benefits. In-stent restenosis was 0 in the proximal LAD sirolimus-eluting group (n=67), compared with 38% in the bare-metal arm (n=68), and major adverse events demonstrated a similar trend, with a 50% decrease compared with control patients (10.4% versus 20.6%, P=NS).. Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Double-Blind Method; Drug Implants; Female; Humans; Life Tables; Male; Middle Aged; Myocardial Infarction; Premedication; Sirolimus; Stents; Survival Analysis; Ticlopidine; Treatment Outcome; Ultrasonography

Recently, sirolimus-eluting stents (SESs) have been shown to dramatically reduce the risk of angiographic and clinical restenosis compared with bare metal stent (BMS) implantation. However, the overall cost-effectiveness of this strategy is unknown.. Between February and August 2001, 1058 patients with complex coronary stenoses were enrolled in the SIRIUS trial and randomized to percutaneous coronary revascularization with either a SES or BMS. Clinical outcomes, resource use, and costs were assessed prospectively for all patients over a 1-year follow-up period. Initial hospital costs were increased by 2881 dollars per patient with SESs. Over the 1-year follow-up period, use of SESs led to substantial reductions in the need for repeat revascularization, including repeat percutaneous coronary intervention and bypass surgery. Although follow-up costs were reduced by 2571 dollars per patient with SESs, aggregate 1-year costs remained 309 dollars per patient higher. The incremental cost-effectiveness ratio for SES was 1650 dollars per repeat revascularization event avoided or 27,540 dollars per quality-adjusted year of life gained, values that compare reasonably with other accepted medical interventions. Under updated treatment assumptions regarding available stent lengths and duration of antiplatelet therapy, use of SESs was projected to reduce total 1-year costs compared with BMSs.. Although use of SESs was not cost-saving compared with BMS implantation, for patients undergoing percutaneous coronary intervention of complex coronary stenoses, their use appears to be reasonably cost-effective within the context of the US healthcare system.

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheterization; Clopidogrel; Coronary Restenosis; Cost-Benefit Analysis; Diabetes Mellitus; Double-Blind Method; Drug Costs; Equipment Design; Female; Follow-Up Studies; Health Care Costs; Health Resources; Hospital Costs; Humans; Male; Middle Aged; Myocardial Revascularization; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Sirolimus; Stents; Ticlopidine; Treatment Outcome; United States

Despite recent advances in interventional cardiology, including the introduction of drug-eluting stents for de novo coronary lesions, the treatment of in-stent restenosis (ISR) remains a challenging clinical issue. Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR.. Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms: placebo or usual-dose or high-dose sirolimus. Patients received a cumulative loading dose of 0, 8, or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days. Angiographic restenosis at 6-month angiography was the primary end point of the study. Restenosis was significantly reduced from 42.2% to 38.6% and to 22.1% in the placebo, usual-dose, and high-dose sirolimus groups, respectively (P=0.005). Similarly, the need for target vessel revascularization was reduced from 25.5% to 24.2% and to 15.2% in the placebo, usual-dose, and high-dose groups, respectively (P=0.08). The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up (P<0.001).. In patients with ISR, an oral adjunctive sirolimus treatment with an intensified loading regimen before coronary intervention resulted in a significant improvement in the angiographic parameters of restenosis.

Topics: Administration, Oral; Aged; Angioplasty, Balloon, Coronary; Biomarkers; Comorbidity; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Creatine Kinase; Creatine Kinase, MB Form; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Retreatment; Sirolimus; Stents; Treatment Outcome; Tunica Intima

Recent human trials with rapamycin-eluting stents have shown very low restenosis rates. However, the high costs of these devices preclude their use in routine angioplasty, especially when considering multiple stenting. We evaluated whether orally administered rapamycin inhibits in-stent neointimal growth in patients with unstable angina.. We enrolled 15 patients successfully treated with the implantation of a single stent in a single de novo lesion in native coronary arteries. Correct stent expansion and apposition were corroborated with intravascular ultrasound scanning in all patients. Patients received aspirin, clopidogrel, and atorvastatin for 6 months. Rapamycin was administered in a loading dose of 5 mg, followed by 2 mg/day for 4 weeks.. The reference diameter was 3.4 +/- 0.4 mm, lesion length was 11.2 +/- 2 mm, lesion type B1 was 36%, and lesion type B2 was 64%. After the procedure, in-stent minimal lumen diameter and diameter stenosis (DS) were 3.3 +/- 0.4 mm and 0.3% +/- 7.5%, respectively. At 10 days, plasma levels of rapamycin were 7.95 +/- 2.6 ng/mL. At 6 months, angiographic determinations demonstrated an in-stent minimal lumen diameter of 2 +/- 1 mm, an in-stent DS of 41.3% +/- 28.0%, and an in-stent late loss of 1.4 +/- 1.1 mm. Binary restenosis (>50% DS) was present in 6 of 15 patients (40%). Target lesion revascularization (coronary artery bypass grafting) was performed in 2 of 15 patients (13.3%). There were no serious adverse events during the 6-month period of follow-up, but 1 patient had severe heartburn caused by esophagitis, and another patient had herpes zoster at the end of the protocol.. Oral rapamycin was well tolerated, but did not suppress in-stent neointimal growth in this small group of patients.

Topics: Administration, Oral; Angina, Unstable; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Humans; Immunosuppressive Agents; Pilot Projects; Sirolimus; Stents; Tunica Intima

Topics: Adult; Aged; Aged, 80 and over; Coronary Restenosis; Cost-Benefit Analysis; Drug Implants; Female; Humans; Immunosuppressive Agents; Length of Stay; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Sirolimus; Stents; Survival Analysis; Treatment Outcome

The aim of this study was to establish safety and feasibility of oral Rapamycin at two doses-2 mg and 5 mg-in achieving low rates of repeat target lesion revascularization (TLR) in de novo native coronary artery lesions.. Drug-eluting stents have shown the ability to limit restenosis. Oral Rapamycin is an alternative strategy that can target multiple coronary lesions suitable for treatment with any approved metal stent and at potentially lower cost.. The Oral Rapamune to Inhibit Restenosis (ORBIT) study is an open-label study of 60 patients with de novo lesions treated with bare metal stents in up to two vessels. After a loading dose of 5 mg, patients received a daily dose of 2 mg (n = 30) and 5 mg (n = 30) for 30 days. Six-month angiographic, intravascular ultrasound (IVUS), and clinical follow-up were conducted.. Baseline clinical and procedural characteristics were similar: 10% of patients in the 2-mg group and 30% in the 5-mg group did not complete the course; 43% in the 2-mg group and 66% in the 5-mg group had side effects. At six-month follow-up, late loss (0.6 +/- 0.5 mm vs. 0.7 +/- 0.5 mm; p = NS), in-stent binary restenosis (7.1% vs. 6.9%; p = NS), in-stent percent volume obstruction by IVUS (29% vs. 24%; p = NS), and clinically driven TLR (14.3% vs. 6.9%; p = NS) were similar in 2-mg and 5-mg groups.. Oral Rapamycin for the prevention of restenosis is safe, feasible, and associated with low rates of repeat revascularization. Although associated with certain side effects, it may be considered for patients undergoing multivessel stents if proven in larger randomized studies.

Topics: Administration, Oral; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

Rapamycin-eluting stents (RES) have been shown to reduce restenosis in many types of lesions. However, the ideal strategy for the treatment of coronary bifurcated lesions has not been established to date. This randomized study compares 2 strategies for the RES treatment of bifurcation lesions: a simple approach (stenting the main vessel and balloon dilatation for the side branch [SB]) versus a complex approach (stents for both vessels).. To compare both strategies, a randomized study was conducted in 91 patients with true coronary bifurcation lesions. All patients received an RES at the main vessel, covering the SB. Patients from group A (n = 47) were assigned to balloon dilation of the involved SB (simple strategy); patients in group B (n = 44) were randomized to receive a second stent at the SB origin (complex strategy). There were no differences between groups regarding baseline clinical and angiographic data.. Major adverse cardiac events occurred in 3 patients from group A (2 non-Q-wave myocardial infarctions and 1 target lesion revascularization). Six-month angiographic reevaluation was obtained in 80 patients (88%). Restenosis of the main vessel was observed in 1 (2%) patient from group A and in 4 (10%) from group B. Restenosis of the SB appeared in 2 (5%) patients from group A and in 6 (15%) from group B.. Both strategies are effective in reducing the restenosis rate, with no differences in terms of clinical outcome. Elective SB stenting seems to provide no advantages over the simpler stent jail followed by SB balloon dilation.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Cross-Over Studies; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Stents; Treatment Outcome

Despite the growing use of drug-eluting stents, restenosis remains to occur especially in high risk subgroups like patients with diffuse in-stent restenosis. This observation is supporting the search for new and potentially even more effective drug eluting stent systems. Everolimus has been used in conjunction with a new bioabsorbable polymer and gave promising results in initial clinical studies. In FUTURE I, a single-center, single-blinded randomized safety and feasibility study enrolling 15 patients with bare metal stents and 27 patients with everolimus-coated stents, 30-day MACE rate was 0% in both groups. In-stent late loss at six months was 0.83 mm in the control group and 0.10 mm in the everolimus group (p < 0.0001). In FUTURE II, a randomized multi-center study, a total of 64 patients were enrolled confirming safety and feasibility. After 6 months late loss was 0.85 mm in the control group and 0.12 mm in the everolimus group (p < 0.001).

Topics: Coronary Disease; Coronary Restenosis; Everolimus; Humans; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Sirolimus; Stents

Percutaneous coronary revascularization of small vessels is associated with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in simple and previously untreated lesions of large coronary arteries, but their outcomes in small vessels have not been adequately investigated.. To determine whether sirolimus-eluting stents are associated with a reduced 8-month rate of angiographic restenosis in comparison with an uncoated stent.. This was a randomized, multicenter, single-blind, prospective trial performed with 257 patients undergoing percutaneous coronary revascularization for ischemic heart disease, and who had a previously untreated atherosclerotic lesion located in a small segment with a diameter of 2.75 mm or less, in 20 Italian centers between August 2002 and December 2003.. Patients were randomly assigned to receive a sirolimus-eluting stent (129 patients) or an uncoated stent having an identical architecture and radiographic appearance (128 patients).. The primary end point was the 8-month binary in-segment restenosis rate; secondary end points included procedural success and the 8-month rate of major adverse cardiac and cerebrovascular events.. The mean (SD) reference diameter of the treated segment was 2.2 (0.28) mm; the lesion length, 11.84 (6.15) mm. After 8 months, the binary in-segment restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk [RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001). Fewer patients randomized to sirolimus-eluting stents experienced major adverse cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P = .002) and myocardial infarction (2/129 [1.6%] vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P = .04).. The use of sirolimus-eluting stents to treat atherosclerotic lesions in small coronary arteries reduces restenosis and may also reduce major adverse cardiac events.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Radiography; Single-Blind Method; Sirolimus; Stents

Sirolimus-eluting stents (SESs) reduce angiographic restenosis in patients with focal, native coronary artery stenoses. This study evaluated the usefulness of SESs in complex native-vessel lesions at high risk for restenosis.. Angiographic follow-up at 240 days was obtained in 701 patients with long (15- to 25-mm) lesions in small-diameter (2.5- to 3.5-mm) native vessels who were randomly assigned to treatment with SESs or bare-metal stents (BMSs) in the SIRIUS trial. Quantitative angiographic measurements of minimal lumen diameter and percent diameter stenosis were obtained within the treated segment, within the stent, and within its 5-mm proximal and distal edges. Patients treated with SESs had lower rates of binary (>50% diameter stenosis) angiographic restenosis within the segment (8.9% versus 36.3% with the BMS; P<0.001) and within the stent (3.2% versus 35.4% with the BMS; P<0.001). SESs were associated with significantly less late lumen loss within the treated segment, within the stent, and within its 5-mm proximal and distal edges (all P<0.001). The reduction of restenosis with the SES was consistent in patients at risk for restenosis, including those with small vessels, long lesions, and diabetes mellitus. The frequency of late aneurysms was similar in the 2 groups.. Compared with BMSs, SESs reduced angiographic late lumen loss within the stent and its adjacent 5-mm margins in patients with complex native-vessel lesions.

Topics: Aged; Aspirin; Clopidogrel; Coronary Aneurysm; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Double-Blind Method; Drug Implants; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Humans; Incidence; Male; Middle Aged; Randomized Controlled Trials as Topic; Sirolimus; Stents; Ticlopidine; Treatment Outcome

Given the encouraging results on early restenosis rate with drug-eluting coronary stents, both safety and 6 months outcomes of PCI with sirolimus-eluting stents (SES) in acute myocardial infarction are scarce.. Fifty consecutive patients with acute myocardial infarction were subjected to acute PCI with SES and compared to 50 matched control patients who received a bare metal stent (BMS). All patients were followed over 6 months; in addition repeat angiography was obtained in 88.0% of SES and 92.0% of BMS patients. As a result of matching both groups were similar with regard to demographic, clinical, and infarction characteristics, as well as procedural data and adjunctive medication. SES diameter was 3.0 +/- 0.1 versus 3.3 +/- 0.5 mm with BMS, while the length of stented segment was 24 +/- 11 mm with SES versus 16 +/- 8 mm with BMS (p<0.05). No subacute stent thrombosis occurred in either group. At 6 months, all-cause mortality was 2.0% with SES, and 4.0% with BMS (n. s.); reinfarction rate was 2.0% in both groups, but binary restenosis rate (4.0 versus 18.0%; p<0.05) and target vessel revascularization (TVR) were improved with SES (2.0 versus 16.0%; p<0.05) resulting in lower MACE rate of 6.0 versus 22.0% with BMS (p<0.05).. Placement of SES with PCI for myocardial infarction is feasible and as safe as BMS; 6-month outcome is superior with SES due to the lower rate of both angiographic restenosis and TVR.

Topics: Aged; Angioplasty, Balloon, Coronary; Case-Control Studies; Coated Materials, Biocompatible; Cohort Studies; Coronary Angiography; Coronary Restenosis; Device Approval; Equipment Safety; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

We have previously reported the safety and effectiveness of sirolimus-eluting stents for the treatment of de novo coronary lesions. The present investigation explored the potential of this technology to treat in-stent restenosis.. Twenty-five patients with in-stent restenosis were successfully treated with the implantation of 1 or 2 sirolimus-eluting Bx VELOCITY stents in São Paulo, Brazil. Nine patients received 2 stents (1.4 stents per lesion). Angiographic and volumetric intravascular ultrasound (IVUS) images were obtained after the procedure and at 4 and 12 months. All vessels were patent at the time of 12-month angiography. Angiographic late loss averaged 0.07+/-0.2 mm in-stent and -0.05+/-0.3 mm in-lesion at 4 months, and 0.36+/-0.46 mm in-stent and 0.16+/-0.42 mm in-lesion after 12 months. No patient had in-stent or stent margin restenosis at 4 months, and only one patient developed in-stent restenosis at 1-year follow-up. Intimal hyperplasia by 3-dimensional IVUS was 0.92+/-1.9 mm(3) at 4 months and 2.55+/-4.9 mm(3) after 1 year. Percent volume obstruction was 0.81+/-1.7% and 1.76+/-3.4% at the 4- and 12-month follow-up, respectively. There was no evidence of stent malapposition either acutely or in the follow-up IVUS images, and there were no deaths, stent thromboses, or repeat revascularizations.. This study demonstrates the safety and the potential utility of sirolimus-eluting Bx VELOCITY stents for the treatment of in-stent restenosis.

Topics: Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Delayed-Action Preparations; Echocardiography, Three-Dimensional; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Secondary Prevention; Sirolimus; Stents

The safety and efficacy of sirolimus-eluting stenting have been demonstrated, but the outcome of patients treated with this novel technology beyond the first year remains unknown. We sought to evaluate the angiographic, intravascular ultrasound (IVUS), and clinical outcomes of patients treated with sirolimus-eluting stents 2 years after implantation.. This study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR], n=15, and fast release [FR], n=15) in São Paulo, Brazil. Twenty-eight patients underwent 2-year angiographic and IVUS follow-up. No deaths occurred during the study period. In-stent late loss was slightly greater in the FR group (0.28+/-0.4 mm) than in the SR group (-0.09+/-0.23 mm, P=0.007). No patient had in-stent restenosis. At 2-year follow-up, only 1 patient (FR group) had a 52% diameter stenosis within the lesion segment, which required repeat revascularization. The target-vessel revascularization rate for the entire cohort was 10% (3/30) at 2 years. All other patients had < or =35% diameter stenosis. Angiographic lumen loss at the stent edges was also minimal (in-lesion late loss was 0.33+/-0.42 mm [FR] and 0.13+/-0.29 mm [SR]). In-stent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 2 years (FR= 9.90+/-9 mm3 and SR=10.35+/-9.3 mm3).. This study demonstrates the safety and efficacy of sirolimus-eluting Bx Velocity stents 2 years after implantation in humans. In-stent lumen dimensions remained essentially unchanged at 2-year follow-up in the 2 groups, although angiographic lumen loss was slightly higher in the FR group. Restenosis "catch-up" was not found in our patient population.

Topics: Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Delayed-Action Preparations; Follow-Up Studies; Humans; Sirolimus; Stents; Treatment Outcome; Ultrasonography

Sirolimus-coated stents are a promising new therapy for restenosis. We treated a select group of patients at especially high risk for restenosis with oral sirolimus.. Patients were treated with an oral sirolimus-loading dose of 6 mg after coronary angioplasty, followed by 2 mg/d for 4 weeks. Serum electrolytes, lipid profile, renal panel, and complete blood cell count were measured at 1, 3, and 5 weeks after drug initiation. Oral sirolimus was prescribed to 22 patients who had a total of 28 lesions and were at high risk for restenosis. Of the 22 study patients, 11 (50%) discontinued oral sirolimus early because of side effects or laboratory abnormalities. Hypertriglyceridemia and leukopenia were the most frequent adverse events, occurring in 3 patients each. All adverse drug effects were reversible after discontinuation. Follow-up was obtained in 100% of patients at a mean of 9.9+/-1.8 months, ranging from 6.5 to 11.8 months. Target lesion revascularization (TLR) occurred in 15 of 28 lesions (53.6%) and 13 of 22 patients (59.1%). There was no difference in TLR for patients receiving a complete course of sirolimus (n=8; 72.7%) compared with patients who terminated treatment prematurely (n=5; 45.5%; P=NS). Clinically driven repeat cardiac catheterization was obtained in 15 (68.2%) patients; restenosis (>50% diameter stenosis at follow-up) was present in 13 (86.7%).. Oral sirolimus does not appear to provide benefit to patients with recalcitrant restenosis. Adverse drug effects are frequent, underscoring the importance of local drug delivery to achieve high tissue concentrations without systemic adverse drug effects.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Sirolimus; Stents; Treatment Failure

Restenosis after implantation of drug-eluting stents (DES) is a rare phenomenon, occurring more frequently peri-stent.. We evaluated the pattern of restenosis occurring after implantation of DES in unselected lesions. From April 15 to December 6, 2002, we treated 368 patients with 735 lesions by using 841 rapamycin-eluting stents (Cypher, Cordis, a Johnson & Johnson Company). Mean baseline lesion length was 17.48+/-12.19 mm, and mean stent length was 27.59+/-14.02 mm. Follow-up ischemia-driven angiography was performed in 24 patients. Eleven patients had angiographic restenosis (> or =50% diameter stenosis) in 14 stented segments (stent and 5 mm proximal and distal to the stent). The pattern of restenosis in all 14 stented segments was focal, and in 6 of them it was multifocal, occurring inside the stents. Mean length of restenotic lesions was 5.62+/-1.90 mm, with a range from 2.54 to 8.44 mm. One multifocal restenosis involved also the distal stent margin. Intravascular ultrasound evaluation at follow-up, performed in 2 patients, showed significant lumen obstruction attributable to in-stent hyperplasia in both cases. Individual cases can be viewed in the Data Supplement.. The pattern of restenotic lesions after rapamycin-eluting stent implantation was focal and mostly inside the stent.

Topics: Aged; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Follow-Up Studies; Humans; Male; Middle Aged; Sirolimus; Stents

FIM STUDY: We investigated the 2-year safety and efficacy of sirolimus-eluting stents. Thirty patients had a single 18-mm sirolimus-eluting coronary stent implanted. Twenty-eight patients underwent angiographic and intravascular ultrasound follow-up at 2 years. No death occurred during the study period. No patient developed in-stent restenosis. One patient had a 52% in-lesion stenosis that required repeated revascularization and another patient underwent target vessel revascularization. Neointimal hyperplasia volume was minimal at 2 years in both groups. This study demonstrates the 2-year safety and efficacy of sirolimus-eluting stenting. The slow release formulation showed slight superiority over the fast-release formulation in preventing late lumen loss, which was minimal in both groups.. This-study was a randomized, double-blind study that included 238 patients at 19 medical centers (15 in Europe, 3 in Brazil, and 1 in Mexico). Patients were eligible for the study if they were between 18 and 85 years of age, and had been given a diagnosis of stable or unstable angina or silent ischemia. Additional eligibility criteria were presence of a single primary target lesion in a native coronary artery that was 2.5 to 3.5 mm in diameter and that could be covered by an 18-mm stent stenosis of 51% to 99% of the luminal diameter and a flow rate of grade 1 or higher according to the Thrombolysis in Myocardial Infarction.. One hundred twenty patients were randomly assigned to receive the sirolimus-eluting stent, and 118 were assigned to receive the standard stent. At 6 months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01 +/- 0.33 mm) than in the standard-stent group (0.80 +/- 0.53 mm, P <.001). None of the patients in the sirolimus-stent group, as compared with 26.6% of those in the standard-stent group, had restenosis of >/=50% of the luminal diameter (P <.001). There were no episodes of stent thrombosis. During a follow-up period of up to 1 year, the overall rate of major cardiac events was 5.8% in the sirolimus-stent group and 28.8% in the standard-stent group (P <.001). The difference was due entirely to the higher rate of revascularization of the target vessel in the standard-stent group.. Patients with angina who received sirolimus-eluting stents for the treatment of single, primary lesions in native coronary arteries had no angiographic evidence of late luminal loss or in-stent restenosis at 6 months, no episodes of thrombosis, and a very low rate of cardiac events at 1 year.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Vessels; Female; Follow-Up Studies; Humans; Hypertension; Immunosuppressive Agents; Male; Middle Aged; Risk Factors; Sirolimus; Smoking; Stents; Time Factors; Treatment Outcome

We describe the clinical and morphological patterns of restenosis after sirolimus-eluting stent (SES) implantation.. From 121 patients with coronary angiography obtained >30 days after SES implantation, restenosis (diameter stenosis >50%) was identified in 19 patients and 20 lesions (located at the proximal 5-mm segment in 30% or within the stent in 70%). Residual dissection after the procedure or balloon trauma outside the stent was identified in 83% of the proximal edge lesions. Lesions within the stent were focal, and stent discontinuity was identified in some lesions evaluated by intravascular ultrasound.. Sirolimus-eluting stent edge restenosis is frequently associated with local trauma outside the stent. In-stent restenosis occurs as a localized lesion, commonly associated with a discontinuity in stent coverage. Local conditions instead of intrinsic drug-resistance to sirolimus are likely to play a major role in post-SES restenosis.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Drug Implants; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Postoperative Complications; Registries; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

Preliminary reports of studies involving simple coronary lesions indicate that a sirolimus-eluting stent significantly reduces the risk of restenosis after percutaneous coronary revascularization.. We conducted a randomized, double-blind trial comparing a sirolimus-eluting stent with a standard stent in 1058 patients at 53 centers in the United States who had a newly diagnosed lesion in a native coronary artery. The coronary disease in these patients was complex because of the frequent presence of diabetes (in 26 percent of patients), the high percentage of patients with longer lesions (mean, 14.4 mm), and small vessels (mean, 2.80 mm). The primary end point was failure of the target vessel (a composite of death from cardiac causes, myocardial infarction, and repeated percutaneous or surgical revascularization of the target vessel) within 270 days.. The rate of failure of the target vessel was reduced from 21.0 percent with a standard stent to 8.6 percent with a sirolimus-eluting stent (P<0.001)--a reduction that was driven largely by a decrease in the frequency of the need for revascularization of the target lesion (16.6 percent in the standard-stent group vs. 4.1 percent in the sirolimus-stent group, P<0.001). The frequency of neointimal hyperplasia within the stent was also decreased in the group that received sirolimus-eluting stents, as assessed by both angiography and intravascular ultrasonography. Subgroup analyses revealed a reduction in the rates of angiographic restenosis and target-lesion revascularization in all subgroups examined.. In this randomized clinical trial involving patients with complex coronary lesions, the use of a sirolimus-eluting stent had a consistent treatment effect, reducing the rates of restenosis and associated clinical events in all subgroups analyzed.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Coronary Stenosis; Diabetes Complications; Disease-Free Survival; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Sirolimus; Stents; Thrombosis; Treatment Outcome; Ultrasonography, Interventional

Sirolimus-eluting stents have been developed to prevent restenosis in the treatment of coronary artery disease. We investigated the risk of restenosis with use of sirolimus-eluting stents compared with bare-metal stents to assess possible differences.. We enrolled 352 patients in whom one coronary artery required treatment, with diameter 2.5-3.0 mm and lesion length 15-32 mm. We randomly assigned patients sirolimus-eluting stents (n=175) or bare-metal stents (control, n=177). At 8 months we assessed differences in minimum lumen diameter and binary restenosis within the lesion (restenosis of > or =50% diameter, including 5 mm vessel segments proximal and distal to stented segment). Patients were also followed up for 9 months for major adverse cardiac events. Analysis was by intention to treat.. Stent implantation was successful in 100% of sirolimus-stent patients and 99.4% of controls. The mean diameter of treated coronary arteries was 2.55 mm (SD 0.37) and mean lesion length was 15.0 mm (6.0). Multiple stents were implanted in 170 (48%) patients. At 8 months, minimum lumen diameter was significantly higher with sirolimus-eluting stents than with control stents (2.22 vs 1.33 mm, p<0.0001). The rate of binary restenosis was significantly reduced with sirolimus-eluting stents compared with control stents (5.9 vs 42.3%, p=0.0001). Significantly fewer patients with sirolimus-eluting stents had major adverse cardiac events at 9 months than did controls (8.0 vs 22.6%, p=0.0002), due mainly to a lower need for target-lesion revascularisations (4.0 vs 20.9%, p<0.0001).. Sirolimus-eluting stents are better than bare-metal stents for treatment of single long atherosclerotic lesions in a coronary vessel smaller than 3 mm in diameter.

Topics: Angioplasty, Balloon; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Female; Humans; Immunosuppressive Agents; Male; Metals; Middle Aged; Sirolimus; Stents; Treatment Outcome

Sirolimus-eluting stents (SES) have recently been proven to reduce restenosis and reintervention compared with bare stents. Safety and effectiveness of SES in acute myocardial infarction remain unknown.. Since April 16, 2002, a policy of routine SES implantation has been instituted in our hospital, with no clinical or anatomic restrictions, as part of the RESEARCH (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry. During 6 months of enrollment, 96 patients with ST-elevation acute myocardial infarction underwent percutaneous recanalization and SES implantation; these patients comprise the study population. The incidence of major adverse cardiac events (death, nonfatal myocardial infarction, reintervention) was evaluated. Six-month angiographic follow-up was scheduled per protocol. At baseline, diabetes mellitus was present in 12.5% and multivessel disease in 46.9%. Primary angioplasty was performed in 89 patients (92.7%). Infarct location was anterior in 41 (42.7%) of the cases, and 12 patients (12.5%) had cardiogenic shock. Postprocedural TIMI-3 flow was achieved in 93.3% of the cases. In-hospital mortality was 6.2%. One patient (1.1%) had reinfarction and target lesion reintervention the first day as a result of distal dissection and acute vessel occlusion. During follow-up (mean follow-up of 218+/-75 days), 1 patient died (1.1%), no patient had recurrent myocardial infarction, and there were no additional reinterventions. No early or late stent thromboses were documented. At angiographic follow-up (70%), late loss was -0.04+/-0.25, and no patient presented angiographic restenosis.. In this study, sirolimus-eluting stent implantation for patients with ST-elevation acute myocardial infarction was safe without documented angiographic restenosis at 6 months.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Drug Implants; Electrocardiography; Follow-Up Studies; Humans; Immunosuppressive Agents; Middle Aged; Myocardial Infarction; Sirolimus; Stents; Treatment Outcome

The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent.. In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2+/-5 versus 37+/-28 mm3) and percent of volume obstruction (1+/-3% versus 29+/-20%) at 6 months between the 2 groups was highly significant (P<0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition in the sirolimus group compared with the uncoated stent group (P<0.05), it was not associated with any adverse clinical events at 1 year.. Sirolimus-eluting stents are effective in preventing neointimal hyperplasia without creating edge effect and without affecting the plaque burden behind the struts.

Topics: Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Double-Blind Method; Drug Administration Routes; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Sirolimus; Stents; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional; Vascular Patency

Early results of sirolimus-eluting stent implantation showed a nearly complete abolition of neointimal hyperplasia. The question remains, however, whether the early promising results will still be evident at long-term follow-up. The objective of our study was to evaluate the efficiency of sirolimus-eluting stent implantation for up to 2 years of follow-up.. Fifteen patients with de novo coronary artery disease were treated with 18-mm sirolimus-eluting Bx-Velocity stents (Cordis) loaded with 140 microg sirolimus/cm2 metal surface area in a slow release formulation. Quantitative angiography (QCA) and intravascular ultrasound (IVUS) were performed according to standard protocol. Sirolimus-eluting stent implantation was successful in all 15 patients. During the in-hospital course, 1 patient died of cerebral hemorrhage after periprocedural administration of abciximab, and 1 patient underwent repeat stenting after 2 hours because of edge dissection that led to acute occlusion. Through 6 months and up to 2 years of follow-up, no additional events occurred. QCA analysis revealed no significant change in stent minimal lumen diameter or percent diameter stenosis, and 3-dimensional IVUS showed no significant deterioration in lumen volume. In 2 patients, additional stenting was performed because of significant lesion progression remote from the sirolimus-eluting stent.. Sirolimus-eluting stents showed persistent inhibition of neointimal hyperplasia for up to 2 years of follow-up.

Topics: Abciximab; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Implants; Female; Follow-Up Studies; Humans; Hyperplasia; Immunoglobulin Fab Fragments; Immunosuppressive Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Reoperation; Sirolimus; Stents; Time; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, approximately 40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents.. Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into tertiles according to their reference diameter (RD; stratum I, RD <2.36 mm; stratum II, RD 2.36 mm to 2.84 mm; stratum III, RD >2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01+/-0.25 versus 0.80+/-0.43 mm in stratum I, 0.01+/-0.38 versus 0.88+/-0.57 mm in stratum II, and -0.06+/-0.35 versus 0.74+/-0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (Delta -0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, DeltaMLD <-0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (P<0.001) and postprocedural MLD (P= 0.008).. Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Double-Blind Method; Humans; Immunosuppressive Agents; Sirolimus; Stents

The sirolimus-eluting stent (SES) is emerging as a potential solution for the prevention of restenosis. Although the outcome of side branches after stenting with an uncoated metal stent (UMS) has been reported, the fate of side branches after SES implantation is unknown. Furthermore, the absence of spontaneous recanalization of occluded side branches following intracoronary brachytherapy has been previously described and has been related to a delayed healing process. We assessed the procedural and 6-month follow-up angiograms of 238 patients enrolled in the RAVEL study, a double-blind controlled trial of the SES versus the UMS. Any side branch seen on the preprocedure angiogram and subsequently covered by the stent was evaluated. The side branch Thrombolysis In Myocardial Infarction (TIMI) flow grade was assessed at baseline and at follow-up by 2 observers. One hundred twenty-eight patients with > or =1 side branches were identified (63 patients in the SES group with 118 side branches, 65 patients in the UMS group with 124 side branches). Side branch occlusion occurred after stenting in 12 branches (10%) in the SES group and in 9 branches (7%) in the UMS group (p = NS). Of these occluded branches, spontaneous recanalization was observed in 11 branches (92%) in the SES group and in 6 branches (67%) in the UMS group at follow-up angiography (p = NS). Thus, the fate of side branches after SES implantation is favorable and at least as good as after UMS implantation.

Topics: Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Double-Blind Method; Follow-Up Studies; Humans; Immunosuppressive Agents; Predictive Value of Tests; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization. Because sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle cells, we compared a sirolimus-eluting stent with a standard uncoated stent in patients with angina pectoris.. We performed a randomized, double-blind trial to compare the two types of stents for revascularization of single, primary lesions in native coronary arteries. The trial included 238 patients at 19 medical centers. The primary end point was in-stent late luminal loss (the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months). Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis (luminal narrowing of 50 percent or more). We also analyzed a composite clinical end point consisting of death, myocardial infarction, and percutaneous or surgical revascularization at 1, 6, and 12 months.. At six months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the sirolimus-stent group, as compared with 26.6 percent of those in the standard-stent group, had restenosis of 50 percent or more of the luminal diameter (P<0.001). There were no episodes of stent thrombosis. During a follow-up period of up to one year, the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001). The difference was due entirely to a higher rate of revascularization of the target vessel in the standard-stent group.. As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events.

Topics: Coronary Disease; Coronary Restenosis; Coronary Vessels; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Sirolimus; Stents; Tunica Intima; Ultrasonography, Interventional

Restenosis remains an important limitation of interventional cardiology. Therefore, we aimed to determine the safety and efficacy of sirolimus (a cell-cycle inhibitor)-coated BX Velocity stents.. Thirty patients with angina pectoris were electively treated with 2 different formulations of sirolimus-coated stents (slow release [SR], n=15, and fast release [FR], n=15). All stents were successfully delivered, and patients were discharged without clinical complications. Independent core laboratories analyzed angiographic and 3D volumetric intravascular ultrasound data (immediately after procedure and at 4-month follow-up). Eight-month clinical follow-up was obtained for all patients. There was minimal neointimal hyperplasia in both groups (11.0+/-3.0% in the SR group and 10.4+/-3.0% in the FR group, P:=NS) by ultrasound and quantitative coronary angiography (in-stent late loss, 0.09+/-0.3 mm [SR] and -0.02+/-0.3 mm [FR]; in-lesion late loss, 0.16+/-0.3 mm [SR] and -0.1+/-0.3 mm [FR]). No in-stent or edge restenosis (diameter stenosis >or=50%) was observed. No major clinical events (stent thrombosis, repeat revascularization, myocardial infarction, or death) had occurred by 8 months.. The implantation of sirolimus-coated BX Velocity stents is feasible and safe and elicits minimal neointimal proliferation. Additional placebo-controlled trials are required to confirm these promising results.

Topics: Aged; Arteries; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Delayed-Action Preparations; Feasibility Studies; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pilot Projects; Sirolimus; Stents; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

Few studies compared paclitaxel-coated balloon (PCB) versus sirolimus-coated balloon (SCB) in the treatment of drug-eluting stent (DES) instent restenosis (ISR).. Between November 5, 2009, and October 14, 2020, in our center 212 patients with first DES-ISR were treated with PCB (Restore. Procedural success occurred in all cases. Fully optimal predilation (that is, balloon-to-stent ratio >0.91, time of DCB inflation >60 sec, and residual percent diameter stenosis after lesion preparation <20%) was observed more often in the SCB group (126 [68%] patients versus 106 [57%] patients; P=0.042). One-year TLF occurred in 29 (15.5%) patients in the SCB group and in 32 (17%) patients in the PCB group (OR=1.12 [0.65-1.95]; P=0.78). By logistic Cox regression analysis fully optimal predilation (OR=0.06; 95% CI: 0.01-0.21; P<0.001) but not DCB type (OR=0.74; 95% CI: 0.41-1.31; P=0.29) was independent predictor of 1-year TLF.. The current study suggests that 1-year TLF is not statistically and clinically different in patients with DES ISR treated with a PCB and a SCB.

Topics: Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus; Time Factors; Treatment Outcome

Topics: Atherectomy, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Treatment Outcome

Drug-eluting stents (DES) are mostly used in percutaneous coronary intervention, which is the main treatment for coronary artery occlusion. This procedure aims to restore the natural lumen, while minimizing the risk of restenosis. However, stent insertion increases the risk for infections, due to contamination of the device or insertion hub with normal skin flora. While coronary stent infection is a rare complication, it can be fatal. Currently, there is little information on biofilm formation on everolimus-eluting stents. Although everolimus is not designed as an antimicrobial agent, its antimicrobial activity should be investigated. In this study, biofilm formation on everolimus-eluting and bare metal stents (BMS) is characterized through biochemical and electrochemical methods. DES and BMS are inoculated with Pseudomonas aeruginosa and Staphylococcus epidermidis, both independently and in co-culture. Biofilms formed on DES were 49.6 %, 12.9 % and 47.5 % higher than on BMS for P. aeruginosa, S. epidermidis and their co-culture, respectively. Further, the charge output for DES was 18.9 % and 59.7 % higher than BMS for P. aeruginosa and its co-culture with S. epidermidis, respectively. This observation is most likely due to higher surface roughness of DES, which favors biofilm formation. This work shows that bioelectrochemical methods can be used for rapid detection of biofilms on drug-eluting and bare metal stents, which may find application in quality assessment of stents and in characterization of stents removed after polymicrobial infections.

Topics: Biofilms; Cardiovascular Agents; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Metals; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

Drug eluting magnesium (Mg) bioresorbable scaffolds represent a novel paradigm in percutaneous coronary intervention because Mg-based alloys are biocompatible, have adequate mechanical properties and can be resorbed without adverse events. Importantly, Mg is fundamental in many biological processes, mitigates the inflammatory response and is beneficial for the endothelium. Sirolimus is widely used as an antiproliferative agent in drug eluting stents to inhibit the proliferation of smooth muscle cells, thus reducing the occurrence of stent restenosis. Little is known about the potential interplay between sirolimus and Mg in cultured human coronary artery endothelial cells (hCAEC). Therefore, the cells were treated with sirolimus in the presence of different concentrations of extracellular Mg. Cell viability, migration, barrier function, adhesivity and nitric oxide synthesis were assessed. Sirolimus impairs the viability of subconfluent, but not of confluent cells independently from the concentration of Mg in the culture medium. In confluent cells, sirolimus inhibits migration, while it cooperates with Mg in exerting an anti-inflammatory action that might have a role in preventing restenosis and thrombosis.

Topics: Coronary Restenosis; Endothelial Cells; Endothelium; Humans; Magnesium; Sirolimus; Stents; Treatment Outcome

Topics: Carotid Arteries; Constriction, Pathologic; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Male; Sirolimus; Stents; Treatment Outcome

A decade ago, the iopromide-paclitaxel coated balloon (iPCB) was added to the cardiologist's toolbox to initially treat in-stent restenosis followed by the treatment of de novo coronary lesions. In the meantime, DES technologies have been substantially improved to address in-stent restenosis and thrombosis, and shortened anti-platelet therapy. Recently, sirolimus-coated balloon catheters (SCB) have emerged to provide an alternative drug to combat restenosis.. The objective of this study is to determine the safety and efficacy of a novel crystalline sirolimus-coated balloon (cSCB) technology in an unselective, international, large-scale patient population. Percutaneous coronary interventions of native stenosis, in-stent stenosis, and chronic total occlusions with the SCB in patients with stable coronary artery disease or acute coronary syndrome were included. The primary outcome variable is the target lesion failure (TLF) rate at 12 months, defined as the composite rate of target vessel myocardial infarction (TV-MI), cardiac death or ischemia-driven target lesion revascularization (TLR). The secondary outcome variables include TLF at 24 months, ischemia driven TLR at 12 and 24 months and all-cause death, cardiac death at 12 and 24 months.. Since there is a wealth of patient-based all-comers data for iPCB available for this study, a propensity-score matched analysis is planned to compare cSCB and iPCB for the treatment of de novo and different types of ISR. In addition, pre-specified analyses in challenging lesion subsets such as chronic total occlusions will provide evidence whether the two balloon coating technologies differ in their clinical benefit for the patient.. ClinicalTrials.gov Identifier: NCT04470934.

Topics: Angioplasty; Cardiovascular Agents; Clinical Trials as Topic; Constriction, Pathologic; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus; Treatment Outcome

The safety and efficacy of drug-eluting balloon on the treatment of intracranial atherosclerotic stenosis (ICAS) remain unclear. Here, we present our observation in a cohort study on the safety and efficacy of rapamycin-eluting balloon for patients with ICAS.. A total of 80 ICAS patients with stenosis degree of 70-99% were included. All patients were treated with rapamycin-eluting balloon and were followed up for 12 months after operation.. All patients were successfully treated, where the mean stenosis severity reduced from 85.1 ± 7.6 to 6 ± 4.9%. 8 patients experienced immediate post-operational complications. Two patients passed away during the first month of the follow-up period. Recurrent ischemic syndrome and angiographic restenosis only appeared 7 days after operation. During later follow-up period, none of the patients had clinical angiographic restenosis or needed target vessel revascularization.. Our data suggest that intracranial stenting with rapamycin-eluting balloon seems to be safe and effective, although more clinical data are needed to support this notion.

Topics: Cohort Studies; Constriction, Pathologic; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Intracranial Arteriosclerosis; Sirolimus; Stents; Treatment Outcome

Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications.. This study sought to understand the role of a novel SCB for the treatment of coronary artery disease.. EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee.. A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881).. EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Humans; Middle Aged; Myocardial Infarction; Registries; Sirolimus; Treatment Outcome

Topics: Coronary Aneurysm; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Myocardial Infarction; Sirolimus; Stents; Treatment Outcome

Persistence of the pathology of in-stent restenosis even with the advent of drug-eluting stents warrants the development of highly resolved in silico models. These computational models assist in gaining insights into the transient biochemical and cellular mechanisms involved and thereby optimize the stent implantation parameters. Within this work, an already established fully-coupled Lagrangian finite element framework for modeling the restenotic growth is enhanced with the incorporation of endothelium-mediated effects and pharmacological influences of rapamycin-based drugs embedded in the polymeric layers of the current generation drug-eluting stents. The continuum mechanical description of growth is further justified in the context of thermodynamic consistency. Qualitative inferences are drawn from the model developed herein regarding the efficacy of the level of drug embedment within the struts as well as the release profiles adopted. The framework is then intended to serve as a tool for clinicians to tune the interventional procedures patient-specifically.

Topics: Computer Simulation; Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus; Stents

To assess the value of sirolimus-eluting magnesium bioresorbable scaffolds (MgS) in the treatment of patients with in-stent restenosis (ISR). The better option for the treatment of patients with ISR remains unsettled. Bioresorbable vascular scaffolds represent an interesting strategy in this setting to avoid another permanent metal layer. The novel MgS is an attractive option to treat these challenging patients.. We present the results of the first prospective series of consecutive patients with ISR treated with MgS under optical coherence tomography (OCT) guidance.. A total of 14 patients (15 lesions) were prospectively included. The mean age was 67 ± 9 years and six patients (40%) presented with an acute coronary syndrome. In 10 patients (67%), underlying neoatherosclerosis was disclosed by OCT. An excellent MgS expansion was obtained in all but two patients who showed persistent suboptimal expansion in heavily calcified vessels. Minor residual malapposition ( n = 5) and angiographically silent minor edge dissections ( n = 8) were readily recognized by OCT. After a median clinical follow-up of 30 (range, 20-54) months, no patient required repeated revascularization, suffered a myocardial infarction or device thrombosis.. These preliminary results suggest a potential role for the MgS in selected patients presenting with ISR.

Topics: Absorbable Implants; Aged; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Magnesium; Middle Aged; Prospective Studies; Prosthesis Design; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Humans; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Clinical evidence demonstrating the impact of statins for preventing late target lesion revascularization (TLR) after newer-generation drug-eluting stent implantation and differences in the effect of statins on late TLR according to pre-interventional vessel remodeling and vessel size is limited. We retrospectively evaluated 1193 de novo lesions in 720 patients who underwent everolimus-eluting stent implantation using intravascular ultrasound from January 2010 to December 2012. The primary endpoint was late TLR. Lesions were divided into the statin group (n = 825) and non-statin group (n = 368). The incidence of late TLR was significantly lower in the statin than non-statin group (1.7% vs. 5.2%, respectively; p = 0.001), and within the statin group, it was significantly lower in the follow-up low-density lipoprotein cholesterol (LDL-C) < 100 than ≥ 100 mg/dL level subgroup (1.0% vs. 3.6%, respectively; p = 0.006). Furthermore, in positive remodeling lesions and non-small vessel size lesions, the incidence of late TLR was significantly lower in the statin than non-statin group (1.6% vs. 8.5% and 1.3% vs. 5.3%, respectively; p = 0.001 and p = 0.004). Lowering the LDL-C level using statins was more effective for preventing late TLR after everolimus-eluting stent implantation. Evaluating pre-interventional vessel remodeling patterns and vessel size might be helpful to stratify lesions at high risk of late TLR.

Topics: Cholesterol, LDL; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Risk Factors; Sirolimus; Treatment Outcome

Paclitaxel-coated balloons (PCBs) are a preferred treatment option for coronary in-stent restenosis. To date, data from randomized trials of alternative drug coatings are lacking. The aim of the randomized Malaysian and German-Swiss randomized trials was to investigate a novel sirolimus-coated balloon (SCB) compared with a PCB in in-stent restenosis.. One hundred one patients with drug-eluting stent in-stent restenosis were enrolled in 2 identical randomized trials comparing the novel SCB (SeQuent SCB, 4 μg/mm²) with the clinically proven PCB (SeQuent Please, 3 μg/mm²). Primary end point was angiographic late lumen loss at 6 months. Secondary end points included procedural success, major adverse cardiac events, and individual clinical end points such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis.. Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.25±0.57 mm in the PCB group versus 0.26±0.60 mm in the SCB group. Mean difference between SCB and PCB was 0.01 (95% CI, -0.23 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. Clinical events up to 12 months did not differ between the groups.. This first-in man comparison of a novel SCB with a crystalline coating showed similar angiographic and clinical outcomes in the treatment of coronary drug-eluting stent in-stent restenosis compared with PCB.. URL: https://www.. gov; Unique identifier: NCT02996318, NCT03242096.

Topics: Angioplasty, Balloon, Coronary; Constriction, Pathologic; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Polychlorinated Biphenyls; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Percutaneous coronary intervention (PCI) is an effective treatment for acute myocardial infarction, but the postoperative in-stent re-stenosis (ISR) remains a major risk factor that affects the prognosis of PCI. Clinically, drug-eluting stents (DES) are widely applied to prevent and treat ISR. However, only a few stent coating drugs are currently available for clinical use, including paclitaxel and rapamycin (sirolimus) and their derivatives. These stent-coated drugs have led to a decrease in restenosis rates, but the major adverse outcomes, such as delayed endothelial healing and increased in-stent thrombosis, seriously reduce their therapeutic effects.. Herein, we explored the potential efficacy of Euonymine (Euo), an alkaloid extracted from Tripterygium Hypoglaucum (Levl) Hutch (THH, Lei gong Teng), for the prevention against ISR after PCI.. Our study depicts the potential efficacy of Euo in treating ISR and explores its mechanism with in vitro and in vivo models.. Primary vascular smooth muscle cells (VSMCs) from the rabbit thoracic aorta were cultured, and the proliferation and migration of VSMCs were monitored. Apoptosis was measured by Transmission Electron Microscopy and TUNEL staining assay. Protein and gene levels were measured to explore the underlying molecular mechanisms. In vivo models of porcine coronary implantation and rabbit carotid balloon injury are used to validate the efficacy of Euo in inhibiting ISR after PCI.. With an ox-LDL-injured cell model, we showed that Euo suppressed the proliferation and migration of the rabbit thoracic aorta primary VSMCs, while inducing their apoptosis. We next established a rabbit carotid balloon injury model in which the phosphorylation levels of PI3K and AKT1 (Ser473) as well as mTOR activity were significantly elevated compared to the sham-operated control. These activities were significantly attenuated by the Euo intervention. Additionally, the balloon angioplasty significantly increased the expression of Bcl-2, while decreased the expression of Bax and caspase-3. Euo intervention significantly increased the ratio of Bax/Bcl-2 and the level of caspase-3. Taken together, Euo may enhance the VSMCs contractile phenotype by modulating the PTEN/AKT/mTOR signaling pathway. Furthermore, with two in vivo models, the porcine coronary artery implantation model, and the rabbit carotid balloon injury model, we demonstrated that Euo-eluting stents indeed inhibited ISR after PCI.. For the first time, this study delineates the potential efficacy of Euo, derived from Tripterygium Hypoglaucum (Levl) Hutch, in ameliorating ISR after PCI with two in vivo models. The phytochemical targets PTEN/AKT/mTOR signaling pathway to increase the contractile phenotype of VSMCs and exerts anti-proliferative, anti-migratory as well as pro-apoptotic effects, thereby inhibiting the ISR.

Topics: Animals; bcl-2-Associated X Protein; Caspase 3; Constriction, Pathologic; Coronary Angiography; Coronary Restenosis; Muscle, Smooth, Vascular; Paclitaxel; Percutaneous Coronary Intervention; Phenotype; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rabbits; Risk Factors; Signal Transduction; Sirolimus; Swine; TOR Serine-Threonine Kinases; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; C-Reactive Protein; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Sirolimus; Treatment Outcome; Troponin I

BACKGROUND Use of drug-coated balloons (DCB) is an important research topic. Many companies are quickly developing new, cutting-edge technologies and means to deliver drugs. Moreover, interest is growing in use of sirolimus-coated balloons, a promising technology in the "leaving nothing behind" era. This, in combination with interest in lesion preparation and intravascular imaging, creates a promising future for DCB for years to come. CASE REPORT A 72-year-old patient presented with NSTEMI. Coronary angiography showed a subtotal stenosis of the right coronary artery (RCA). PCI was performed on the native RCA and, given the patient's failure to adhere to the drug regimen, he was treated with a metal-free PCI strategy. After using a novel lesion preparation technique with cutting balloon and high-pressure non-compliant balloon, a novel Sirolimus DCB was used. Final angiography and OCT run showed good luminal gain despite diffuse dissections. To assess vascular healing, we performed coronary angiography 5 weeks later, which demonstrated an excellent result, with absence of residual dissection and further luminal gain compared to the index procedure. CONCLUSIONS The use of a novel lesion preparation technique (cutting balloon and high-pressure highly non-compliant balloon) in combination with guidance by intravascular imaging and the use of a new sirolimus-coated balloon may attract attention in the interventional cardiology community and stimulate discussion on lesion preparation and use of drug-coated balloons.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Humans; Male; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome

To investigate the effectiveness of metformin and atorvastatin in preventing in-stent restenosis (ISR) on coronary patients with type 2 diabetes mellitus with percutaneous coronary intervention within 8 to 12 months after rapamycin-eluting stent implantation. A total of 1278 consecutive patients implanted with rapamycin-eluting stent from January 2012 to December 2019, who underwent coronary computed tomography or coronary angiography within 8 to 12 months. The patients were categorized into atorvastatin 20 mg, or atorvastatin 20 mg + metformin 1.5/d, or atorvastatin 40 mg + metformin 1.5/d groups. The clinical characteristics of the 3 groups were compared. The correlation between variables and ISR was analyzed. A total of 701 patients participated in the study. The ratio of ISR/nonstenosis (P = .039) and fasting blood sugar (P = .001) differed significantly in the 3 groups. Logistic regression showed that d, L, different therapeutic agents, and dosage groups were independent risk factors of ISR. The longer L and smaller d may increase ISR incidence with 8 to 12 months after percutaneous coronary intervention. Both metformin and atorvastatin are beneficial in reducing stent restenosis by a dose-dependent manner. An increasing dose of atorvastatin and a combination of metformin decreases the incidence of ISR in patients.

Topics: Atorvastatin; Blood Glucose; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Humans; Metformin; Percutaneous Coronary Intervention; Risk Factors; Sirolimus; Stents; Treatment Outcome

Drug-eluting stents (DES) significantly improved angiographic and clinical outcomes compared with bare-metal stents in patients with diabetes. The clinical effects of BioMime sirolimus-eluting stent (SES) in patients with diabetes have not been evaluated. Therefore, we compared the efficacy of BioMime DES in coronary artery disease (CAD) patients with versus without diabetes.. This prospective analytical study compared angiographic in-segment late loss and clinical effectiveness of BioMime SES stents in treating patients with (patients: 77 and lesions: 83) versus without (patients: 154 and lesions: 162) diabetes. The purpose of this study was the comparison of angiographic in-segment late loss at 12 months. Major adverse cardiac events (MACEs) were also monitored as secondary outcomes 24 months after the index procedure.. Of 231 patients enrolled in the study, the mean age was 63.3 years and 153 patients were male. Angiographic follow-up rate was 84.8% (patients: 196) and intravascular ultrasound (IVUS) follow-up rate was 67.9% (patients: 157) at 12 months. Diabetic patients were comparable to nondiabetic patients for 12-month in-segment late loss (0.01 ± 0.31 mm for the nondiabetes group versus 0.04 ± 0.11 mm for the diabetes group; P = 0.158; P < 0.05). At 24 months, MACEs, including death, myocardial infarction and ischemic-driven target lesion revascularization were not statistically different between the two treatment groups.. BioMime SES stents in treating patients with diabetes were comparable in reducing angiographic restenosis at 12 months and MACEs at 24 months compared to nondiabetic patients with CAD.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Prospective Studies; Sirolimus; Stents; Treatment Outcome

Limus-eluting stents have become the mainstay for percutaneous coronary intervention (PCI). However, even with the latest generation drug-eluting stent, in-stent restenosis and very late stent thrombosis remain a concern. The Selution SLR™ drug-coated balloon (DCB) is a novel sirolimus-coated balloon that provides a controlled release of the antiproliferative drug. Herein we evaluated its performance in a real-world patient cohort with complex coronary artery lesions.. Patients undergoing PCI using the Selution SLR™ DCB were analyzed from the prospective SIROOP registry. We evaluated procedural success and clinical outcomes, including major adverse cardiovascular event (MACE), cardiac death, target vessel myocardial infarction and target lesion revascularization.. From September 2020 to April 2021, we enrolled 78 patients (87 lesions) treated using a "DCB only" strategy. The mean age was 66.7 ± 10.4 years and 28 (36%) presented with an acute coronary syndrome. Almost all lesions were type B2/C 86 (99%) and 49 (63%) had moderate to severe calcifications. Procedural success was 100%. After a median follow-up of 11.2 months (interquartile range: 10.0-12.6), MACE occurred in 5 (6.8%) patients. No acute vessel closure was observed.. In complex coronary lesions, a "DCB only" strategy using the Selution SLR™ DCB is not just safe and feasible, but also seems to be associated with a low rate of MACE at 1-year follow-up. Our promising results warrant further evaluation in a dedicated comparative trial.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Metals; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Treatment Outcome

Drug-eluting stents (DES) coated with rapamycin or paclitaxel as antiproliferative substances significantly reduced the incidence of clinical restenosis and had fewer side effects after percutaneous coronary intervention. However, DES coated with rapamycin or paclitaxel still cause restenosis due to abnormal tissue growth which remained a therapeutic problem, particularly in certain subgroups, possibly due to drug concentrations. This study examined the impact of different concentrations of rapamycin and paclitaxel on cytokine, cell viability and proliferation in human aortic smooth muscle cells (HASMC)-derived foam cells.. The foam cell model was established in vitro by incubating HASMC with 20 µg/mL oxidized low-density lipoprotein (ox-LDL) for 48 hours. Subsequently, foam cells were treated with different concentrations (0.01 µg/mL, 0.1 µg/mL, 0.5 µg/mL, 1 µg/mL, 5 µg/mL and 10 µg/mL) of rapamycin or paclitaxel for 48 hours, to measure cytokine, cell viability and proliferation by ELISA and MTT, respectively. Finally, viability and proliferation were measured by MTT after the foam cells were treated with 1 µg/mL rapamycin or paclitaxel combined with cytokine antibody for 48 hours.. After incubation of HASMC with ox-LDL, the ratios of cholesterol ester and total cholesterol increased significantly (55.29%) (P<0.01). Lipid staining with Oil Red O showed many lipid vacuoles and red dye particles in the cells. Meanwhile, cell viability and proliferation significantly increased compared with the control. This indicated that HASMC had been transformed into foam cells (P<0.01) while rapamycin or paclitaxel concentrations ≥0.1 µg/mL can significantly decrease the foam cell proliferation (P<0.05 or P<0.01), and 1 µg/mL of rapamycin or paclitaxel appeared the most effective concentration. As for cytokines, rapamycin or paclitaxel concentrations ≥1 ug/mL could significantly increase the level of inflammatory cytokines IL-6 (P<0.05 or P<0.01), which was enhanced with the increase of drug concentration. However, rapamycin or paclitaxel concentrations ≥1 µg/mL could significantly reduce the levels of anti-inflammatory cytokines IL-35 and transforming growth factor beta (TGF-β) (P<0.05 or P<0.01), which decreased with the increase of drug concentration. In addition, rapamycin or paclitaxel combined with anti-IL-1β, anti-IL-6, anti- TNF-α or anti-IL-35 had no significant effect on foam cell proliferation compared to the drug alone. However, rapamycin or paclitaxel combined with anti-IL-10 or anti-TGF-β can significantly enhance foam cell proliferation (P<0.01). In addition, there was no difference in the effects of the same concentrations of rapamycin and paclitaxel on foam cells.. Although rapamycin or paclitaxel can reduce foam cell proliferation, too high or too low concentrations could decrease effectiveness. In particular, a high dose can induce foam cells to increase inflammatory cytokines secretion, reduce anti-inflammatory cytokines secretion, and thus affect the inhibiting proliferation. For rapamycin- and paclitaxel-eluting stents, this conclusion may explain the clinical observation of in-stent restenosis after percutaneous coronary intervention. DES coated with an appropriate concentration of rapamycin or paclitaxel may, at least to some extent, contribute significantly to reducing incidence of late in-stent restenosis.

Topics: Cell Proliferation; Coronary Restenosis; Cytokines; Foam Cells; Humans; Myocytes, Smooth Muscle; Paclitaxel; Sirolimus; Stents

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus

Cardiovascular disease (CVD) with significant involvement of coronary artery disease (CAD) remains a major cause of death and disability among the diabetic population. Although percutaneous coronary intervention (PCI) continues to evolve, type 2 diabetes mellitus (T2DM) is a well-established marker of poor clinical prognosis after PCI, which is mainly attributed to the rapid progression of atherosclerosis requiring recurrent revascularizations. Hence, the use of bioresorbable materials could provide some solution to this problem.. There were no significant differences between the diabetic and nondiabetic populations in primary endpoints or main secondary endpoints (TLF, scaffold restenosis, death from any reason, and other cardiovascular events) either in the Ultimaster or Magmaris group. At a 1-year-follow-up, the primary endpoint in the DM t.2 population was recorded in 2.7% Ultimaster vs. 5.1% Magmaris, respectively. At the same time, the TLF occurred in the diabetic group in 4.1% Magmaris and 3.3% in the Ultimaster arm, respectively.. Both, Ultimaster and Magmaris revealed relative safety and efficiency at a one-year follow-up in the diabetic population in ACS settings. The observed rates of TLF were low, which combined with a lack of in-stent thrombosis suggests that both investigated devices might be an interesting therapeutic option for diabetics with ACS. Nevertheless, further large randomized clinical trials are needed to confirm fully our results.

Topics: Absorbable Implants; Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Restenosis; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Magnesium; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Polymers; Prosthesis Design; Recurrence; Retrospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Coronary artery disease (CAD) is chiefly characterized by atherosclerosis and plaque formation in coronary arteries. The aim of this study was to evaluate the correlation of coronary anatomy as a predictor of restenosis and stent thrombosis in coronary artery disease (CAD) patients 5 years after percutaneous coronary intervention (PCI).. In this prospective study, 1070 patients with stent restenosis or stent thrombosis over past 5 years were enrolled. Coronary angiography was performed to evaluate coronary restenosis and stent thrombosis 5 years after PCI. Stent restenosis was defined as >50% angiographic in-stent lumen reduction. Stent thrombosis was defined as sudden complete occlusion of stent presenting with acute myocardial infarction in that territory. Demographic data, clinical features and anatomic factors were prospectively reviewed. Baseline, procedural, and post-procedural characteristics of patients were recorded for analysis.. Among demographic characteristics, cardiovascular risk factors (hypertension and diabetes mellitus) and anatomic factors were predictive risk factors for restenosis/thrombosis, p=0.001. The most common site for stent restenosis was proximal to the mid part of the LAD artery, followed by RCA and LCX. A greater diameter of LCX, a greater angle of LM-LAD than LM-LCX and left dominancy increase the incidence of LAD stent restenosis/thrombosis. In this study, the least common restenosis/thrombosis rate in relation to the total number of PCI was in the Ramus intermedius artery.. The outcomes of the study indicated that anatomic factors can predict increased risk of restenosis among CAD patients who underwent PCI.

Topics: Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Humans; Incidence; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Stents; Treatment Outcome

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus

This study aimed to evaluate the pharmacokinetic profile and tissue effects of everolimus delivered into arterial wall using biodegradable nanospheres.. Delivery of everolimus into the arterial wall is challenging due to its low-lipophilic profile.. A pharmacokinetic study included 28 porcine coronary arterial segments initially injured with balloon angioplasty followed by the local delivery of everolimus encapsulated in nanospheres (EEN) via injection through a microporous delivery catheter. The animals were sacrificed at 1 hour, 1,7,28, and 90-day follow-up. In the tissue effects study 16 coronary bare metal stent (BMS) were implanted following EEN delivery, 15 BMS following nanospheres delivery without the drug (reference group) and 16 implanted BMS served as a control. Angiographic and histology follow-up was scheduled at 28 and 90-day.. The study showed high-everolimus concentrations in arterial tissue early after nanoparticles delivery followed by its gradual decrease to 1.15 ± 0.40 ng/mg at 90 days. Histology analysis showed favorable biocompatibility and healing profile with comparable area stenosis between groups at both time-points.. The present study demonstrates for the first time the safety, biocompatibility, and long-term retention of everolimus in arterial tissue after single local delivery of biodegradable nanospheres.

Topics: Animals; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Nanospheres; Prosthesis Design; Sirolimus; Stents; Swine; Treatment Outcome

Recent improvements in coronary stent design have focussed on thinner struts, different alloys and architecture, more biocompatible polymers, and shorter drug absorption times. This study evaluates safety and efficacy of a newer generation thin-strut cobalt chromium sirolimus-eluting coronary stent (SES, Ultimaster) in comparison with a second-generation thicker strut stainless steel biolimus-eluting stent (BES, Nobori) in percutaneous coronary intervention (PCI) practice.. A propensity score analysis was performed to adjust for differences in baseline characteristics of 8137 SES patients and 2738 BES patients of two PCI registries (e-Ultimaster and NOBORI 2). An independent clinical event committee adjudicated all endpoint-related adverse events.. The use of SES, as compared with BES was associated with a significantly lower rate of myocardial infarction (MI) (1.2% vs 2.2%; P = 0.0006) and target vessel-related MI (1.1% vs 1.8%; P = 0.002) at 1 year. One-year composite endpoints of all predefined endpoints were lower in patients undergoing SES implantation (target lesion failure: 3.2% vs 4.1%; P = 0.03, target vessel failure: 3.7% vs 5.0%; P = 0.003, patient-oriented composite endpoint 5.7% vs 6.8%; P = 0.03). No significant differences between SES and BES were observed in all-cause death (2.0% vs 1.6%; P = 0.19), cardiac death (1.2% vs 1.2%; P = 0.76) or stent thrombosis (0.6% vs 0.8%; P = 0.43).. These findings suggest an improved clinical safety and efficacy of a newer generation thin-strut SES as compared with a second-generation thicker strut BES.

Topics: Aged; Biocompatible Materials; Chromium Alloys; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Equipment Failure Analysis; Female; Humans; Immunosuppressive Agents; Male; Percutaneous Coronary Intervention; Postoperative Complications; Prosthesis Design; Registries; Sirolimus; Survival Analysis

Interventional therapies such as drug-eluting stents (DES) and drug-coated balloons (DCB) have significantly improved the clinical outcomes of patients with coronary occlusions in recent years. Despite this marked improvement, ischemic cardiovascular disease remains the most common cause of death worldwide. To address this, research efforts are focused on improving the safety and efficacy of the next generation of these devices. However, current experimental methods are unable to account for the influence of atherosclerotic lesions on drug uptake and retention. Therefore, in this study, we used an integrated approach utilizing both in vitro and in silico methods to assess the performance of DCB therapy. This approach was validated against existing in vivo results before being used to numerically estimate the effect of the atheroma. A bolus release of sirolimus was observed with our coating matrix. This, coupled with the rapid saturation of specific and non-specific binding sites observed in our study, indicated that increasing the therapeutic dose coated onto the balloons might not necessarily result in greater uptake and/or retention. Additionally, our findings alluded to an optimal exposure time, dependent on the coating matrix, for the DCBs to be expanded against the vessel. Moreover, our findings suggest that a biphasic drug release profile might be beneficial for establishing and maintaining the saturation of bindings sites within severely occluded vessels. Ultimately, we have demonstrated that computational methods may be capable of assessing the efficacy of DCB therapy as well as predict the influence of atherosclerotic lesions on said efficacy.

Topics: Angioplasty, Balloon, Coronary; Atherosclerosis; Cardiovascular Agents; Computer Simulation; Coronary Occlusion; Coronary Restenosis; Coronary Vessels; Dose-Response Relationship, Drug; Drug Liberation; Drug-Eluting Stents; Humans; Models, Cardiovascular; Sirolimus; Treatment Outcome

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus

Localized drug delivery with sustained elution characteristics from nanocarrier coated stents represents a viable therapeutic approach to circumvent concerns related to coronary stent therapy. We fabricated a Sirolimus (SRL) and Bivalirudin (BIV) releasing nanoparticles (NPs) coated stent for concurrent mitigation of vascular restenosis and acute stent thrombosis. SRL NPs were prepared by nanoprecipitation method whereas the BIV vesicles were generated using hydrophobic ion pair approach followed by micellization phenomenon. MTT assay and confocal microscopic analysis indicated superior anti-proliferative activity and higher cellular uptake of SRL NPs into human coronary artery smooth muscle cells, respectively. DSC and ATR-FTIR techniques confirmed the formation of complex between BIV and phosphatidylglycerol via some weak physical interactions. More than 2 fold rise in log P value was obtained for DSPG-BIV at 3:1 M ratio compared with native BIV solution. The SAXS analysis indicated formation of oligolamellar vesicles of DSPG-BIV complex which was preferentially entrapped into lipophilic lamellae of vesicles. APTT, PT, and TT tests revealed that the BIV vesicles caused significant prolongation of clotting time compared to native BIV solution. The SEM analysis showed uniform and defect free stent coating. In vitro release study demonstrated that SRL and BIV were eluted in a sustained manner from coated stents.

Topics: Coronary Restenosis; Drug-Eluting Stents; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Scattering, Small Angle; Sirolimus; Stents; Thrombosis; X-Ray Diffraction

Although the drug-eluting stent (DES) has become the standard for percutaneous coronary intervention (PCI)-based revascularization, concerns remain regarding the use of DES, mainly due to its permanent rigid constraint to vessels. A drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be absorbed entirely after its therapeutic period. Magnesium (Mg)-based BRSs have attracted a great deal of attention due to their suitable mechanical properties, innovative chemical features, and well-proven biocompatibility. However, the primary disadvantage of Mg-based BRSs is the rapid degradation rate, resulting in the early loss of structural support long before the recovery of vascular function. Recently, a new type of patented Mg-Nd-Zn-Zr alloy (JDBM) was developed at Shanghai Jiao Tong University to reduce the degradation rate compared to commercial Mg alloys. In the present investigation, a poly(D,L-lactic acid)-coated and rapamycin eluting (PDLLA/RAPA) JDBM BRS was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The degree of smooth muscle cell adhesion to the PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES FIREHAWK were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analyses were performed 180 days after stent implantation to evaluate the technical feasibility, biocompatibility, and degradation characteristics of JDBM BRS in vivo. The results show the ability of a PDLLA/RAPA coated JDBM to inhibit smooth muscle cell adhesion and moderate the drug release rate of JDBM BRS in vitro. In vivo, low local and systemic risks of JDBM BRS were demonstrated in the porcine model, with preserved mechanical integrity after 6 months of implantation. We also showed that this novel BRS was associated with a similar efficacy profile compared with standard DES and high anti-restenosis performance. These findings may confer long term advantages for using this BRS over a traditional DES.

Topics: Alloys; Animals; Aorta, Thoracic; Cell Adhesion; Containment of Biohazards; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Magnesium; Microscopy, Electron, Scanning; Myocytes, Smooth Muscle; Neodymium; Patient Safety; Percutaneous Coronary Intervention; Polyesters; Rats; Sirolimus; Stress, Mechanical; Swine; Tomography, Optical Coherence; X-Ray Microtomography; Zinc; Zirconium

This study aimed to investigate the occurrence and predictive factors of restenosis in coronary heart disease (CHD) patients underwent percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES).. Demographic data, clinical features, and laboratory tests of 398 CHD patients underwent PCI with SES were retrospectively reviewed. Coronary angiography was performed to evaluate coronary stenosis before PCI and in-stent restenosis at 1-year follow-up.. There were 37 (9.3%) patients suffered restenosis, but 361 (90.7%) patients did not develop restenosis at 1-year follow-up. Demographic characteristic (age), cardiovascular risk factors (hypertension and hyperuricemia), biochemical indexes (fasting blood-glucose, total cholesterol, low density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (HsCRP)), cardiac function index (cardiac troponin I), lesion features (multivessel artery lesions, target lesion at left circumflex artery (LCX), two target lesions and length of target lesion), and operation procedure (length of stent) were correlated with higher restenosis risk. Moreover, age, hypertension, diabetes mellitus, LDL-C, HsCRP, and target lesion at LCX were independent predictive factors for raised restenosis risk. Based on these independent predictive factors, we established a restenosis risk prediction model, and receiver-operating characteristic curves displayed that this model exhibited an excellent predictive value for higher restenosis risk (areas under the curve 0.953 (95% CI 0.926-0.981)).. Our findings provide a new insight into the prediction for restenosis in CHD patients underwent PCI with SES.

Topics: Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Retrospective Studies; Risk Factors; Sirolimus; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Immunosuppressive Agents; Sirolimus; Stents; Treatment Outcome

To test the long-term efficacy of a sirolimus-coated balloon (SCB).. Nanoluté was a prospective registry to evaluate the clinical performance of a novel SCB (Concept Medical Research Private Limited, India) for the treatment of de novo coronary lesions and in-stent restenosis (ISR). We here present the 24 months clinical data.. All patients treated with SCB for any type of coronary indication between July 2012 and September 2015 were enrolled at Indian centers and clinically followed up to 24 months. Primary endpoints were major adverse cardiovascular events (MACE) defined as a composite of cardiac death, target lesion revascularization (TLR), and target vessel-myocardial infarction (MI).. A total of 484 SCBs were used in 408 patients to treat 435 lesions. In detail, the SCB was used for 183 patients with ISR, 185 with de novo small vessel disease, and 40 with de novo large vessel disease. Mean balloon length and diameter (average ± SD) were 22.3 ± 7.1 mm and 2.7 ± 0.40 mm, respectively. All patients with 24 months follow-up were included. Overall MACE rate was 4.2% (n = 17) with three cardiac deaths (0.7%), 13 TLR (3.2%), and one MI (0.2%).. The Nanoluté prospective registry is the first long-term clinical evidence of the safety and feasibility of this type of SCB, both in patients with ISR or de novo lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Equipment Design; Female; Humans; India; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Heparin; Neointima; Rats; Sirolimus; Stents; Swine

There is a scarcity of comparative studies between Endeavor Resolute®-zotarolimus-eluting stent (R-ZES) and Resolute Integrity®-ZES (I-ZES) during long-term follow-up periods. Although the stent alloy and the polymer of these two ZESs are similar, the platform and the design of these two stents are different. This study was conducted to compare the efficacy and safety of these two different ZESs in the all-comer Korean patients who underwent percutaneous coronary intervention (PCI) during a 3-year follow-up period.. This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. In this single-center, retrospective, and all-comer patients' cohort study, a total of 889 patients who underwent PCI with R-ZES (n=394) or I-ZES (n=495) were enrolled. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, nonfatal myocardial infarction (MI), any repeat revascularization including target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR, and the secondary endpoint was stent thrombosis (ST) at 3 years.. To adjust for any potential confounders, the propensity score-adjusted multivariable analysis was performed using the logistic regression model (C-statistics=0.689). The cumulative incidence rates of MACEs [adjusted hazard ratio (aHR), 1.341; 95% confidence interval (CI), 0.615-2.922; p=0.461], all-cause death, nonfatal MI, any repeat revascularization, and ST (aHR, 2.090; 95% CI, 0.163-26.77; p=0.571) were similar between the two groups during the 3-year follow-up period.. R-ZES and I-ZES demonstrated comparable efficacy and safety after PCI during a 3-year follow-up period. However, these results can perhaps be more precisely defined by other large and long-term follow-up studies in the future. (Anatol J Cardiol 2020; 23: 268-76).

Topics: Asian People; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Republic of Korea; Retrospective Studies; Risk Factors; Sirolimus

RENASCENT is a prospective, multi-center first-in-human clinical study to evaluate the clinical performance of the novel sirolimus-eluting 150-μm strut thickness FORTITUDE® BRS for percutaneous coronary intervention of single de novo coronary lesions.. FORTITUDE® BRS was tested in a prospective study in Italy and Colombia. Study objectives were in-scaffold angiographic late lumen loss (LLL) measured by quantitative coronary angiography and target vessel failure (TVF) defined as the composite rate of cardiac death, target vessel myocardial infarction or ischemia driven target lesion revascularization (TLR) at 9- and 24-months with clinical results up to 36-months.. A total of 63 patients were enrolled. All patients underwent lesion pre-dilatation and 22 patients (34.9%) underwent post-dilatation. Clinical device and procedural success was 98.4% (62/63 patients) and 96.8% (61/63 patients) respectively. At 9-months, TVF occurred in 3/61 (4.9%) of the patients including 2 peri-procedural MI and one ischemia-driven TLR. Between 9- to 24-months, ischemia-driven TLR occurred in 3 additional patients (4.9%) including 1 patient who presented with very late ST after stopping all medications. There were no further TVF between 24- and 36-months.. In this multi-center prospective study, the FORTITUDE® BRS was shown to be safe and effective in the treatment of single coronary lesions with low levels of TVF and LLL at 9- and 24-months. It was shown to be clinically safe upto 36-months follow-up.

Topics: Absorbable Implants; Cardiovascular Agents; Colombia; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Italy; Molecular Weight; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Sirolimus-coated balloons (SCBs) represent a novel therapeutic option for both in-stent restenosis (ISR) and de novo coronary lesions treatment, especially in small vessels. Our registry sought to evaluate the procedural and clinical outcomes of such devices in a complex acute coronary syndrome (ACS) clinical setting.. In the SELFIE prospective registry, SCB showed a good safety and efficacy profile for the treatment of coronary lesions, both ISR and/or de novo in small vessels, in a complex ACS population of patients at the 11 ± 7 months follow-up.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Italy; Male; Outcome and Process Assessment, Health Care; Registries; Sirolimus; ST Elevation Myocardial Infarction

The goal of this study was to evaluate the performance of the Inspiron. It was a prospective, single-center registry. To represent clinical practice, all patients undergoing percutaneous coronary intervention were included in this registry. There were no exclusion criteria. Clinical follow-ups were performed at twelve months. The endpoints were the occurrence of all-cause death, definite stent thrombosis, and new revascularization.. Between November 2017 and May 2019, 790 patients were included (1067 lesions). The mean age was 60.42 ± 14.94 years, and 74.7% presented with acute coronary syndrome. Diabetes mellitus was present in 43.9% of patients, and previous myocardial infarction and previous percutaneous coronary intervention were present in 17.9% and 11.3%, respectively. Angiographic success was achieved in 99.1%. The incidence of all-cause death was 11.5% (6.2% in-hospital and 5.3% in the follow-up) and definitive stent thrombosis was 0.2%. New revascularization was performed in only 5.8% (target lesion revascularization: 2.2%; progression of disease in another lesion: 3.6%). Based on the multivariate regression analysis, only chronic renal failure was an independent predictor of adverse events (OR: 3.3; 95% CI: 1.22-8.92).. The result of this single-center registry demonstrates the safety and excellent performance of the Inspiron

Topics: Acute Coronary Syndrome; Biodegradable Plastics; Brazil; Chromium Alloys; Coated Materials, Biocompatible; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Registries; Reoperation; Sirolimus

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Male; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

To assess the performance of the commercially available Magmaris sirolimus-eluting bioresorbable scaffold (BRS) with invasive imaging at different time points.. Coronary BRS with a magnesium backbone have been recently studied as an alternative to polymeric scaffolds, providing enhanced vessel support and a faster resorption rate. We aimed to assess the performance of the commercially available Magmaris sirolimus-eluting BRS at different time points.. A prospective, single-center, nonrandomized study was performed at the Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands. Six patients with stable de novo coronary artery lesions underwent single-vessel revascularization with the Magmaris sirolimus-eluting BRS. Invasive follow-up including intravascular imaging using optical coherence tomography (OCT) was performed at different time points.. At a median of 8 months (range 4-12 months) target lesion failure occurred in one patient. Angiography revealed a late lumen loss of 0.59 ± 0.39 mm, a percentage diameter stenosis of 39.65 ± 15.81%, and a binary restenosis rate of 33.3%. OCT showed a significant reduction in both minimal lumen area (MLA) and scaffold area at the site of the MLA by 43.44 ± 28.62 and 38.20 ± 25.74%, respectively. A fast and heterogeneous scaffold degradation process was found with a significant reduction of patent struts at 4-5 months.. Our findings show that the latest iteration of magnesium BRS suffers from premature dismantling, resulting in a higher than expected decrease in MLA.

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Female; Humans; Magnesium; Male; Middle Aged; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Sirolimus; Thrombosis; Treatment Outcome

Edge restenosis has gained attention as a main cause of restenosis after first-generation drug-eluting stent (DES) implantation. The aim of this study was to assess the incidence of edge restenosis and identify the predictors of edge restenosis after second-generation DES implantation. Data were obtained from several postmarketing surveillance (PMS) studies on a cobalt-chromium everolimus-eluting stent (CoCr-EES; Xience V/PROMUS, Xience Prime, Xience Prime SV, and Xience Expedition SV), a second-generation DES, in Japan. Angiographic analysis was conducted at the baseline and after eight months on the following subsegments: in-stent region, proximal edge, and distal edge. Restenosis was defined as ≥ 50% diameter stenosis (DS) at follow-up. We used multivariate logistic regression (with lesions as a random effect) to compare the instances of restenosis between the proximal and the distal edges. Univariate and multivariate analyses of the risk factors for restenosis were performed for each subsegment. We analyzed 1,966 lesions in 1,687 patients. The restenosis rates at the in-stent region, proximal edge, and distal edge were 4.4%, 3.0%, and 1.1%, respectively. The risk of restenosis at the distal edge was significantly lower than that at the proximal edge, when adjusted for 13 variables. The predictors of restenosis were postprocedural % diameter stenosis (%DS), postprocedural reference diameter, ≥ 45° bending, stent overlap at the proximal edge, and postprocedural %DS at the distal edge. Our analysis of eight-month angiographic outcomes from CoCr-EES PMS demonstrated that postprocedural %DS is a major predictor of edge restenosis. Edge restenosis is more likely attributable to postprocedural angiographic results than to the patient's background.

Topics: Age Factors; Aged; Angioplasty, Balloon, Coronary; Chromium; Cobalt; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Equipment Failure Analysis; Female; Hospitals, University; Humans; Incidence; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Product Surveillance, Postmarketing; Prognosis; Prosthesis Design; Registries; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Sirolimus; Survival Analysis; Treatment Outcome

Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) usually involves multiple overlapping stents implantation to cover long coronary segments. A higher rate of restenosis has been described with stent overlapping. Recently, new long tapered stents emerged as a potential tool for treating long coronary lesions. Feasibility of using these new devices for the CTO PCI has not been described. The aim of this work was to describe our initial experience with 50 and 60 mm-long tapered sirolimus-eluting stents (SES) in CTO PCI.. We included 54 consecutive patients who underwent a CTO PCI and in whom an attempt to implant a 50 or 60 mm-long tapered SES was performed. Baseline clinical, angiographic, and procedural characteristics were recorded.. The median (IQR) age was 64 (58-73) years, and 45 (83.3%) patients were male. The tapered SES 50 and 60 mm-long was successfully implanted in 51 (94.4%) patients. In three patients, a 60 mm-long stent could not be implanted, and two or three overlapped shorter drug-eluting stents were deployed instead. An average of 1.4 ± 0.6 stents per patient was implanted. A single stent was deployed in 32 (59.3%) patients. During a median follow-up of 330 (149-551) days, repeat PCI in the target vessel was performed in two patients.. The use of the new BioMime Morph™ tapered SES for the treatment of CTO appears to be feasible in a high proportion of procedures. Further studies confirming the feasibility of this approach and its potential clinical advantages are needed.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome; Vascular Patency

Topics: Automobiles; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus; Treatment Outcome

To evaluate the angiographic performance of a novel sirolimus-coated balloon (SCB) in de novo coronary lesions.. Out of an all-comer prospective registry of patients treated with the SCB at our center from April 2016 to September 2017, we selected those treated for a de novo stenosis on a native vessel, with a scheduled angiographic control at at least 4 months after the index procedure. We performed a centralized, blinded core-lab adjudicated quantitative coronary angiography analysis. Primary endpoint was late lumen loss. Secondary endpoints were binary restenosis and target-lesion revascularization.. A total of 27 patients with native coronary arteries treated with SCB and with angiographic follow-up entered the study; seven patients were excluded because a stent was implanted at the lesion site during the index procedure. The degree of calcification (assessed with coronary angiography) was high in six patients (30%) and the average lesion length was 20.52 ± 6.88 mm. The reference vessel diameter was 2.32 ± 0.44 mm and the percentage diameter stenosis was 67 ± 12. Procedural success was obtained in all patients. After a median of 6.6 ± 2.5 months, late lumen loss was 0.09 ± 0.34 mm and the percentage diameter stenosis was 31 ± 18. We observed two cases (10%) of binary restenosis which underwent subsequent target-lesion revascularization: in one a drug-eluting stent was implanted, whereas the other patient was treated with paclitaxel-coated balloon. No myocardial infarction or death was observed during follow-up.. The use of a novel SCB in native coronary arteries was associated with good angiographic outcome at 6-month follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Female; Humans; Italy; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Background A novel bioresorbable scaffold, the sirolimus-eluting Fantom, incorporates a radiopaque polymer, struts with a thickness of 125 µm, and a crossing profile of 1.35 mm. The purpose of this study was to evaluate the 9-month angiographic and 12-month clinical outcomes of the FANTOM scaffold in a larger patient population. Methods and Results The FANTOM II study (Safety & Performance Study of the Fantom Sirolimus-Eluting Bioresorbable Coronary Scaffold - First Report on Initial 24 Month Outcomes) was a prospective, multicenter trial which enrolled 240 patients with single de novo coronary stenosis with reference vessel diameter 2.5 to 3.5 mm diameter and lesion length ≤20 mm. Major adverse cardiac events through 12-month follow-up were assessed. Angiographic follow-up was performed in consecutive patient cohorts at 6 months (n=117) and 9 months (n=123). Acute delivery success, acute technical success, acute procedural success, and clinical procedural success rates as defined in the clinical protocol were 97.9% (235/240), 95.8% (230/240), 99.1% (228/230), and 99.6% (227/228), respectively. The mean in-stent late lumen loss at 6 months and 9 months were 0.25±0.40 mm and 0.33±0.36 mm, respectively, and in-segment binary restenosis occurred in 2.0% and 7.6% of patients, respectively. Major adverse cardiac events and target lesion failure through 12 months occurred in 4.2% of 240 patients; scaffold thrombosis developed in only one patient (0.4%). Conclusions The Fantom sirolimus-eluting bioresorbable coronary scaffold demonstrated favorable safety and effectiveness performance at 12-month follow-up. Longer-term follow-up is ongoing to examine the late outcomes with this novel device. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02539966.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

Although drug-eluting stents (DES) have outclassed the use of bare metal stents, the safety and efficacy of DES at long-term follow-up has still been conflicting because of increased occurrence of late or very late restenosis and stent thrombosis after DES implantation. Hence, the present study was aimed to evaluate the 3-year safety and clinical performance of biodegradable polymer-coated ultra-thin (60 µm) sirolimus-eluting stent (SES) in real-world patients with coronary artery disease (CAD).. This was a physician-initiated, retrospective, single-centre, observational study that included 237 consecutive patients who had previously undergone implantation of only Supraflex SES (Sahajanand Medical Technologies Pvt Ltd, Surat, India) for the treatment of CAD. Follow-up was received after 1 year and 3 years of stent implantation. The primary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and target lesion revascularisation (TLR). Stent thrombosis was considered as a safety endpoint.. The mean age of patients was 64.1 ± 10.2 years, and 192 (81.0%) patients were male. The average stent length and diameter were 24.4 ± 9.0 mm and 3.1 ± 0.4 mm, respectively. The cumulative MACE rate at 3 years follow-up was 6.5% which included 4 (1.8%) cardiac deaths, 6 (2.8%) MI, and 4 (1.8%) TLR. There were 2 (0.9%) cases of stent thrombosis.. Treatment of patients with CAD in real-world clinical practice was associated with sustained clinical safety and low rates of restenosis, stent thrombosis and MACE up to 3 years after Supraflex SES implantation.

Topics: Aged; Biodegradable Plastics; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; India; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Sirolimus; Survival Analysis

Patients with diabetes mellitus (DM) remain at higher risk of restenosis after percutaneous coronary intervention despite the use of contemporary drug-eluting stents. The Cre8 amphilimus-eluting stent (AES) has shown promising results in DM patients. Whether this holds true irrespective of patient's clinical and angiographic complexity is unknown.. Five hundred and ninety five consecutive patients (738 lesions) undergoing AES implantation were included in the INVESTIG8 multicenter registry. Patients were stratified according to DM status and further stratified according to patients' complexity. The prespecified primary endpoint was target lesion failure (TLF)-defined as the composite of cardiac death, target-vessel myocardial infarction, and target lesion revascularization (TLR).. DM patients were more often complex as compared to non-DM patients (70% vs. 61%, P = 0.015). At 18-month follow-up, there was a trend to a higher TLF rate in DM than in non-DM patients (6.9% vs. 3.5%, P = 0.063). This was largely driven by a markedly higher risk of TLF among complex DM patients as compared to simple DM patients (8.9% vs. 2.4%, P = 0.053). A multivariate analysis identified complexity (HR 6.11, 95% CI: 1.42-26.2) but not DM (HR 1.59; 95% CI 0.71-3.56) as an independent predictor of TLF. Of note, TLR rates were similar between DM and non-DM patients (3.3% vs. 1.9%, P = 0.228).. In this real-world, multicenter registry the Cre8 AES showed favorable clinical outcomes in DM patients. Increased risk of TLF appears to be driven by patients' complexity rather than DM status. These findings will need to be confirmed in a large-scale randomized trial.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Europe; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prosthesis Design; Recurrence; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

This study aimed at assessing the performance of a new generation polymer-free biolimus-eluting stent (BES) in real-world patients with ST-segment elevation myocardial infarction (STEMI).. Polymers components of early-generation drug-eluting stents have been implicated in the pathogenesis of delayed arterial healing, vessel remodeling, and delayed stent thrombosis. Recently, a novel polymer-free BES has shown excellent clinical performance in clinical trial setting.. Overall, 175 consecutive patients (64 ± 14 years, 141 men) treated with the BioFreedom (Biosensors Europe, Morges, Switzerland) polymer-free BES because of STEMI were included in this study. The primary endpoint was the rate of major adverse cardiac events (MACE), a composite of cardiac death, recurrent myocardial infarction, and ischemia-driven target vessel revascularization at 1 year follow-up. A subgroup of patients underwent 6-month angiographic follow-up. Dual antiplatelet therapy was prescribed for 12 months after STEMI.. At 1 year, the cumulative rate of MACE was 4.6%. One patient (0.6%) had an arrhythmic cardiac death and five (2.9%) had ischemia-driven target vessel revascularization, although only three (1.7%) had target lesion revascularization. Two (1.1%) patients had acute stent thrombosis yielding nonfatal myocardial infarction. In 70 patients (63 ± 14 years, 61 men), quantitative coronary angiography at 6-month follow-up revealed diameter stenosis of 24.1 ± 13.7% and minimal lumen diameter of 2.29 ± 0.56 mm, yielding a late lumen loss of 0.13 ± 0.14 mm.. In real-world setting, implantation of a new-generation polymer-free BES during STEMI is associated with favorable clinical and angiographic results, pointing toward the overall efficacy and safety of the device in complex clinical scenarios.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Hospitals, Public; Hospitals, Urban; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Recurrence; Registries; Risk Factors; Rome; Sirolimus; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome

To assess clinical outcomes of Amphilimus Sirolimus-Eluting Stents (A-SES) as compared to Zotarolimus-Eluting Stents (ZES) in complex real-world diabetic patients.. Patients with diabetes mellitus represent one of the most challenging scenarios with high rates of restenosis and stent thrombosis in the current era of drug-eluting stents. Hence, we assessed the safety of A-SES versus ZES in complex diabetic patients.. In this observational study, we analyzed all consecutive patients with diabetes mellitus referred to our center from November 2012 to November 2014. The primary outcome was target-lesion failure at 1-year follow-up.. A total of 165 consecutive diabetic patients underwent percutaneous coronary intervention with A-SES or ZES for stable coronary artery disease in our tertiary center. Using the Kaplan Meier method the cumulative incidence of target-lesion failure was 6.7% (5.9% A-SES versus 7.5% ZES, p=0.19) at 1-year follow-up. Event-free survival at 1year follow-up was similar (89.4% A-SES vs. 83.3% ZES, p=0.29). Interestingly, we did not find any cases of definite-, and only one case of probable stent thrombosis in this high risk cohort.. In this real-world registry, A-SES and ZES seems to be associated with promising 1-year clinical safety outcomes following PCI in a contemporary cohort of high-risk diabetic patients. Our results should be considered hypothesis generating, as the clinical safety of A-SES has to be confirmed in a large trial.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Netherlands; Percutaneous Coronary Intervention; Progression-Free Survival; Prosthesis Design; Registries; Retrospective Studies; Risk Factors; Sirolimus; Time Factors

Traditional coronary drug-eluting stents (DES) are made from metal and are coated with a permanent polymer film containing an anti-proliferative drug. Subsequent to stent deployment in a diseased coronary artery, the drug releases into the artery wall and helps prevent restenosis by inhibiting the proliferation of smooth muscle cells. Although this technology has proven to be remarkably successful, there are ongoing concerns that the presence of a polymer in the artery can lead to deleterious medical complications, such as late stent thrombosis. Polymer-free DES may help overcome such shortcomings. However, the absence of a rate-controlling polymer layer makes optimisation of the drug release profile a particular challenge. The use of microporous stent surfaces to modulate the drug release rate is an approach that has recently shown particularly promising clinical results. In this study, we develop a mathematical model to describe drug release from such stents. In particular, we develop a mathematical model to describe drug release from microporous surfaces. The model predicts a two-stage release profile, with a relatively rapid initial release of most of the drug, followed by a slower release of the remaining drug. In the model, the slow release phase is accounted for by an adsorption/desorption mechanism close to the stent surface. The theoretical predictions are compared with experimental release data obtained in our laboratory, and good agreement is found. The valuable insights provided by our model will serve as a useful guide for designing the enhanced polymer-free stents of the future.

Topics: Antibiotics, Antineoplastic; Coronary Disease; Coronary Restenosis; Drug Liberation; Drug-Eluting Stents; Humans; Microscopy, Atomic Force; Models, Biological; Percutaneous Coronary Intervention; Porosity; Sirolimus; Surface Properties

Topics: Absorbable Implants; Coronary Restenosis; Drug Carriers; Humans; Male; Middle Aged; Prostheses and Implants; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence

Early-generation drug-eluting stents (DESs) have been shown to accelerate neoatherogenesis. Limited optical coherence tomography (OCT) data on the very long-term neoatherosclerotic progression after DES implantation are available.. The aim of this study was a serial OCT evaluation of neoatherosclerosis at three and nine years after implantation of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs).. Consecutive patients undergoing elective percutaneous coronary intervention with SES (Cypher, Cordis) or PES (Taxus, Boston Scientific) were included in this single-centre, longitudinal study. OCT analysis was performed after three and nine years by an independent core laboratory.. A total of 39 OCT recordings were assessed at three years after the index procedure; of them, 22 (eight SES and 14 PES) OCT pullbacks were evaluated in a paired analysis at three and nine years post implantation. Overall, neoatheroscle-rosis was identified in 23.1% of stents at three years and in 30.8% at nine years after the index procedure (p = 0.289). No features of significant neoatherosclerotic progression were found in either group between three- and nine-year assessment.. At nine years after implantation of early-generation DES no significant neoatherosclerotic progression was observed among patients with uneventful follow-up at three years after PCI, as assessed by OCT. These observations need to be confirmed in larger studies including the current generation of DESs.

Topics: Aged; Atherosclerosis; Coronary Artery Disease; Coronary Restenosis; Disease Progression; Drug-Eluting Stents; Female; Humans; Longitudinal Studies; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Postoperative Period; Sirolimus; Tomography, Optical Coherence

Drug-eluting stents are the most commonly employed method to control post-angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent thrombosis because of endothelium damage caused by both drug and stenting. To solve this major medical problem, an endothelium-protective and stent-free anti-restenotic method is highly desirable. Here we have generated a biomimetic intravenous delivery system using dendritic polymer-based nanoclusters, which were coated with platelet membranes for targeting to the injured arterial wall where restenosis occurs. These nanoclusters were loaded with an endothelium-protective epigenetic inhibitor (JQ1) or an endothelium-toxic status quo drug (rapamycin), and compared for their ability to mitigate restenosis without hindering the process of re-endothelialization. Fluorescence imaging of Cy5-tagged biomimetic nanoclusters indicated their robust homing to injured, but not uninjured arteries. Two weeks after angioplasty, compared to no-drug control, both rapamycin- and JQ1-loaded biomimetic nanoclusters substantially reduced (by >60%) neointimal hyperplasia, the primary cause of restenosis. However, whereas the rapamycin formulation impaired the endothelial re-coverage of the denuded inner arterial wall, the JQ1 formulation preserved endothelial recovery. In summary, we have created an endothelium-protective anti-restenotic system with biomimetic nanoclusters containing an epigenetic inhibitor. This system warrants further development for a non-thrombogenic and stent-free method for clinical applications.

Topics: Animals; Azepines; Biomimetic Materials; Carotid Arteries; Carotid Artery Injuries; Coronary Restenosis; Drug-Eluting Stents; Endothelium, Vascular; Humans; Male; Nanoparticles; Neointima; Rats, Sprague-Dawley; Sirolimus; Triazoles

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus; Stents

Although rapamycin is a well-known conformational inhibitor of mTORC1, it is now widely used for treating arterial restenosis. Various rapamycin analogues (rapalogue) have been made for applying to drug-eluting stents. Here we show that two major rapalogues, everolimus and biolimus, exert a differential effect on the mTORC1-mediated signaling pathways in vascular smooth muscle cells. In balloon-injured carotid arteries, both rapalogues strongly inhibit neointimal hyperplasia. Signaling pathway analyses reveal that everolimus exert cytotoxicity by increasing cellular reactive oxygen species and consequently reduce energy metabolism. By contrast, biolimus confers a preferential induction of autophagy by more strongly activating major autophagy regulator, ULK1, in vascular smooth muscle cells than everolimus does. As a consequence, the implantation of biolimus-eluting stent reduces endothelial loss, which in turn reduces inflammation, in porcine coronary arteries. Thus, this study reveals that a chemical derivatization can cause a change among mTORC1-dependent signaling pathways in vascular smooth muscle cells, thereby enabling to elicit a differential efficacy on arterial restenosis.

Topics: Animals; Autophagy; Autophagy-Related Protein-1 Homolog; Cell Survival; Cells, Cultured; Coronary Restenosis; Drug-Eluting Stents; Energy Metabolism; Humans; Intracellular Signaling Peptides and Proteins; Macrolides; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphorylation; Rats; Sirolimus; Swine

Topics: Absorbable Implants; Acute Coronary Syndrome; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Polymers; Sirolimus

Long coronary artery lesions are increasingly treated with new technologies including current generation drug eluting stents (DES) despite a lack of robust data on outcomes. In the current study, patients receiving Xience V DES for very long lesions (>35 mm) compared to lesions 25-35 mm had similar outcomes. Future research should address late outcomes, stent thrombosis rates, as well as investigation of lesions greater than 60 mm.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome

Topics: Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus; Stents; Treatment Outcome

New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries.. We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later.. The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls.. In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES.

Topics: Absorbable Implants; Animals; Antibiotics, Antineoplastic; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Metals; Neointima; Polymers; Prosthesis Design; Random Allocation; Sirolimus; Stents; Sus scrofa; Swine; Treatment Outcome

The third generation drug eluting Orsiro stent had shown already promising results in non-complex lesions.. We evaluated angiographic and 24 month clinical results of the sirolimus eluting Orsiro stents (O-SES) after recanalization of coronary chronic total occlusions (CTO). Results were compared with the zotarolimus eluting Resolute Integrity (R-ZES).. In a prospective series 57 patients were treated with a R-ZES followed by 74 patients treated with a O-SES stent. Angiographic follow up after 9 months and clinical follow-up after 12 and 24 months was performed.. In-stent late lumen loss was 0.24±0.53 mm for the O-SES compared with 0.59±0.72 (P=0.01) for R-ZES. Rates for TLR were similar (O-SES 10.0% versus R-ZES 11.1%, P=0.84). There was no definite stent thrombosis.. The O-SES resulted in a significant lower late lumen loss but with similar clinical results up to 24 month compared to the R-ZES after treatment of CTO lesions.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Transplant vasculopathy is a form of slowly progressive rejection. The interventional cardiologist plays an important role in maintaining survival of this precious commodity by performing PCI. Everolimus drug eluting stents are highly effective and have relatively low occurrence of in-stent restenosis, but transplant vasculopathy continues to progress in a diffuse pattern.

Topics: Allografts; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Heart Transplantation; Humans; Percutaneous Coronary Intervention; Sirolimus; Stents; Treatment Outcome

The purpose of this study was to evaluate the outcomes of the novel Fantom coronary bioresorbable scaffold at 6 months.. The Fantom sirolimus-eluting bioresorbable scaffold incorporates a unique proprietary iodinated, polycarbonate copolymer of tyrosine analogs that is radiopaque, with thin struts (125 μm) that facilitate device delivery and precise target lesion treatment.. The 6-month outcomes and performance of the Fantom scaffold were evaluated in 117 patients with single de novo native coronary artery lesions of length ≤20 mm and reference vessel diameter 2.5 to 3.5 mm. The primary angiographic endpoint was mean late lumen loss at 6 months measured by quantitative coronary angiography. Procedural outcomes were categorized as short-term technical success, short-term procedural success, and clinical procedural success. The primary clinical endpoint was major adverse cardiac events at 6 months, the composite of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (TLR).. Short-term technical success, short-term procedural success, and clinical procedural success were achieved in 96.6%, 99.1%, and 99.1% of patients, respectively. Mean 6-month in-stent late lumen loss was 0.25 ± 0.40 mm (n = 100). Binary restenosis was present in 2 patients (2.0%). Major adverse cardiac events within 6 months occurred in 3 patients (2.6%), including no deaths, 2 MIs, and 2 TLRs (1 patient had both an MI and TLR). Scaffold thrombosis occurred in 1 patient (0.9%).. The clinical results from 117 patients enrolled in cohort A of the multicenter FANTOM II (Safety & Performance Study of the FANTOM Sirolimus-Eluting Bioresorbable Coronary Scaffold) study demonstrate favorable 6-month outcomes of this novel device in the treatment of noncomplex coronary artery disease.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Female; Humans; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon; Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus; Stents

Topics: Coronary Restenosis; Everolimus; Humans; Polymers; Sirolimus; Stents

This study aimed to evaluate the efficacy and safety of limus-based drug-eluting stent (DES) implanted in medium or small coronary vessels during a very long-term follow-up period.. A total of 2383 patients treated with 2916 limus-based DES between April 2003 and March 2015 were evaluated. The enrolled patients were stratified into 3 groups according to the reference vessel diameter: group A: ≤2.5 mm; group B: 2.51 to 3.00 mm; group C: 3.01 to 3.50 mm.. Group A had a significantly higher loss index and binary restenosis rate than the other 2 groups at 9 months of angiographic follow-up. Group A also had a significantly higher rate of target lesion revascularization and a lower rate of major adverse cardiovascular event-free survival than the other 2 groups after a follow-up period of 68 ± 59 months. The long-term cardiovascular event-free survival curves based on a Cox regression model showed large vessel size, and second-generation DES had better outcomes.. An inverse relationship between vessel size (≤3.5 mm) and clinical outcomes was noted in patients who received limus-based DES implantation.

Topics: Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Electrocardiography; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Factors; Sirolimus; Survival Rate; Treatment Outcome

This is the first documented case of a drug-coated balloon strategy for the treatment of bioresorbable in-scaffold restenosis caused by diffuse neointimal proliferation. This case can provide an alternative treatment option in this setting, avoiding potential problems related to further bulky metallic stents in a patient where a different strategy was initially planned. © 2016 Wiley Periodicals, Inc.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Male; Prosthesis Design; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence; Ultrasonography, Interventional

Endothelial shear stress (ESS) may play a key role in the pathobiology of stent restenosis (SR). Nevertheless, limited data are available about ESS and its relation to SR.. We enrolled 14 patients who underwent successful percutaneous coronary intervention (PCI) in this study. Three-dimensional (3D) reconstruction of 14 coronary arteries before and after stent implantation was performed. Using computational fluid dynamics, mean ESS was calculated proximally, in tertiles within and distal to the stent, both before and after stent implantation.. Stent implantation resulted in a significant ESS decrease in the entire atherosclerotic lesion (1.83 vs. 1.26 Pa, p = 0.02). Regarding the five territories in which the entire lesion was divided, ESS decrease was marginally significant in the area of the second in-stent tertile, and in the area 5 mm distal to the stent, whereas ESS decrease was not significant in the area 5 mm proximal to the stent, and in the area of the first and third in-stent tertile. At 12 months, two patients had SR, but restenosis was not related to ESS decrease.. ESS decreases after stent implantation but not uniformly, with the major reduction being in the middle tertile of the stent, and distal to the stent. In-stent ESS decrease may create local hemodynamic conditions leading to in-stent and in-segment restenosis.

Topics: Algorithms; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Elastic Tissue; Endothelium, Vascular; Follow-Up Studies; Hemodynamics; Humans; Hydrodynamics; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Patient-Specific Modeling; Percutaneous Coronary Intervention; Shear Strength; Sirolimus

Our aim was to investigate whether long-term (three-year) clinical outcomes after multivessel treatment with the Resolute zotarolimus-eluting stent (R-ZES) were similar to single-vessel treatment.. The RESOLUTE Global Clinical Trial Program enrolled 7,618 patients, of whom 1,562 underwent multivessel and 6,053 single-vessel treatment with the R-ZES. Patients in the multivessel group were more likely to have complex lesions (58% vs. 44%, p<0.001). Clinical outcomes were compared using a Cox regression model adjusted by propensity score to account for differences in baseline characteristics. Compared with single-vessel treatment, multivessel treatment was associated with more complex anatomy and longer mean total stent length (57.8±28.6 vs. 26.7±15.2 mm, p<0.001). At three years, the cumulative incidence of target lesion failure was similar in patients with multivessel and single-vessel treatment (11.0% vs. 9.1%, adjusted p=0.986), as was the incidence of cardiac death or target vessel myocardial infarction (6.7% vs. 5.7%, adjusted p=0.793), the incidence of clinically driven target lesion revascularisation (5.1% vs. 4.4%, adjusted p=0.904), and the incidence of Academic Research Consortium definite or probable stent thrombosis (1.2% vs. 0.9%, adjusted p=0.544).. Multivessel treatment with R-ZES provided good long-term clinical outcomes that were comparable to those achieved with single-vessel stenting, supporting the efficacy and safety of R-ZES in patients in this setting.

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

To develop an ameliorated sirolimus (SIR) liposome for intramural delivery, the effects of various carrier physicochemical parameters on the antirestenosis efficacy were evaluated.. Different liposomes were prepared, characterized and administered to balloon injured rats (12 animal groups). Their efficacies were investigated using morphometric, immunohistochemical and in vivo computed tomography imaging analyses.. The antirestenosis efficacy of SIR liposomes decreased in the following order: cationic 100 nm vesicles ≥ cationic 60 nm vesicles > neutral 100 nm vesicles ≥ stealth 100 nm vesicles > anionic 100 nm vesicles. The 100 µg SIR loaded in cationic liposomes showed almost no artery stenosis.. Appropriate modulation of physicochemical characteristics makes it possible to optimize the liposomes for local delivery.

Topics: Animals; Cardiovascular Agents; Carotid Arteries; Carotid Artery Injuries; Coronary Restenosis; Ki-67 Antigen; Liposomes; Male; Neointima; Plasma; Polysorbates; Rats; Rats, Sprague-Dawley; Sirolimus

In this study, sirolimus (SRL) was loaded within biomimetic apatite formed on cobalt-chromium (Co-Cr) alloy, which has been reported for the first time, to inhibit the in-stent restenosis. Two different groups of loading SRL within biomimetic apatite were prepared: Group A (mono-layer of apatite/SRL) and Group B (bi-layer of apatite/SRL). Group A and Group B showed the biphasic pattern of SRL release up to 40 and 90days, respectively. The attachment of human artery smooth muscle cell (HASMC) for both Group A and Group B was significantly inhibited, and proliferation dramatically decreased with the release of SRL. Noteworthily, biomimetic apatite alone also suppressed the SMC proliferation. The porous biomimetic apatite uniformly covered Co-Cr stent without crack or webbings. After balloon expansion, the integrity of biomimetic apatite was sufficient to resist delamination or destruction. Thus, this study demonstrated that biomimetic apatite is a promising drug carrier for potential use in stents.

Topics: Apatites; Arteries; Biomimetic Materials; Cell Adhesion; Cell Proliferation; Chromium Alloys; Cobalt; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; Myocytes, Smooth Muscle; Polymers; Porosity; Sirolimus; Surface Properties; X-Ray Diffraction

Previous studies have demonstrated that patients with small coronary artery lesions are at increased risk for late cardiac events after percutaneous coronary intervention. It remains uncertain whether second-generation drug-eluting stents have an advantage over first-generation drug-eluting stents in patients with small vessel lesions. Our aim was to compare in the 3-year clinical impact between second-generation everolimus-eluting stents (EES) and first-generation sirolimus-eluting stents (SES) in small vessel lesions. Four-hundred forty-four patients with small vessel lesions defined as reference diameter <2.5 mm were treated with EES (237 patients, 265 lesions) or SES (207 patients, 220 lesions) and completed 3-year follow-up. We compared the major adverse clinical events (MACE) between the two groups. EES had no significant impact on the MACE rate compared with SES (4.6 vs. 7.2%, p = 0.14). No significant differences were observed in the individual components of cardiac death (1.7 vs. 1.9%, p = 0.78), myocardial infarction (1.3 vs. 3.4%, p = 0.12), and ischemia-driven target lesion revascularization (2.3 vs. 4.6%, p = 0.13) in EES and SES, respectively. Stent thrombosis, however, was significantly less in the EES group than in the SES group (0.7 vs. 3.4%, HR: 0.53, 95% CI 0.38-0.88, p < 0.05). EES implantation did not significantly impact 3-year MACE rates compared to SES implantation in small vessel lesions. A significant reduction in the overall rate of stent thrombosis was observed in recipients of EES. While the SES group showed increasing rates of late and very late thrombosis, the EES group did not. EES offers a safe and effective treatment for small vessel lesions.

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Revascularization; Percutaneous Coronary Intervention; Regression Analysis; Retrospective Studies; Risk Factors; Sirolimus; Treatment Outcome

Topics: Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome

Topics: Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome

Topics: Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome

A 70-year-old man underwent stent implantation for right coronary artery (RCA) lesions with a bare metal stent (BMS) and two sirolimus-eluting stents (SES). However, as both the BMS and SES stented sites developed restenosis after 13 months, he underwent target lesion revascularization using directional coronary atherectomy (DCA). On histopathology, the restenosis lesion at the SES-deployed site showed greater inflammation and less re-endothelialization than that at the BMS-deployed site. Three months later, the SES-deployed site developed a second restenosis, in which paclitaxel-eluting stents (PES) were implanted (PES-in-SES), while the BMS-deployed site was restenosis free. Five years later, restenosis was absent in these RCA lesions. However, by optical coherence tomography and/or coronary angioscopy, the PES-in-SES site in the RCA showed poor neointimal coverage over the stent struts and yellowish neointima, suggesting lipid-rich neoatheroma formation, whereas at the BMS site appropriate white neointima formation was observed. Drug-eluting stents still have problems of persistent inflammation, inappropriate neointima formation, and neoatherosclerosis. Although we are now in the era of second generation DESs in which better stent performance would be promising, we should remember that we are obliged to continue to follow-up all patients in whom first generation DESs such as SES or PES have been placed.

Topics: Aged; Angioscopy; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Immunohistochemistry; Male; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Retreatment; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

We aimed to comprehensively evaluate poly-lactide polymer degradation and sirolimus release kinetics from a drug-eluting stent matrix in the in vivo setting using a nuclear magnetic resonance (NMR) method.. In 22 domestic swine, 18 biodegradable polymer-only coated stents (BPSs) and 36 biodegradable polymer-coated sirolimus-eluting stents (BP-SES) were implanted in coronary arteries with 115% overstretch. The animals were sacrificed at 1, 3, 7, 14, 28, and 56 days following baseline procedures. Vessel segments with BPS were harvested to evaluate polymer degradation with a NMR method, whereas BP-SES to analyze sirolimus tissue uptake and retention. Additionally, 8 BP-SES were implanted for histological analysis for 90 days of follow-up.. The NMR showed a gradual absorption of the polymer over the 6 consecutive time points, from 5.48 µg of the polymer on the stent at 1-day follow-up, through 4.33 µg at 3 days, 3.16 µg at 7 days, 2.42 µg at 14 days, 1.92 µg at 28 days to 1.24 µg in the last day of the study. The curve of polymer degradation corresponds well with the pharmacokinetic profile of sirolimus eluted from its surface and measured at identical time points. In histopathology, at 90 days, complete healing and biocompatibility were reported.. The utilization of NMR method for BP absorption kinetics evaluation is a useful tool, which may be widely adopted to test other biodegradable implants. Further, it may substantially improve their safety and efficacy by facilitating programmed polymer and drugs elution.

Topics: Absorbable Implants; Animals; Cardiovascular Agents; Coronary Restenosis; Disease Models, Animal; Drug-Eluting Stents; Female; Magnetic Resonance Spectroscopy; Male; Percutaneous Coronary Intervention; Polyesters; Prosthesis Design; Sirolimus; Sus scrofa

We aimed to evaluate the long-term safety and efficacy of the STENTYS self-apposing paclitaxeleluting stent (STENTYS-PES) in bifurcation lesions in routine clinical practice.. The primary endpoint of the study was the composite major adverse cardiac events (MACE: cardiac death, myocardial infarction, clinically driven target lesion revascularisation, or emergent bypass surgery) assessed at six months after enrolment. This was reported in 21 patients (10.1%), mainly due to clinically driven target lesion revascularisation (TLR). At 12 months, 27 patients experienced MACE (13.0%).. The long-term results of OPEN II show that the STENTYS-PES is safe and effective in the treatment of all-comers with coronary bifurcation lesions.

Topics: Aged; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Risk Factors; Sirolimus; Time; Treatment Outcome

Overall stent performance should be characterized by geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. The aim of this study was to compare the performance of zotarolimus-eluting stent (ZES), everolimus-eluting stent (EES) and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscopy. For 36 stented coronary lesions (BMS, 12 lesions; ZES, 11 lesions; EES, 13 lesions) in 27 patients, we calculated neointimal area and uncovered stent strut rate based on OCT findings at 10 months after stent placement. The grades of neointimal coverage and yellow color, both of which were classified from 0 to 3, were also assessed by coronary angioscopy. The plaque area of the ZES lesions was larger than that of the EES lesions (P < 0.05) but smaller than that of the BMS lesions (P < 0.05). The OCT-based uncovered rate of the ZES lesions was less than that of the EES lesions (P < 0.01), but similar to that of the BMS lesions. The stent coverage grade by angioscopy was higher in the ZES lesions than in the EES lesions (P < 0.05), but similar to the BMS lesions. The yellow grade was less in the ZES lesions than in the EES lesions (P < 0.01), but similar to the BMS lesions. ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as prevention of neoatheroma formation. ZES may have superior performance compared with EES.

Topics: Aged; Angioscopy; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Sirolimus; Tomography, Optical Coherence

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Myocardial Infarction; Sirolimus; Stents; Treatment Outcome

Among antirestenotic compounds, sirolimus displays a superior safety profile compared to paclitaxel, but its pharmacokinetic properties make it a challenging therapeutic candidate for single-time delivery. Herein we evaluate the feasibility of delivery, long-term retention and vascular effects of sirolimus nanoparticles delivered through a novel porous angioplasty balloon in normal porcine arteries and in a swine model of in-stent restenosis (ISR).. Sirolimus nanoparticle formulation was delivered via porous balloon angioplasty to 753 coronary artery segments for pharmacokinetic studies and 26 segments for biological effect of sirolimus delivery in different clinical scenarios (de novo [n=8], ISR [n=6] and following stent implantation [n=12]). Sirolimus coronary artery concentrations were above the target therapeutic level of 1 ng/mg after 26 days, and were >100-fold higher in coronary artery treatment sites than in distal myocardium and remote tissues at all time points. At 28 days, reduction in percent stenosis in formulation-treated sites compared to balloon angioplasty treatment was noted in all three clinical scenarios, with the largest effect seen in the de novo study.. Local coronary delivery of sirolimus nanoparticles in the porcine model using a novel porous balloon delivery system achieved therapeutic long-term intra-arterial drug levels without significant systemic residual exposure.

Topics: Angioplasty, Balloon, Coronary; Animals; Antibiotics, Antineoplastic; Coronary Restenosis; Coronary Vessels; Female; Male; Nanoparticles; Sirolimus; Swine

The aim of this study was to assess prospectively the effectiveness and safety of a new version of the dedicated bifurcation BiOSS stent, the sirolimus-eluting BiOSS LIM, for the treatment of distal left main (LM) stenosis.. This was a prospective international registry which enrolled patients with NSTE-ACS or stable angina. Provisional T-stenting was the mandated strategy. The primary endpoint was the cumulative rate of cardiac death, myocardial infarction (MI) and target lesion revascularisation (TLR) at 12 months. Twelve-month quantitative coronary angiography endpoints included late lumen loss and percent diameter stenosis. A total of 74 patients with distal LM stenosis were enrolled. Seventy-three of the 74 patients (aged 67±9 years, 23% women, 20.3% NSTE-ACS, SYNTAX score 22.4±4.4) were successfully treated with the BiOSS LIM stent, with additional side branch placement of regular DES in 11 patients (14.9%). Periprocedural MI occurred in one (1.4%) patient. The 12-month MACE rate was 9.5% without cardiac death or definite stent thrombosis. TLR and MI rates were 6.8% (n=5) and 2.7% (n=2), respectively.. The use of the BiOSS LIM dedicated bifurcation stent for the treatment of distal LM stenosis was feasible and safe, with promising long-term clinical effectiveness.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Constriction, Pathologic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Prospective Studies; Registries; Sirolimus; Time; Treatment Outcome

Absorbable scaffolds were designed to overcome the limitations of conventional, non-absorbable metal-based drug-eluting stents. So far, only polymeric absorbable scaffolds are commercially available. We aimed to assess the safety and performance of a novel second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in patients with de-novo coronary artery lesions.. We did this prospective, multicentre, non-randomised, first-in-man trial at 13 percutaneous coronary intervention centres in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. Eligible patients had stable or unstable angina or documented silent ischaemia, and a maximum of two de-novo lesions with a reference vessel diameter between 2·2 mm and 3·7 mm. Clinical follow-up was scheduled at months 1, 6, 12, 24, and 36. Patients were scheduled for angiographic follow-up at 6 months, and a subgroup of patients was scheduled for intravascular ultrasound, optical coherence tomography, and vasomotion assessment. All patients were recommended to take dual antiplatelet treatment for at least 6 months. The primary endpoint was in-segment late lumen loss at 6 months. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01960504.. Between Oct 8, 2013, and May 22, 2015, we enrolled 123 patients with 123 coronary target lesions. At 6 months, mean in-segment late lumen loss was 0·27 mm (SD 0·37), and angiographically discernable vasomotion was documented in 20 (80%) of 25 patients. Intravascular ultrasound assessments showed a preservation of the scaffold area (mean 6·24 mm(2) [SD 1·15] post-procedure vs 6·21 mm(2) [1·22] at 6 months) with a low mean neointimal area (0·08 mm(2) [0·09]), and optical coherence tomography did not detect any intraluminal mass. Target lesion failure occurred in four (3%) patients: one (<1%) patient died from cardiac death, one (<1%) patient had periprocedural myocardial infarction, and two (2%) patients needed clinically driven target lesion revascularisation. No definite or probable scaffold thrombosis was observed.. Our findings show that implantation of the DREAMS 2G device in de-novo coronary lesions is feasible, with favourable safety and performance outcomes at 6 months. This novel absorbable metal scaffold could be an alternative to absorbable polymeric scaffolds for treatment of obstructive coronary disease.. Biotronik AG.

Topics: Absorbable Implants; Aged; Alloys; Antibiotics, Antineoplastic; Cohort Studies; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Endosonography; Female; Humans; Magnesium; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome

Topics: Absorbable Implants; Coronary Restenosis; Drug-Eluting Stents; Humans; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

To compare the long-term clinical outcomes between Resolute zotarolimus-eluting stent (R-ZES) and paclitaxel-eluting stent (PES) in patients with small coronary artery disease.. Patients with a small vessel diameter are independently associated with increased risk of adverse cardiac events after drug-eluting stent implantation.. A cohort of 265 patients treated with R-ZES (185 patients with 211 lesions) or PES (80 patients with 100 lesions) in small vessel (≤2.5 mm) lesions were retrospectively analyzed. The primary end point of the study was the composite of major adverse cardiac events. The secondary end points included target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis at 3 years.. The baseline characteristics were similar between the 2 groups. In the R-ZES group, the mean stent diameter was smaller and the total stent length per lesion was longer. Major adverse cardiac events occurred in 8 (10%) patients who had received PES and in 7 (3.8%) patients who had received R-ZES (P = .07). The rates of 3-year TLR (2.2% vs 2.5%; P = 1.00) and TVR (5.4% vs 10.0%; P = .17) showed no statistically significant difference between the R-ZES and PES groups. The rate of stent thrombosis was 0.5% in the R-ZES group and 2.5% in the PES group (P = .21).. The rates of major adverse cardiac events and cardiac death were similar in the R-ZES-treated group compared with the PES-treated group.

Topics: Adult; Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Retrospective Studies; Risk Factors; Sirolimus; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Myocardial Infarction; Sirolimus; Treatment Outcome

Topics: Absorbable Implants; Antibiotics, Antineoplastic; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Sirolimus; Tissue Scaffolds

Topics: Coronary Restenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Myocardial Infarction; Sirolimus; Time Factors; Treatment Outcome

Topics: Absorbable Implants; Antigens, CD34; Cardiology; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Restenosis; Drug-Eluting Stents; Endothelial Progenitor Cells; Forecasting; Humans; Polymers; Sirolimus

Topics: Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Myocardial Infarction; Paclitaxel; Sirolimus; Stents; Time Factors; Treatment Outcome

Antiplatelet and antithrombotic therapies are systematically considered to prevent restenosis following coronary stent implantation. Currently, patients receiving medicated stents are prescribed to orally take anticoagulants and antiplatelet drugs such as aspirin (ASP) and prasugrel (PRAS). Propolis (PROP) known as a natural organic compound was recently evaluated for its antiplatelet activity, antibiotics and immunomodulatory activities. In this study, antiplatelet drug-coated Co-Cr substrates were prepared with biodegradable poly(d,l-lactide) (PDLLA) containing ASP, PRA, or PROP using electrospray and the blood compatibility of the different substrates was investigated by measuring protein adsorption and platelet adhesion. In addition, the anti-inflammatory properties of the modified Co-Cr surfaces were assessed by measuring IL-8 and IL-6 expression levels in human endothelial cell cultures. Drug-coated surfaces were found to resist the adsorption of fibrinogen when compared to bare Co-Cr or PDLLA-coated Co-Cr. Interestingly, ASP- and PROP-containing substrates not only showed reduced adhesion of platelets and delayed coagulation time, but also drastically reduced the expression level of IL-8 and IL-6. Such results are supported that ASP- or PROP-coated Co-Cr can be potentially used as a stent material to mitigate early stage of restenosis. The developed coating materials might be an interesting alternative to systemic anticoagulant therapies prescribed after stent implantation.

Topics: Anti-Inflammatory Agents; Aspirin; Cells, Cultured; Chromium Alloys; Cobalt; Coronary Restenosis; Drug Liberation; Drug Synergism; Drug-Eluting Stents; Humans; Microscopy, Electron, Scanning; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation Inhibitors; Polyesters; Prasugrel Hydrochloride; Propolis; Sirolimus

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Sirolimus

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Sirolimus

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Humans; Insulin Resistance; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Topics: Angioscopy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Sirolimus; Treatment Outcome

Topics: Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus; Stents; Treatment Outcome

The aim of this study was to evaluate antiproliferative sirolimus- and antioxidative alpha-lipoic acid (ALA)-eluting stents using biodegradable polymer [poly-L-lactic acid (PLA)] in a porcine coronary overstretch restenosis model. Forty coronary arteries of 20 pigs were randomized into four groups in which the coronary arteries had a bare metal stent (BMS, n = 10), ALA-eluting stent with PLA (AES, n = 10), sirolimus-eluting stent with PLA (SES, n = 10), or sirolimus- and ALA-eluting stent with PLA (SAS, n = 10). A histopathological analysis was performed 28 days after the stenting. The ALA and sirolimus released slowly over 30 days. There were no significant differences between groups in the injury or inflammation score; however, there were significant differences in the percent area of stenosis (56.2 ± 11.78% in BMS vs. 51.5 ± 12.20% in AES vs. 34.7 ± 7.23% in SES vs. 28.7 ± 7.30% in SAS, P < 0.0001) and fibrin score [1.0 (range 1.0-1.0) in BMS vs. 1.0 (range 1.0-1.0) in AES vs. 2.0 (range 2.0-2.0) in SES vs. 2.0 (range 2.0-2.0) in SAS, P < 0.0001] between the four groups. The percent area of stenosis based on micro-computed tomography corresponded with the restenosis rates based on histopathological stenosis in different proportions in the four groups (54.8 ± 7.88% in BMS vs. 50.4 ± 14.87% in AES vs. 34.5 ± 7.22% in SES vs. 28.9 ± 7.22% in SAS, P < 0.05). SAS showed a better neointimal inhibitory effect than BMS, AES, and SES at 1 month after stenting in a porcine coronary restenosis model. Therefore, SAS with PLA can be a useful drug combination for coronary stent coating to suppress neointimal hyperplasia.

Topics: Animals; Coronary Restenosis; Drug-Eluting Stents; Fibroblasts; Rats; Sirolimus; Swine; Thioctic Acid; Treatment Outcome

To evaluate angiographic and clinical results of ZES compared with EES after recanalization of CTOs.. ZES and EES showed similar clinical results in non-CTO lesions. Whether ZES and EES are also comparable in true CTO lesions (TIMI 0 flow, duration of occlusion of more than 3 months) with a higher risk of restenosis has not been addressed so far.. 125 patients with successful CTO recanalization via antegrade or retrograde approach were included. EES were implanted in 68 patients and ZES in 57 patients. Dual antiplatelet therapy was prescribed for 12 months. Follow-up angiography was scheduled at 9 months and clinical follow-up at 12 months. The primary angiographic outcome measure was in-stent late lumen loss. Primary clinical outcome measures were target lesion revascularization rate (TLR) and major adverse cardiac events (MACE) as a composite of cardiac death, TLR and myocardial infarction not clearly attributable to a non-target vessel.. Baseline characteristics were similar in both groups. Mean stent length was 72.8 ± 33.0mm with EES and 70.8 ± 31.5 mm with ZES (P = 0.72). In-stent late lumen loss was 0.50 ± 0.71 mm for EES compared with 0.59 ± 0.72 (P = 0.52) for ZES. There were similar rates for TLR (EES 10.3% versus ZES 10.5%, P = 0.97) and MACE (EES 10.3% versus ZES 12.3%). No definite or probable stent thrombosis occurred. Stent length but not type of stent was predictive for in-stent late loss and TLR.. ZES and EES showed similar angiographic and clinical outcomes for treatment of CTOs. © 2016 Wiley Periodicals, Inc.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Humans; Metals; Myocardial Infarction; Paclitaxel; Renal Dialysis; Sirolimus; Stents; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Metals; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Metals; Paclitaxel; Sirolimus; Stents

Little is known about the long-term outcomes after first-generation sirolimus-eluting stent (SES) implantation. We aimed to investigate the clinical outcomes up to 10 years after SES implantation.. The study population comprised 342 patients (504 lesions) who underwent SES implantation between January 2002 and December 2004. The median duration of follow-up was 3816 days (interquartile range [Q1-Q3], 3,705-3,883 days).. The cumulative event rate of definite stent thrombosis was 3.9%. The cumulative rate of target lesion revascularization (TLR) at 1, 5, and 10 years was 8.7%, 18.8%, and 31.1%, respectively, and the annual rate of TLR was 3.1%. Clinically driven TLR occurred at relatively constant rate during 10 years (2.0% per year). In a multivariate analysis, higher body mass index, hemodialysis, in-stent restenosis (ISR) target lesion, and total stent length >30 mm were independent risk factors of TLR within 5 years. An independent risk factor of TLR beyond 5 years was ISR target lesion.. Late TLR after SES implantation is a long-term hazard, lasting up to 10 years. The ISR target lesion is a risk factor of TLR during 10 years.

Topics: Aged; Aged, 80 and over; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Japan; Long Term Adverse Effects; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Registries; Retrospective Studies; Risk Factors; Sirolimus

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus; Stents; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Humans; Metals; Paclitaxel; Sirolimus; Stents; Treatment Outcome

We report a case of bioresorbable vascular scaffold restenosis which could be caused by abnormal resorption 17months after implantation.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Prosthesis Design; Retreatment; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Antiphospholipid Syndrome; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Middle Aged; Myocardial Infarction; Reoperation; Sirolimus; TOR Serine-Threonine Kinases; Treatment Outcome

Coronary arterial disease (CAD) remains the leading cause of death globally. Percutaneous coronary interventions are frequently used nonsurgical techniques for treating CAD, which may unfortunately lead to arterial restenosis. Currently, there are no effective drugs that can thoroughly prevent restenosis. We hypothesize inflammation-triggerable nanomedicines may function as effective therapeutics for targeted therapy of restenosis, by preferentially releasing their payload at the diseased site. To demonstrate our hypothesis and develop targeted nanotherapies for restenosis, this study was designed to examine effectiveness of nanomedicines responsive to the inflammatory microenvironment with mild acidity and high reactive oxygen species (ROS). To this end, an acetalated β-cyclodextrin (β-CD) material (Ac-bCD) was synthesized as a pH-responsive carrier material, while a ROS-responsive material (Ox-bCD) was produced by hydrophobic functionalization of β-CD with an oxidation-labile group. Based on these two responsive materials, either pH- or ROS-responsive nanoparticles (NPs) were produced by a nanoprecipitation technique and fully characterized. Using rapamycin (RAP) as a candidate drug, responsive nanotherapies were fabricated. In vitro hydrolysis and release studies confirmed these nanovehicles and nanotherapies exhibited desirable responsive behaviors. Both in vitro cell culture and in vivo evaluations revealed their good safety profile. These responsive NPs could be effectively internalized by rat vascular smooth muscle cells, which in turn notably potentiated anti-proliferation and anti-migration activities of RAP. After intravenous (i.v.) injection, NPs may be accumulated at the injured site in the carotid artery of rats subjected to balloon angioplasty injury. Compared with a non-responsive nanotherapy based on poly(lactide-co-glycolide), treatment with either pH- or ROS-responsive nanotherapy by i.v. injection more effectively attenuated neointimal hyperplasia in a rat model of arterial restenosis. Accordingly, nanotherapeutics responsive to the inflammatory microenvironment hold great potential for the management of vascular restenosis by selectively releasing drug molecules at the inflamed sites.

Topics: Animals; Arteritis; beta-Cyclodextrins; Cells, Cultured; Cellular Microenvironment; Coronary Restenosis; Immunosuppressive Agents; Male; Molecular Targeted Therapy; Nanocapsules; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sirolimus; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Sirolimus; Stents; Treatment Outcome

Stent delivery failure may occur especially when treating complex coronary artery stenosis. XLIMUS (CARDIONOVUM GmbH, Bonn, Germany) is a new sirolimus-eluting stent (SES) with the following features: 1) cobalt chromium stent platform, with low (73 μm) strut thickness, (2) biodegradable polymer, and 3) potent antiproliferative drug (Sirolimus). Preliminary data suggest that XLIMUS SES may be ideal for the treatment of complex lesions.. In this registry, we assessed the deliverability, safety, and efficacy of percutaneous coronary interventions (PCI) using the XLIMUS SES in patients undergoing elective PCI in native coronary vessels for complex de novo lesions, including severe calcification, severe tortuosity, and chronic total occlusion. The primary objective of the study is the delivery success of the XLIMUS SES. The secondary objective is the 1-year rate of major adverse cardiac events (MACE; including all-cause death, nonfatal myocardial infarction, and repeat revascularization).. A total of 200 consecutive patients with 255 lesions were included. Delivery success was obtained in 196 (98%) patients and in 251 (98.4%) lesions. The XLIMUS SES was successfully implanted on the first attempt with a single guidewire in 176 (88%) patients and in 208 (81.6%) lesions. Additional techniques to facilitate stent delivery (i.e., buddy wire, anchoring-balloon, or GuideLiner catheter) were necessary in 47 (18.4%) lesions. Failure in XLIMUS SES implantation occurred in 4 (1.6%) lesions. MACE rate at 1 year was 9%.. This registry supports the positive performance of the XLIMUS SES in the treatment of complex coronary artery lesions.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Registries; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

In-stent hyperplasia (ISH) may develop in regions of low endothelial shear stress (ESS), but the relationship between the magnitude of low ESS, the extent of ISH, and subsequent clinical events has not been investigated.. We assessed the association of poststent ESS with neointimal ISH and clinical outcomes in patients treated with percutaneous coronary interventions (PCI). Three-dimensional coronary reconstruction was performed in 374 post-PCI patients at baseline and 6 to 10 months follow-up as part of the PREDICTION Study. Each vessel was divided into 1.5-mm-long segments, and we calculated the local ESS within each stented segment at baseline. At follow-up, we assessed ISH and the occurrence of a clinically indicated repeat PCI for in-stent restenosis. In 246 total stents (54 overlapping), 100 (40.7%) were bare-metal stents (BMS), 104 (42.3%) sirolimus-eluting stents, and 42 (17.1%) paclitaxel-eluting stents. In BMS, low ESS post-PCI at baseline was independently associated with ISH (β=1.47 mm(2) per 1-Pa decrease; 95% CI, 0.38-2.56; P<0.01). ISH was minimal in drug-eluting stents. During follow-up, repeat PCI in BMS was performed in 21 stents (8.5%). There was no significant association between post-PCI ESS and in-stent restenosis requiring PCI.. Low ESS after BMS implantation is associated with subsequent ISH. ISH is strongly inhibited by drug-eluting stents. Post-PCI ESS is not associated with in-stent restenosis requiring repeat PCI. ESS is an important determinant of ISH in BMS, but ISH of large magnitude to require PCI for in-stent restenosis is likely attributed to factors other than ESS within the stent.

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Early Diagnosis; Female; Follow-Up Studies; Hemodynamics; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Stents; Stress, Mechanical; Treatment Outcome

At present no proven standard treatment for drug-eluting stent (DES) restenosis is available, and the efficacy and safety of everolimus-eluting stent (EES) and zotarolimus-eluting stent (ZES) for DES restenosis are limited. The purpose of this prospective, randomized 9-month intracoronary ultrasound (IVUS) and 3-year clinical follow-up study was to compare the effects of EESs and ZESs on neointima volume and major adverse cardiovascular events (MACEs) such as death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis in DES restenosis patients.. Patients with first- and second-generation DES restenosis, both EES and ZES implantation were effective and safe in reducing neointima volume and late loss with a comparable rate of MACEs independent of cardiovascular risk factors.

Topics: Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Treatment Outcome

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus; Stents; Treatment Outcome

Adhesion molecules play an important role in inflammation, atherosclerosis and coronary artery disease (CAD). These molecules are expressed on the surface of dysfunctional endothelial cells, causing inflammatory cells from the circulation to adhere and migrate through the endothelium. Their expression is upregulated in acute coronary syndrome (ACS) and after percutaneous coronary intervention (PCI). The contact between stent struts and endothelium upregulates endothelial cell gene expression, endothelial cell activation and inflammation. The paclitaxel or sirolimus eluting stents inhibited expression of adhesion molecules in several studies and reduced the incidence of major adverse cardiac events (MACE) after drug-eluting stent (DES) over bare metal stent (BMS) implantation. Therefore, we propose that elevated serum levels of the soluble adhesion molecules after primary PCI in patients treated with BMS or DES implantation versus drug-coated balloon (DCB) application to the vulnerable coronary plaque might be a predictor of MACE and further adverse outcomes. Consequently, DCB-only strategy in patients with ACS might be a superior approach in comparison to BMS implantation and non-inferior approach when compared to DES implantation.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Atherosclerosis; Cell Adhesion Molecules; Coronary Artery Disease; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Metals; P-Selectin; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus; Up-Regulation; Vascular Cell Adhesion Molecule-1

The unique physical properties of optical coherence tomography (OCT) make it a useful technique in the study of restenosis mechanisms. In fact, OCT is able to differentiate between neointimal proliferation and neoatherosclerosis within the stent. We report a rare case of occlusive neoatherosclerosis presenting beyond one year after a successful drug-eluting stent implantation. The impact of OCT findings in the clinical decision making process is emphasized.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Occlusion; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Hypolipidemic Agents; Male; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Retreatment; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

We assessed long-term outcomes in patients with extra-small (XS) (≤2.25 mm) and small vessels (SV) (>2.25-2.75 mm) treated with the Resolute zotarolimus-eluting stent (R-ZES).. Data from eight studies including patients with XS or SV were pooled for this analysis. Among 2,141 patients (837 XS, 1,304 SV), three-year cumulative major adverse cardiac events (15.4% vs. 11.5%; adj. HR [95% CI]: 1.3 [1.0, 1.7], p=0.12), target lesion failure (12.4% vs. 9.3%, adj. HR: 1.1 [0.8, 1.5], p=0.56), and target lesion revascularisation (TLR: 6.9% vs. 4.5%, adj. HR 1.4 [0.9, 2.1], p=0.17) were greater in the XS cohort but were not significantly different after propensity adjustment. Target vessel revascularisation occurred more frequently in XS patients in both unadjusted and adjusted analyses (11.2% vs. 7.6%, adj. HR: 1.5 [1.1, 2.1], p=0.02). Stent thrombosis was low in both cohorts (1.2% vs. 0.6%, p=0.09). In the XS cohort, insulin-dependent diabetics had over twofold higher rates of TLR than non-diabetics (13.6% vs. 6.0%, p=0.02).. Long-term lesion-specific results among patients with XS vessels treated with the R-ZES were not significantly different from those among patients with SV, but specific patients with XS vessels (e.g., insulin-dependent diabetics) may remain at high risk for TLR.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Sirolimus; Treatment Outcome

Novel sirolimus eluting stents (SES) have shown non-inferior clinical outcomes when compared to everolimus eluting stents (EES), however only limited preclinical data have been published. Therefore, we evaluate vascular response of a new generation biodegradable polymer SES (BP-SES: Alex Plus, Balton) and fluoropolymer EES (EES: Xience Pro, Abbott) in the porcine coronary restenosis model.. A total of 40 stents were implanted with 120% overstretch in coronaries of 17 domestic swine: 16 BP-SES, 16 EES and 8 bare metal controls (BMS). Following 28 and 90 days, coronary angiography and optical coherence tomography (OCT) was performed, animals sacrificed and stented segments harvested for pathological evaluation.. At 28 days neointimal thickness in OCT was lowest in the BP-SES when compared to EES and BMS (0.18 ± 0.1 vs. 0.39 ± 0.1 vs. 0.34 ± 0.2 mm, respectively; p = 0.04). There was no difference in the proportion of malapposed or uncovered struts, although protruding covered struts were more common in BP-SES (14.8 ± 10% vs. 4.1 ± 4% vs. 3.7 ± 6%; p = 0.03). In pathology, the lowest neointimal thickness was confirmed in BP-SES (p < 0.05). The inflammation score was significantly lower in BP-SES and EES when compared to BMS (0.24 ± 0.1 vs. 0.4 ± 0.1 vs. 0.77 ± 0.4; p < 0.01) whilst EES and BP-SES had higher fibrin scores than BMS (1.2 ± 0.4 vs. 1.3 ± 0.3 vs. 0.17 ± 0.2; p < 0.01). At 90 days neointimal coverage and thickness in OCT was comparable between groups and healing in histopathology was complete.. New generation, BP-SES show similar vascular healing and biocompatibility profile with marginally higher degree of restenosis inhibition, when compared to fluoropolymer EES in the porcine coronary restenosis model.

Topics: Absorbable Implants; Animals; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Everolimus; Female; Immunosuppressive Agents; Male; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Sirolimus; Swine; Tomography, Optical Coherence

A 78-year-old man with unstable angina showed 90% stenosis in the proximal left anterior descending artery. Pre-procedural intravascular ultrasound revealed ruptured plaque and attenuated plaque in the lesion. Under these conditions, two overlapping sirolimus-eluting stent (SES) implantation in this lesion resulted in slow flow which was recovered by intracoronary nitrates, nicorandil, and nitroprusside without further complications. When the patient showed up again 5 years later with recurrence of angina pectoris, angiography revealed a hazy ulcerated in-stent restenosis (ISR) at the site of the SES. Pre-procedural optical coherence tomography (OCT) imaging revealed multiple intimal ruptures, cavity formation behind the stent struts, a thin-cap fibroatheroma containing neointima surrounded by signal-poor, lipid-rich area in the proximal SES, suggesting the progression of neoatherosclerosis within SES. Importantly, there occurred slow flow again after balloon angioplasty for this lesion. We would suggest careful OCT examination is warranted to confirm development of neoatherosclerosis within the stent, and distal protection device should be considered to prevent slow flow phenomenon even in a patient with very late ISR.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Circulation; Coronary Restenosis; Coronary Stenosis; Denture, Partial, Temporary; Drug-Eluting Stents; Humans; Male; No-Reflow Phenomenon; Recurrence; Retreatment; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

We describe a case of very late stent thrombosis with documentation of highly calcific restenosis at optical coherence tomography without clear signs of stent malapposition, neoatherosclerosis disruption, or vascular toxicity to stent polymer. To the best of our knowledge, this is one of the first reports dealing with highly calcific restenosis as a potential background to very late stent thrombosis.

Topics: Calcinosis; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Humans; Male; Middle Aged; Myocardial Infarction; Sirolimus; Tomography, Optical Coherence

A 71-year-old man presented in emergency department for non-ST-elevation myocardial infarction. At admission, 12-lead ECG was in sinus rhythm without sign of myocardial ischemia, and troponin slightly increased. The only notable feature of the patient's medical history was single-vessel coronary artery disease revealed 10 years previously, treated by stenting of the second segment of the right coronary artery with a 3.0 x 25 mm bare metal stent. Three months later, intrastent restenosis was managed by implantation of a 3.0 × 28 mm paclitaxel-eluting stent. Two years before the present admission, following a non contributive stress test for atypical chest pain, coronary angiogram had found a 60% diffuse intrastent restenosis. The present coronary angiogram performed via a right transradial approach demonstrated a focal intrastent restenosis (85%) with irregular contours. Optical coherence tomography (OCT) showed an atherosclerotic intrastent neolesion with intimal tear. OCT demonstrated more precisely a minimal luminal area of 1.02 mm (77.9% area stenosis), two wide cavities (length 1.1 and 1.4 mm) separated by a plaque rupture of 6.8 mm. Myocardial ischemia was evenly demonstrated on this artery with a fractional flow reserve under 0.50 after 150 mg intracoronary adenosine bolus. The culprit lesion was treated by a 3.0 × 38 mm everolimus-eluting stent, with good angiographic results, confirmed on OCT.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Male; Myocardial Ischemia; Myocardial Revascularization; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Sirolimus; Tomography, Optical Coherence

We performed a propensity score-matching comparison of the midterm clinical and angiographic outcomes after primary stenting between using bare-metal stents (BMSs) and sirolimus-eluting stent (SES; Cypher Bx Velocity) for ST-segment elevated myocardial infarction (STEMI), because, in the drug-eluting stent era, the indication of the BMSs when a large balloon diameter is required remained to be controversial. This was a single-center, nonrandomized, retrospective study investigated in October 2013 by enrolling STEMI patients treated with primary stenting using either SES (n = 468) or BMS (n = 171) between September 2004 and December 2011. In 204 patients, the baseline-adjusted values produced similar mean maximum balloon sizes (BMS 3.67 ± 0.47 mm; SES 3.70 ± 0.56 mm; p = 0.477), and the incidence rates of binary in-stent restenosis (% diameter stenosis >50 % on secondary angiography) after SES placement (7.8 %) was significantly lower than that after BMS placement (23.5 %; p = 0.002). In baseline-adjusted 300 patients, the incidence of the clinical endpoints comprising cardiac death, nonfatal recurrent MI, and definite stent thrombosis after SES placement (11.3 %; 1241 ± 786 days; p = 0.557) was not significantly different from after BMS placement (8.7 %; mean follow-up period, 549 ± 486 days; p = 0.557). SES was not significantly related to the clinical endpoint [hazard ratio 2.31; 95 % confidence interval (CI) 0.88-6.08; p = 0.089). BMS did not offset the SES's angiographic efficacy for primary stenting for STEMI patients, despite placed using a large-sized balloon.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Metals; Middle Aged; Myocardial Infarction; Propensity Score; Retrospective Studies; Sirolimus; Stents; Treatment Outcome

This study evaluated the safety and efficacy of the RESOLUTE(TM)zotarolimus-eluting stent (R-ZES; Medtronic, Inc, Santa Rosa, CA, USA) in Japanese patients for the treatment of de novo native coronary lesions.. Both RESOLUTE Japan (R-Japan) and RESOLUTE Japan Small Vessel Study (R-Japan SVS) were prospective, multicenter, single-arm observational studies. R-Japan enrolled 100 patients (reference vessel diameter, 2.5-3.5 mm) and R-Japan SVS enrolled 65 patients (at least 1 lesion suitable for 2.25-mm stent) treated with R-ZES. In R-Japan, in-stent late lumen loss (LLL; the primary endpoint) at 8 months was 0.12 ± 0.22 mm and volume obstruction on intravascular ultrasound was 2.33 ± 3.51%. At 4 years, there were no cases of clinically driven target lesion revascularization (TLR); the target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, and clinically driven TLR) was 5.6% (5/90). In R-Japan SVS, in-stent LLL at 9 months was 0.27 ± 0.33 mm, TLF (primary endpoint) was 4.6% (3/65), without incidence of TLR. At 3 years, TLF was 7.9% (5/63) and clinically driven TLR, 3.2% (2/63).. R-Japan and R-Japan SVS demonstrate substantial suppression of neointimal hyperplasia, low LLL, and excellent and sustained long-term clinical outcome with R-ZES in Japanese patients.

Topics: Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Heart Diseases; Humans; Incidence; Japan; Myocardial Infarction; Myocardial Revascularization; Neointima; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Risk Factors; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

The angiographic features of restenosis contain prognostic information. However, restenosis patterns of the new generation drug-eluting stents (DES), everolimus-(EES) and resolute zotarolimus-eluting stent (ZES) have not been described.A total of 210 consecutive patients with DES restenosis were enrolled from 2003 to 2012. We analyzed 217 restenotic lesions after DES implantation, and compared the morphologic characteristics of the 2nd generation DES restenosis to those of restenosis with 2 first generation DES, sirolimus-(SES) and paclitaxel-eluting stent (PES).Baseline characteristics were comparable between the different stent groups. The incidence of focal restenosis was significantly lower for PES than the other stents (49.5% versus 87.0%, 76.2%, and 82.1% for PES versus SES, EES, and ZES, respectively, P < 0.001). When considering the pattern of restenosis solely within the stent margins, a further clear distinction between PES and other stents was observed (40.0% versus 92.9%, 88.9%, and 81.2% in PES versus SES, EES, and ZES, respectively, P < 0.001). There were no significant differences in restenosis patterns among SES, EES, and ZES. In multivariate analysis, PES implantation, hypertension, and age were associated with non-focal type of restenosis after DES implantation. After the introduction of EES and ZES into routine clinical practice in 2008, focal restenosis significantly increased from 63.9% to 76.7% and diffuse restenosis significantly decreased from 26.4% to 11.0% (P = 0.045).Focal restenosis was the most common pattern of restenosis in the new generation DES and the incidence of diffuse restenosis significantly decreased with the introduction of the 2nd generation DES.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Postoperative Complications; Registries; Republic of Korea; Sirolimus; Treatment Outcome; Vascular Patency

Although paclitaxel-coated balloon (PCB) angioplasty has been reported to be effective for in-stent restenosis (ISR) lesions, the optimal treatment for recurrent ISR lesions caused by PCB failure remains unclear. This study compared clinical and angiographic outcomes after everolimus-eluting stent (EES) implantation and repeat PCB angioplasty for PCB failure.. From November 2008 to October 2011, we performed PCB angioplasty for 599 ISR lesions, of which 93 recurrent ISR lesions underwent EES implantation (53 lesions, 52 patients) or repeat PCB angioplasty (40 lesions, 37 patients). The choice of treatment strategy was decided at the operatorÕs discretion. Angiographic outcomes were evaluated by follow-up angiography at six to eight months after procedure. The baseline characteristics were similar between the two groups. At follow-up angiography (93.5% of all lesions), minimum lumen diameter was significantly larger and the binary restenosis rate was significantly lower after EES implantation than after repeat PCB angioplasty (2.08±0.79 mm vs. 1.45±0.68 mm, p<0.001; 20.0% vs. 54.1%, p=0.001; respectively), whereas late lumen loss was not different between the two groups (0.49±0.62 mm vs. 0.59±0.74 mm, p=0.47). At two years, the incidences of both target lesion revascularisation (TLR) and clinically driven TLR were significantly lower after EES implantation than after repeat PCB angioplasty (17.9% vs. 57.5%, p=0.001; 5.9% vs. 18.1%, p=0.01; respectively).. EES implantation was more effective for PCB failure in preventing subsequent TLR than repeat PCB angioplasty because of better angiographic results.

Topics: Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Paclitaxel; Prosthesis Design; Recurrence; Sirolimus; Treatment Outcome

We conducted a lesion-based retrospective sub-analyses of diabetes mellitus (DM), diffuse long lesions (stented segment ≥40 mm; LLs), and small vessels (SVs; reference diameter ≤2.6 mm) in patients who received sirolimus- (SESs) or paclitaxel-eluting stents (PESs) for nonrandom treatment of de novo native coronary stenosis in a clinical practice setting. During the period from May 2007 to February 2009, 490 of 682 PES-treated and 293 of 386 SES-treated lesions were angiographically followed up within 1500 days of PCI, and the retrospective investigation was conducted in April 2013. The frequencies of target lesion revascularization (TLR; any recurrent PCI including both marginal stent restenosis) and binary in-stent restenosis (percentage diameter of in-stent stenosis >50%) upon follow-up angiography, evaluated by adjusting 25 baseline variables using propensity score matching analysis, after placement of SESs and PESs were the following: DM (n = 124 per arm), 14.5 vs. 15.3% (p = 0.842), and 14.5 vs. 16.1% (0.856); LLs (n = 81), 16.0 vs. 21.0% (0.433), and 12.3 vs. 22.2% (0.117); SVs (n = 107), 11.2 vs. 29.9% (<0.001), and 11.2 vs. 30.8% (<0.001), respectively. The p values of log-rank tests for the cumulative TLR-free ratios after SES and PES placement were 0.504 in DM, 0.625 in LLs, and <0.001 in SVs group, respectively. Thus, compared to PES, SES showed the equivalent efficacy for DM, the tendency to be superior for LLs due to approximately 24-45% reductions in TLR and binary restenosis rates, and the promising superiority for SVs on the angiographic outcomes during a long-term observational interval.

Topics: Aged; Antineoplastic Agents, Phytogenic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Paclitaxel; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

The aim was to assess the effectiveness and safety profile of a new dedicated bifurcation stent - sirolimus-eluting BiOSS LIM® (Balton, Poland) in 12-month Registry.. The optimal approach to coronary bifurcations treatment by percutaneous coronary intervention (PCI) has been still a subject of debate. Dedicated bifurcation stents are one of the proposed solutions.. This was the international, 3-center registry, which enrolled patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and stable angina. Provisional T-stenting was the obligatory strategy of the treatment. Angiographic control was planned at 12 months. The primary endpoint was cumulative rate of death, myocardial infarction (MI) and target lesion revascularization (TLR) at 12 months.. A total of 60 patients with coronary bifurcations were enrolled (mean age 66.4 ± 11 years, 28.3% of female). There were 21.7% of patients with NSTE-ACS, 78.3% with hypertension, 38.3% with diabetes, 28.3% had previous MI, and 46.7% and 10% underwent prior revascularization, respectively, PCI and coronary artery bypass graft. The device success rate was 100%. Side branch was treated with an additional classical drug-eluting stent implantation in 23.3% of cases. At 12 months, the cumulative major adverse cardiovascular events rate was 11.7%. During follow-up (11 ± 1 months) there was 1 non-cardiac death (1.7%), 1 non-ST-elevated myocardial infarction (1.7%) due to restenosis and no case of stroke or in-stent thrombosis. Overall TLR was 8.3% (clinically driven TLR - 1.7%, angiographically driven - 6.6%). Mean late lumen loss was as follows: In main vessel - 0.35 ± 0.33 mm, in main branch - 0.34 ± 0.27 mm and in side branch - 0.18 ± 0.38 mm.. Dedicated bifurcation stent BiOSS® LIM proved to be feasible device, with promising safety and long-term clinical effectiveness in the treatment of coronary bifurcation lesions, including distal left main stem stenosis.

Topics: Acute Coronary Syndrome; Aged; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Europe; Female; Follow-Up Studies; Humans; Male; Prosthesis Design; Registries; Sirolimus

Topics: Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Percutaneous Coronary Intervention; Postoperative Complications; Sirolimus

Topics: Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Postoperative Complications; Sirolimus; Ticlopidine

Results of trials and registry studies have shown lower long-term mortality after coronary-artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI) among patients with multivessel disease. These previous analyses did not evaluate PCI with second-generation drug-eluting stents.. In an observational registry study, we compared the outcomes in patients with multivessel disease who underwent CABG with the outcomes in those who underwent PCI with the use of everolimus-eluting stents. The primary outcome was all-cause mortality. Secondary outcomes were the rates of myocardial infarction, stroke, and repeat revascularization. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics.. Among 34,819 eligible patients, 9223 patients who underwent PCI with everolimus-eluting stents and 9223 who underwent CABG had similar propensity scores and were included in the analyses. At a mean follow-up of 2.9 years, PCI with everolimus-eluting stents, as compared with CABG, was associated with a similar risk of death (3.1% per year and 2.9% per year, respectively; hazard ratio, 1.04; 95% confidence interval [CI], 0.93 to 1.17; P=0.50), higher risks of myocardial infarction (1.9% per year vs. 1.1% per year; hazard ratio, 1.51; 95% CI, 1.29 to 1.77; P<0.001) and repeat revascularization (7.2% per year vs. 3.1% per year; hazard ratio, 2.35; 95% CI, 2.14 to 2.58; P<0.001), and a lower risk of stroke (0.7% per year vs. 1.0% per year; hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). The higher risk of myocardial infarction with PCI than with CABG was not significant among patients with complete revascularization but was significant among those with incomplete revascularization (P=0.02 for interaction).. In a contemporary clinical-practice registry study, the risk of death associated with PCI with everolimus-eluting stents was similar to that associated with CABG. PCI was associated with a higher risk of myocardial infarction (among patients with incomplete revascularization) and repeat revascularization but a lower risk of stroke. (Funded by Abbott Vascular.).

Topics: Aged; Coronary Artery Bypass; Coronary Artery Disease; Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Complications; Propensity Score; Registries; Sirolimus; Stroke

The aim of this study was to compare the safety and efficacy of everolimus-eluting stent (EES), sirolimus-eluting stent (SES), and plain old balloon angioplasty (POBA) for the treatment of SES in-stent restenosis (S-ISR).. The optimal treatment for drug-eluting in-stent restenosis remains controversial.. The study cohort comprised 310 consecutive patients (444 lesions) who presented with S-ISR to our institution and underwent treatment with EES (43 patients), SES (102), or POBA (165). The analyzed clinical parameters were the 1-year rates of death, Q-wave myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), definite stent thrombosis (ST) and major adverse cardiac event (MACE) defined as the composite of death, MI, or TLR at 1-year.. The three groups were well matched for the conventional risk factors for coronary artery disease except for smoking. The 1-year analyzed clinical parameters were similar in the three groups: MACE (EES=14%, SES=18%, POBA=20%; p=0.65), death (EES=2.3%, SES=6.2%, POBA=6.1%; p=0.61), MI (EES=4.8%, SES=2.1%, POBA=2.5%; p=0.69), TLR (EES=11.9%, SES=12.1%, POBA=24%; p=0.78), and TVR (EES=11.9%, SES=24.8%, POBA=22.2%; p=0.23). There were no cases of definite ST. MACE-free rate was significantly lower in patients with recurrent in-stent restenosis (log-rank p=0.006). Presentation with acute MI, number of treated lesions and a previous history of MI were found to be independent predictors of MACE.. In patients presenting with S-ISR, treatment with implantation of an EES, SES, or POBA is associated with similar clinical outcomes. Patients presenting with recurrent ISR may have a poorer clinical outcome.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Confidence Intervals; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Patient Safety; Proportional Hazards Models; Retreatment; Retrospective Studies; Risk Assessment; Sirolimus; Statistics, Nonparametric; Survival Rate; Time Factors; Treatment Outcome

Topics: Adult; Coronary Restenosis; Drug-Eluting Stents; Humans; Male; Sirolimus

Fast releasing, rapamycin-eluting stents, although safe, showed inferior results with regard to inhibition of restenosis.. Therefore, we report vascular effects of a novel, biodegradable polymer stent matrix with elevated sirolimus dose and fast release kinetics (ed-frSES, Alex, Balton) in the porcine coronary in-stent restenosis model.. A total of 19 stents were implanted with 120% overstretch in the coronary arteries of seven domestic pigs: seven ed-frSES with 1.3 μg/mm2 of sirolimus, eight frSES with 1 μg/mm2 of sirolimus, and eight bare metal stents (BMS). For the following 28 days, coronary angiography was performed, animals were sacrificed, and the stented segments harvested for histopathological evaluation.. In angiography at 28 days the late lumen loss was lowest in the elevated dose sirolimus eluting stent (SES) (ed-frSES: 0.20 ± 0.2 vs. frSES: 0.80 ± 0.5 vs. BMS: 0.96 ± 0.5 mm, p < 0.01). This was confirmed in the morphometric evaluation in histopathology as represented by a significant and dose-dependent decrease in the percentage area of stenosis (ed-frSES: 22.4 ± 12.7% vs. frSES: 35 ± 10.7% vs. BMS: 47.5 ± 12.5%, p < 0.01). There was no peri-strut inflammation in any of the groups. However, the endothelialisation score was numerically not meaningfully decreased in ed-frSES (ed-frSES: 2.93 vs. frSES: 3. vs. BMS: 3, p = 0.05). Signs of fibrin were also noted in ed-frSES (ed-frSES: 0.4 vs. frSES: 0 vs. BMS: 0, p = 0.05).. Sirolimus dose-dependent vascular response was reported. The elevated dose, fast releasing SES shows satisfactory vascular healing, similar to regular dose, fast release SES, with improved efficacy in restenosis inhibition.

Topics: Absorbable Implants; Animals; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Inflammation; Models, Animal; Sirolimus; Swine

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Prosthesis Failure; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

As it is controversial whether metabolic syndrome (MetS) affects cardiovascular outcomes in patients who underwent percutaneous coronary intervention (PCI), we investigated the impact of MetS on clinical outcomes in patients who underwent PCI with everolimus-eluting stents (EESs). Patients who underwent PCI with EESs from 2009 to 2013 were included in this single-center, prospective cohort study. A composite event consisted of repeat revascularization, nonfatal myocardial infarction, and cardiac death. Of 903 patients observed for 4.9 years (median 1.8 years), 570 were diagnosed with MetS. The MetS group displayed more severe coronary artery disease and underwent more extensive PCIs than did the non-MetS group. The overall composite event rate was not significantly different between the MetS and the non-MetS group (11.9% vs 13.2%, p = 0.572). Kaplan-Meier survival analysis showed no significant difference in the event-free survival of the composite event between the 2 groups (p = 0.700). A multivariable Cox regression analysis showed that MetS was not associated with the composite event, whereas total stent length, decreased renal function, diabetes, and the absence of abdominal obesity were associated with the composite event. Abdominal obesity was associated with decreased risk of the composite event, alleviating unfavorable clinical outcomes of patients with diabetes in the MetS group. In conclusion, MetS has no impact on the clinical outcomes of patients who underwent PCI with EESs, although the MetS group exhibited more severe coronary artery disease and underwent more extensive PCIs. The paradoxical association between obesity and favorable clinical outcomes may explain this result.

Topics: Antineoplastic Agents; Coronary Angiography; Coronary Restenosis; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Metabolic Syndrome; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Period; Prognosis; Prospective Studies; Republic of Korea; Risk Assessment; Risk Factors; Sirolimus; Survival Rate; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Sirolimus

Topics: Acute Coronary Syndrome; Angioplasty; Coronary Restenosis; Drug-Eluting Stents; Humans; Male; Middle Aged; Myocytes, Smooth Muscle; Platelet Aggregation Inhibitors; Polytetrafluoroethylene; Sirolimus; Tomography, Optical Coherence

Second-generation drug-eluting stents (DES) have been used widely to treat DES in-stent restenosis (ISR), which remains a clinical challenge. Knowledge of the outcomes of repeated second-generation DES implantation for focal versus nonfocal-type ISR is still missing.. In the current study, 254 patients with DES-ISR were divided into focal or nonfocal groups according to their ISR angiographic types. All patients with ISR lesions included in the current study received second-generation DES. Treatment modalities for both groups were similar without any systematic bias toward either group. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACEs) over a 2-year follow-up period. MACEs were defined as cardiac death, myocardial infarction, and target lesion revascularization.. The nonfocal-type group showed significantly greater incidence of MACEs than the focal-type group (38.3 vs. 24.1%; P=0.03), in which the occurrence of target lesion revascularization was more pronounced (32.3 vs. 18.4%; P=0.02). However, this group showed a higher incidence of type B2/C lesions (69.5 vs. 41.4%; P<0.01), with longer lesion length, and received significantly more and longer reimplanted stents than the focal-type group. Cox regression analysis indicated that nonfocal-type ISR was an independent predictor of MACEs (odds ratio 2.134, 95% confidence interval 1.173-3.884; P=0.014) after adjusting for all significant variables.. In the current study, second-generation DES is more effective in the treatment of focal-type DES-ISR than nonfocal-type ISR in terms of the occurrence of MACEs. Nonfocal-type ISR is an independent predictor of MACEs after the treatment of DES-ISR with second-generation DES.

Topics: Aged; Antineoplastic Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Proportional Hazards Models; Retreatment; Retrospective Studies; Sirolimus; Treatment Outcome

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Guidelines as Topic; Hospitalization; Humans; Male; Myocardial Infarction; Sirolimus; Tomography, Optical Coherence

Initial preclinical studies are required during the process of improving polymers, platforms, and drug-eluting systems for new coronary stent designs. Our objective was to analyze the efficacy and safety of new drug-eluting stent models compared with a conventional stent and commercialized drug-eluting stents in an experimental model with healthy porcine coronary arteries.. Sixty stents (conventional stent, new sirolimus-eluting stents: drug-eluting stents 1, 2 and 3; Cypher(®) and Xience(®)) were randomly placed in the coronary arteries of 20 Large White domestic pigs. Angiographic and histomorphometric studies were done 28 days later.. The stents were implanted at a stent/artery ratio of 1.34±0.15, with no significant differences between groups. The new stents showed less late loss and angiographic restenosis than conventional stents (P=.006 and P<.001, respectively). Histologically, restenosis and neointimal area were lower with all the new platforms than with the conventional stents (P<.001 for each variable), and no differences were found vs the drug-eluting stents on the market. Safety data showed that endothelialization was lower with drug-eluting stents than with conventional stents, except for drug-eluting stent 3 (P=.084). Likewise, inflammation was lower with drug-eluting stent 3 than with other stents.. The new drug-eluting stent platforms studied are associated with less restenosis than conventional stents and showed no significant differences in safety or efficacy vs commercialized drug-eluting stents.

Topics: Animals; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Immunosuppressive Agents; Prosthesis Design; Random Allocation; Sirolimus; Sus scrofa; Swine

Stent fracture (SF) after sirolimus-eluting stent implantation is reported to be associated with target lesion revascularization (TLR) and stent thrombosis. We aimed to assess the clinical impact of SF at 8 years.. Between 2002 and 2005, 972 patients (1795 lesions) underwent sirolimus-eluting stent implantation and follow-up angiography within 1 year after index procedure. SF, defined as the complete separation of stent segments or stent struts at follow-up angiography, was observed in 105 lesions (5.8%). The study sample comprised 954 patients (1630 lesions), excluding 147 lesions undergoing TLR and 18 patients (18 lesions) who died or in whom stent thrombosis developed within 1 year after sirolimus-eluting stent implantation. The median follow-up duration was 9.1 years (the first and third quarters, 8.7 and 9.4 years). The primary end point was defined as any TLR. The 8-year cumulative rates of adverse events were estimated by Kaplan-Meier methods with P values from log-rank tests. Between patients with and without SF, there were no significant differences in the cumulative rates of all-cause death (23.5% versus 27.6%, P=0.35) and cardiac death (4.7% versus 9.1%, P=0.14), whereas patients with SF had significantly higher cumulative rates in myocardial infarction (10.1% versus 3.3%, P=0.001), very late stent thrombosis (6.8% versus 0.7%, P<0.001), any TLR (38.1% versus 10.8%, P<0.001), and clinically driven TLR (26.2% versus 6.6%, P<0.001).. SF after sirolimus-eluting stent implantation was consistently associated with higher rates of adverse cardiac events during the 8-year follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Prosthesis Failure; Sirolimus; Treatment Outcome

Topics: Angioplasty, Balloon; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Topics: Acute Coronary Syndrome; Aged; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Prosthesis Design; Sirolimus; Tomography, Optical Coherence

The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p <0.001). Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS.

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Metals; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The drug-eluting stent still has limitations such as thrombosis and inflammation. These limitations often occur in the absence of endothelialization. This study investigated the effects of WKYMVm- and sirolimus-coated stents on re-endothelialization and anti-restenosis. The WKYMVm peptide, specially synthesized for homing endothelial colony-forming cells, was coated onto a bare-metal stent with hyaluronic acid through a simple dip-coating method (designated HA-Pep). Thereafter, sirolimus was consecutively coated to onto the HA-Pep (designated Pep/SRL). The cellular response to stents by human umbilical-vein endothelial cells and vascular smooth-muscle cells was examined by XTT assay. Stents were implanted into rabbit iliac arteries, isolated 6 weeks post-implantation, and then subjected to histological analysis. The peptide was well attached to the surface of the stents and the sirolimus coating made the surface smooth. The release pattern for sirolimus was similar to that of commercial sirolimus-coated stents (57.2% within 7 days, with further release for up to 28 days). Endothelial-cell proliferation was enhanced in the HA-Pep group after 7 days of culture (38.2 ± 7.62%, compared with controls). On the other hand, the proliferation of smooth-muscle cells was inhibited in the Pep/SRL group after 7 days of culture (40.7 ± 6.71%, compared with controls). In an animal study, the restenosis rates for the Pep/SRL group (13.5 ± 4.50%) and commercial drug-eluting stents (Xience Prime™; 9.2 ± 7.20%) were lower than those for bare-metal stents (25.2 ± 4.52%) and HA-Pep stents (26.9 ± 3.88%). CD31 staining was incomplete for the bare-metal and Xience Prime™ groups. On the other hand, CD31 staining showed a consecutive linear pattern in the HA-Pep and Pep/SRL groups, suggesting that WKYMVm promotes endothelialization. These results indicate that the WKYMVm coating could promote endothelial healing, and consecutive coatings of WKYMVm and sirolimus onto bare-metal stents have a potential role in re-endothelialization and neointimal suppression.

Topics: Animals; Biocompatible Materials; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Drug-Eluting Stents; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Iliac Artery; Male; Materials Testing; Myocytes, Smooth Muscle; Neointima; Oligopeptides; Rabbits; Rats; Sirolimus

We evaluated and compared the incidence and characteristics of late catch-up phenomenon (LCU) between everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) implantations.. Late catch-up phenomenon after everolimus-eluting stent (EES) implantation has not yet been evaluated sufficiently.. Between April 2007 and May 2011, 1,234 patients with coronary artery disease were treated with SES and 502 patients with EES. Following propensity score matching, we evaluated 495 SES-treated patients and 495 ESS-treated patients. The incidences of LCU (i.e., late target lesion revascularization [TLR] [1-3 years]) were compared.. The cumulative incidence of TLR at 3 years was 11.9% in the SES group and 6.1% in the EES group (P = 0.001). The incidence of late TLR was 7.5% in the SES group and 3.4% in the EES group (P = 0.004). Even though not statistically significant, intravascular ultrasound showed a higher tendency of stent fracture (SF) in late restenosis lesions in the SES group than in the EES group (37.0% vs 7.7%; P = 0.052). Moreover, the SF rate tended to increase in late restenosis compared with early restenosis (within 1 year) in the SES group compared with the EES group (SES: 37.0% vs 22.2%; P = 0.293, EES: 7.7% vs 10.0%; P = 0.846), although the increase was not significantly different.. EES was superior to SES in terms of LCU. SF may be associated with LCU after SES implantation.

Topics: Aged; Aged, 80 and over; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Propensity Score; Sirolimus; Treatment Outcome

Topics: Absorbable Implants; Coronary Restenosis; Drug-Eluting Stents; Humans; Sirolimus; Treatment Outcome

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Delayed Diagnosis; Diagnosis, Differential; Drug-Eluting Stents; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Postoperative Complications; Sirolimus; Tomography, Optical Coherence; Ultrasonography, Interventional

In recent years, expanded data have demonstrated the association between increased inflammatory markers and risk of adverse cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) with stent implantation. Particularly, several studies have demonstrated association between increased C-reactive protein (CRP) level and various risk factors of cardiovascular diseases and their complications. The role of CRP in predicting restenosis after implantation of bare metal stents has been proven, but its role in predicting drug-eluting stents restenosis is still unproved. Significant association between increased white blood cells count and risk of development and severity of coronary artery disease and as well as poor prognosis after PCI has also been demonstrated. But erythrocyte sedimentation rate has been studied insufficiently in this regard. According to some studies, including those conducted in our institute, one can suggest an association between eosinophilic inflammatory response, progression of coronary atherosclerosis, and drug-eluting stents restenosis. Identification of factors affecting prognosis of patients with coronary heart disease after PCI will allow determining further strategy of patient management.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Humans; Prognosis; Sirolimus; Stents; Treatment Outcome

The role of the second-generation zotarolimus-eluting stent RESOLUTE in small-vessel coronary artery disease is unclear. The aim of this study was examine the angiographic results of RESOLUTE in de novo coronary lesions of ≥50 % diameter stenosis in target vessels ≤2.5 mm. From August 2008 to April 2010, 142 symptomatic patients with 159 lesions who fitted the inclusion criteria were treated with RESOLUTE. The mean age of patients was 66 ± 10 years, with male predominance (66 %). Diabetes mellitus was found in 62 (43.7 %) patients, whereas multivessel disease was observed in 105 (73.9 %). The mean stent size and length used were 2.33 ± 0.13 and 22 ± 8 mm, respectively. Follow-up angiography was performed on 143 (89.9 %) lesions in 127 (89.4 %) patients at a mean of 10.3 ± 3.6 months. Angiographic restenosis was found in 9 (6.3 %) lesions; the late loss was 0.26 ± 0.34 mm. At 1-year follow-up there were four cardiovascular deaths, two nonfatal myocardial infarctions, and six repeated revascularizations. The resultant major adverse cardiac event rate was 8.5 %. The use of RESOLUTE to treat small-vessel disease is associated with good clinical and angiographic outcomes at 1 year.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

A 60-year-old man who had received repeated angioplasty for silent ischemia was suspected to have restenosis based on radioisotope imaging (exercise-RI) findings 6 months after everolimus-eluting stent (EES) implantation (3.5 × 28, 3.5 × 28, 3.0 × 18 mm). The stents had been implanted for chronic total occlusion of the right coronary artery (RCA), and the patient was on continuous dual antiplatelet therapy. Diagnostic angiography demonstrated in-stent restenosis in the proximal RCA, which was treated by optical coherence tomography (OCT)-guided cutting balloon angioplasty with distal protection. OCT findings of the stenotic segment before angioplasty showed that the lesion had complex features. The lesion was successfully dilated, and whitish material obtained by a distal protection device was composed of fibrin thrombi with neutrophils and small pieces of mature fibrocellular neointima. The mechanisms and patterns of restenosis after EES placement have not been well clarified. This case may reflect a restenosis pattern (i.e., asymptomatic, focal, and thrombi-related) in the era of the newer generation of drug-eluting stents.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prosthesis Design; Severity of Illness Index; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Drug-eluting stent (DES) implantation is a very effective treatment of bare-metal stent-in-stent restenosis (BMS-ISR). Therapeutic options for drug-eluting stent-in-stent restenosis (DES-ISR) are less well defined, as there are only few data on safety and effectiveness of interventional modalities. This study compared the 1-year clinical outcome after the use of drug-eluting balloon (DEB) to second-generation everolimus-eluting stent (EES) for treatment of DES-ISR.. This observational study included 86 patients with 86 DES-ISR. Forty patients were treated by repeat percutaneous coronary intervention (PCI) using an EES. Forty-six patients were treated by repeat PCI using a DEB. Follow-up periods were 22 ± 11 and 25 ± 19 months, respectively. The primary endpoint of the study was survival free of major adverse cardiac events (MACEs) at 1 year. Secondary endpoints were needed for target lesion revascularization (TLR), definite stent thrombosis (ST) at 1 year, and MACE rate during total follow-up period.. Baseline clinical and angiographic parameters were comparable between the two groups. EES were associated with a higher MACE rate at 1 year compared to DEB (27.5 vs. 8.6%, respectively; P = 0.046). TLR rates for EES and DEB were 22.5% versus 4.3%, respectively, P = 0.029, while rates of definite ST at 1 year follow-up were comparable (2.5% vs. 0%, respectively; P = 0.945). There were no differences in myocardial infarction rates between the two groups (5% vs. 2%, respectively; P = 0.595) and in mortality. Considering the complete follow-up periods, DEB were associated with significantly less MACE compared to EES (log-rank test, P = 0.045). Furthermore, comparison of TLR rates showed a strong trend in favor of DEB compared to EES (P = 0.074).. Treatment of DES-ISR using a DEB is associated with favorable rates of MACE and TLR at 1-year follow-up compared to the implantation of an EES.

Topics: Aged; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Compared with the bare metal stent (BMS), suppression of neointimal growth in the sirolimus-eluting stent (SES) reduced restenosis at the cost of more exposed struts that could impose the risk of stent thrombosis. The present study was conducted to analyze neointimal coverage patterns of stents at a strut-level after implantation of BMS or SES with the use of optical coherence tomography (OCT). We enrolled 35 patients and analyzed neointimal coverage of every strut from 41 stents (BMS: n = 8, SES: n = 33) by using OCT at follow-up of the stent implantation. All of the 371 struts from eight BMSs were covered with ≥100 μm of neointima, while 19.8 and 3.5% of 3,478 struts from 33 SESs were uncovered (neointimal thickness of <10 μm) and malapposed, respectively. The histogram of neointimal thickness showed basically normal distribution in BMS but skewed in SES. No regional difference in neointimal thickness was observed in BMS (proximal, 535.7 ± 25.2 μm; body, 532.4 ± 17.0 μm; distal, 485.8 ± 27.0 μm). In SES, however, the body segment showed thinner neointima [median 40 μm (interquartile range (IQR) 10-90 μm)] than proximal [60 μm (IQR 10-140 μm), p < 0.001] or distal [50 μm (IQR 10-110 μm), p < 0.001] segment, while uncovered and malapposed struts were more frequent in the proximal and body segments. In conclusion, SES, compared with BMS, showed more suppressed neointimal growth with regional variation: neointimal thickness was the least in the body part while the ratio of exposed and malapposed struts was minimal in the distal segment. OCT was useful for a strut-level analysis of neointimal coverage over the whole stent.

Topics: Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Metals; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Few data exist with regard to the polymer integrity of drug-eluting stents (DES) in vivo. This study aims to investigate the integrity of the polymer layer of 4 polymer-coated DES in vivo. We assessed the morphology of the polymer layer of sirolimus-eluting stent (SES; Cypher Select™), paclitaxel-eluting stent (PES; Taxus Liberté™), zotarolimus-eluting stent (ZES; Endeavour RX™) and everolimus-eluting stent (EES; Xience V™) by scanning electron microscopy after balloon expansion at nominal and high pressures in the coronary arteries of 3 pigs. Effects of kissing balloon procedure were also explored. The polymer layer of SES, PES and EES were damaged in less than 3 % of the surface area with high pressure procedures, whereas the damaged area reached 38.0 ± 2.6 % in ZES (P < 0.01). The polymer integrity differed greatly among DES after balloon inflation in vivo. This should be taken into account when placing DES in tortuous vessels, calcified, as well as bifurcation lesions because the polymer layer may be easily damaged in these lesions.

Topics: Animals; Antineoplastic Agents, Phytogenic; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Restenosis; Disease Models, Animal; Drug-Eluting Stents; Everolimus; Immunosuppressive Agents; Paclitaxel; Prosthesis Design; Sirolimus; Swine

A 67-year-old man with recent myocardial infarction underwent a total of five sirolimus-eluting stents (SES) implantation for three vessels stage by stage. A follow-up angiography showed no significant restenosis except one in the side branch. Thereafter, he had remained asymptomatic. Sixty-six months later, he had an acute myocardial infarction with cardiogenic shock due to simultaneous 3-vessel very late stent thrombosis (VLST). After successful percutaneous coronary intervention, final angiography revealed serious peri-stent contrast staining along with positive remodeling and grade V stent fracture. This rare case illustrates simultaneous 3-vessel VLST, associating with multiple SES-related problems, under continuation of aspirin and cilostazol.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Radiography; Recurrence; Shock, Cardiogenic; Sirolimus; Time Factors; Treatment Outcome

Long-term clinical and angiographic outcomes after sirolimus (SES: Cypher Bx Velocity) and paclitaxel (PES: TAXUS Express)-eluting stent implantation were firstly compared in Japan. During PES-available period from May 2007 to February 2009, 1068 nonrandomized consecutive de novo native coronary lesions treated either with a PES (682 lesions) or SES were enrolled in this study, and a retrospective examination was conducted in April 2013. During that interval, the use ratio of drug-eluting stent (i.e. SES plus PES) was 94.2 %. By adjusting the baselines with a propensity score matching analysis produced 383 lesions in each arm, the incidence of the clinical endpoint (1500-day cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis) after placement of SES (2.1 %; mean follow-up, 1400 ± 290 days) was not significantly different from that in the PES group (2.6 %; 1394 ± 325 days, p = 0.637). SES did not relate to the clinical endpoint (hazard ratio 1.04; 95 % CI 0.29-3.76; p = 0.949). In the baseline-adjusted angiographic followed up lesions (n = 234 in each arm), the incidence of binary restenosis (percent diameter stenosis [%DS] >50 %) in the SES group (12.0 %; mean follow-up, 477 ± 281 days) was not significantly different from that in the PES group (14.5 %; 497 ± 341 days, p = 0.431). SES did not relate to binary restenosis (Odds ratio 0.73; 95 % CI 0.40-1.32; p = 0.295). In conclusion, the present propensity score matched lesion-based analysis firstly showed the statistical equivalent long-term clinical and angiographic outcomes after either SES or PES placement for de novo native coronary lesion in Japanese patients in a daily practice environment.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Propensity Score; Retrospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Clinical trials have demonstrated that the second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to the first-generation paclitaxel-eluting stent (PES) and is noninferior or superior to the sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from those to SES and PES because the pathology of CoCr-EES has not been described in humans.. A total of 204 lesions (SES=73; PES=85; CoCr-EES=46) from 149 autopsy cases with duration of implantation >30 days and ≤3 years were pathologically analyzed, and comparison of vascular responses was corrected for duration of implantation. The observed frequency of late and very late stent thrombosis was less in CoCr-EES (4%) versus SES (21%; P=0.029) and PES (26%; P=0.008). Neointimal thickness was comparable among the groups, whereas the percentage of uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%; P<0.0005) and PES (18.7%; P<0.0005). CoCr-EES showed a lower inflammation score (with no hypersensitivity) and less fibrin deposition versus SES and PES. The observed frequency of neoatherosclerosis, however, did not differ significantly among the groups (CoCr-EES=29%; SES=35%; PES=19%). CoCr-EES had the least frequency of stent fracture (CoCr-EES=13%; SES=40%; PES=19%; P=0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%; SES=5.5%; PES=1.2%).. CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less late and very late stent thrombosis compared with SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathological events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement.

Topics: Aged; Aged, 80 and over; Autopsy; Biocompatible Materials; Chromium Alloys; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Paclitaxel; Prevalence; Registries; Retrospective Studies; Sirolimus

Ostial right coronary artery (RCA) lesions are associated with a high restenosis rate after bare-metal stent implantation. However, long-term outcomes after drug-eluting stent (DES) implantation for ostial RCA lesions have not been adequately evaluated. Among 12824 patients enrolled in the j-Cypher registry, 5-year outcomes were compared between 397 patients with ostial RCA lesions, and 3716 patients with non-ostial RCA lesions treated with sirolimus-eluting stents (SES). Through 5-year follow-up, patients with ostial RCA lesions had a significantly higher cumulative incidence of target lesion revascularization (TLR) (28.2 versus 13.7 %, P < 0.0001) than those with non-ostial RCA lesions. After adjusting for confounders, excess TLR risk of the ostial group relative to the non-ostial group was significant for both early TLR within 1-year and late TLR beyond 1-year (HR 2.14 [95 % CI 1.59-2.84], P < 0.0001, and HR 1.58 [95 % CI 1.06-2.26], P = 0.02, respectively). Although the cumulative incidence of death was also significantly higher in the ostial group than in the non-ostial group (25.7 versus 14.4 %, P < 0.0001), the excess risk of the ostial group relative to the non-ostial group was no longer significant after adjusting for confounders (HR 1.25 [95 % CI 0.99-1.57], P = 0.07). SES implantation for ostial RCA lesions was associated with higher risk for TLR as compared with that for non-ostial RCA lesions. Restenosis, both early and late, remains an issue in coronary DES implantation for ostial RCA lesions.

Topics: Aged; Aged, 80 and over; Calcinosis; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Percutaneous Coronary Intervention; Registries; Risk Factors; Sirolimus; Treatment Outcome

Randomized trials and registries have shown that drug-eluting stents (DES) have an overall better performance than bare-metal stents in patients treated in the setting of both ST-segment and non-ST-segment elevation acute coronary syndromes, mainly by reducing restenosis. Whether or not the use of newer second-generation devices (vs. first-generation DES) differs in these high-risk patients remains to be determined.. In a single-centre prospective registry, 3266 patients underwent a percutaneous coronary intervention with at least one DES from January 2003 to December 2009. Of these, 1423 (43.6%) were treated in the setting of an acute coronary syndrome, using either first-generation-only DES [paclitaxel or sirolimus; n=923 (64.9%)] or second-generation-only [zotarolimus or everolimus; n=500 (35.1%)]. The occurrence of death from any cause, nonfatal myocardial infarction or target vessel failure (composite primary endpoint) was compared between these two groups; repeat revascularization of the index stented lesion and definite stent thrombosis [according to the academic research consortium (ARC) definition] were assessed as isolated secondary outcomes. At a median follow-up of 598 days (interquartile range 453-1206), the incidence of death was 10.7% (152), 136 patients (9.6%) had a new myocardial infarction and target vessel failure events occurred in 147 patients (10.3%). Disparity in the follow-up duration was accounted for by considering only the 1-year major adverse cardiac event rate (n=161; 11.3%). After adjustment for baseline characteristics using a Cox proportional hazard model, we could not find a significant difference in the incidence of the composite primary endpoint at 1-year between first-generation (10.8%) and second-generation DES (12.2%) [hazard ratio (HR): 1.1; 95% confidence interval (CI): 0.82-1.57, P=0.463], nor in the occurrence of repeat target lesion revascularization (3.6 vs. 4.4%; HR 1.35; 95% CI 0.77-2.34; P=0.293). In a per patient analysis, at 1 year, ARC-definite ST was documented in 1.0% of patients treated with second-generation DES versus 2.8% in those treated with first-generation DES (corrected HR 0.36; 95% CI 0.14-0.94; P=0.037), owing mostly to a higher difference in late ST.. Our results suggest that both first-generation and second-generation DES seem to be similarly effective in patients undergoing a percutaneous coronary intervention in the setting of acute coronary syndromes. However, newer second-generation devices may offer potential advantages because of a significantly lower incidence of ARC-definite ST.

Topics: Aged; Comparative Effectiveness Research; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Everolimus; Female; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Portugal; Proportional Hazards Models; Registries; Sirolimus; Stents; Treatment Outcome

To analyze the effect of paclitaxel-coated balloon (PCB) treatment on patients with drug-eluting stent (DES) restenosis.. In the Valentines I trial, treatment of coronary in-stent restenosis was effective and safe with the second-generation DIOR® PCB.. Valentines I prospectively enrolled 250 patients with in-stent restenosis (ISR); 76 patients (30.4%) had restenosis of a previous paclitaxel or limus DES. Patients underwent balloon angioplasty followed by PCB treatment. Clinical outcomes of patients with paclitaxel-eluting DES restenosis (n=34; 41 lesions) and limus-eluting (sirolimus, everolimus and zotarolimus) DES restenosis (n=42; 43 lesions) treated with DIOR® PCB were compared.. Baseline characteristics were similar. There were more diffuse lesions >20mm treated in paclitaxel- compared to limus-eluting DES restenosis (50% vs. 26.8%, p=0.032). Number of PCB used per patient (1.08±0.31 overall), mean PCB diameter (2.99±0.42mm overall), mean PCB length (24.4±11.9mm overall), and bailout stenting (2.4% vs. 4.7%) were similar (p=NS). At mean follow-up of 231±43days, major adverse cardiac events was 0% vs. 23.8% in paclitaxel- vs. limus-eluting DES restenosis (p=0.002), driven mainly by less target vessel revascularization (0% vs. 21.4%, p=0.004). Target lesion revascularization was 0% vs. 16.7% for paclitaxel- vs. limus-eluting DES restenosis (p=0.015).. In Valentines I, PCB use was more effective in patients with paclitaxel DES restenosis compared to limus DES restenosis, achieving better mid-term clinical outcomes. This suggests the efficacy of localized paclitaxel delivery to overcome paclitaxel resistance but not limus resistance due to different mechanisms of DES failure.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

This study sought to assess clinical significance of angiographic peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation in a large multicenter study with 5-year follow-up. The j-Cypher PSS substudy is a multicenter study including 5712 patients (7838 lesions) who underwent follow-up angiographic study within 12 months after SES implantation. Late acquired PSS was observed in 184 patients (3.2 %) or 194 lesions (2.5 %). Independent risk factors of PSS were chronic total occlusion and left anterior descending artery lesion, while negative risk factors were in-stent restenosis, diabetes mellitus, ≥70 years of age, and left circumflex coronary artery lesion. Cumulative incidence of definite very late stent thrombosis (VLST) at 4 years after the index follow-up angiography in lesions with PSS was significantly higher than that in lesions without PSS (5.3 versus 0.7 %, P < 0.0001). Late target-lesion revascularization (TLR) was also more frequently observed in the PSS group (13 versus 6.9 %, P = 0.01), while late TLR for restenosis excluding those TLR procedures for VLST tended to be higher in the PSS group (9.9 versus 6.3 %; P = 0.15). PSS found in 2.5 % of lesions within 12 months after SES implantation was associated with higher risk for subsequent VLST.

Topics: Aged; Anti-Inflammatory Agents; Blood Vessel Prosthesis Implantation; Contrast Media; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Japan; Male; Registries; Retrospective Studies; Risk Factors; Sirolimus

Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation.. Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%).. Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.

Topics: Aged; Cohort Studies; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Japan; Longitudinal Studies; Male; Metals; Middle Aged; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Registries; Retrospective Studies; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome

The SYNTAX score (SS) is used in preprocedural evaluation for percutaneous coronary intervention (PCI); it assesses the complexity of coronary lesions and predicts PCI outcome. However, the usefulness of the residual SS (rSS), which can be calculated after PCI and may reflect the completeness of revascularization, has not been fully investigated in an enriched PCI population.. The baseline SS and rSS were determined in 5,088 patients (3,046 everolimus-eluting stents and 2,042 sirolimus-eluting stents) from the EXCELLENT registry. The primary end point was 1-year patient-oriented composite end point (POCE), comprising all-cause death, myocardial infarction, and repeat revascularization. The mean baseline SS was 13.6 ± 9.1 and rSS was 4.7 ± 6.5. Residual SS tertiles were defined as rSS = 0 (42.7%), 0 < rSS < 7 (29.9%), and rSS ≥ 7 (27.4%). Increasing rSS tertiles had increasing 1-year POCE rates (5.2%, 8.1%, 12.4%; P < .001) mainly caused by the increase in repeat revascularization. Also, rSS was an independent predictor of 1-year POCE after multivariate analysis (P for trend < .001) and had better predictability in simple coronary lesions (baseline SS < 16). The clinical rSS, calculated by multiplying the rSS to a modified age, creatinine clearance, and ejection fraction score (age/ejection fraction + 1 for each 10 mL the creatinine clearance <60 mL/min), was also associated with 1-year POCE, with predictability similar to rSS (area under curve 0.610 vs 0.607, P = .634).. Greater residual coronary lesions after PCI with "limus" drug-eluting stent, as quantified by the rSS and the clinical rSS, are associated with increased risk of adverse cardiac events.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Registries; Republic of Korea; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Treatment Outcome

Detailed long-term changes of the neointima in sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) are still unclear.. We consecutively enrolled 14 patients (18 SES) and 12 patients (13 PES) who underwent optical coherence tomography (OCT) serially at eight months and 18 months after stent implantation. For 18 SES and 13 PES, OCT was used to visualise 2,486 and 1,361 stent struts at the eight-month and 2,199 and 1,309 stent struts at the 18-month follow-up, respectively. The OCT parameters, including incidence of uncovered and malapposed struts (uncovered and malapposed percentage), average neointimal hyperplasia thickness (NIH thickness) and %NIH volume obstruction, which was defined as ([mean NIH area*stent length]/[mean stent area*stent length])100, and qualitative analysis of the neointima were compared between SES and PES and also compared between the eight- and 18-month follow-up for SES and PES, respectively. The uncovered and malapposed percentage was significantly higher in SES than PES at the eight- and 18-month follow-up, and the NIH thickness and %NIH volume obstruction were lower in SES than PES at both follow-ups. The uncovered and malapposed percentage decreased in both SES and PES between the eight- and 18-month follow-up. Percent NIH volume obstruction and NIH thickness in SES significantly increased from the eight- to 18-month follow-up; however, those parameters significantly decreased in PES. The incidence of high signal with peri-strut low-intensity areas increased in SES but decreased in PES from the eight- to 18-month follow-up.. Uncovered and malapposed struts were reduced in both SES and PES, while the neointimal hyperplasia and qualitative changes showed different patterns.

Topics: Acute Coronary Syndrome; Aged; Antineoplastic Agents; Cohort Studies; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Disease Progression; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Retrospective Studies; Sirolimus; Tomography, Optical Coherence

The SYNTAX score has been proposed as a valuable tool to characterise coronary anatomy prospectively based on its complexity. This study evaluated the prognostic value on adverse outcomes of the residual SYNTAX score (rSS) in patients with complex lesions treated with an everolimus-eluting stent (EES).. One thousand eight hundred and fifty-one patients with small vessel (reference diameter <2.75 mm), long lesion (length >25 mm), or multivessel (>2 target vessels) disease who underwent percutaneous coronary intervention (PCI) with EES in the prospective SEEDS (A Registry To Evaluate Safety And Effectiveness Of Everolimus Drug Eluting Stent For Coronary Revascularization) trial were categorised into low (<6), mid (>6-<12) and high (>12) baseline SYNTAX score (bSS) groups, and into low (=0), mid (>0-<5) and high (>5) rSS groups. Mean bSS and rSS were 10.87±7.26 and 2.18±3.97, respectively; 64% of patients had complete revascularisation (rSS=0). At 12 months the primary outcome of ischaemia-driven target vessel failure (TVF, composite of cardiac death, target vessel myocardial infarction and ischaemia-driven target vessel revascularisation) was significantly higher in the high bSS and rSS groups than in the respective lower groups (p<0.01 for both). In multivariable analysis, rSS was an independent predictor of TVF (hazard ratio: 1.403, 95% confidence interval: 1.081 to 1.820, p=0.01).. Twelve-month TVF was significantly higher in the highest rSS group; rSS with a cut-off of 5 might therefore allow the risk stratification of patients with complex lesions treated with a second-generation drug-eluting stent (Clinical-Trials.gov identifier: NCT 01157455).

Topics: Aged; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Reproducibility of Results; Sirolimus; Treatment Outcome

This study aimed to investigate the long-term safety and efficacy of everolimus-eluting stents (EES) compared with other limus-eluting stents and bare metal stents (BMS) in ACS patients.. There have been concerns about the long-term safety of drug-eluting stents in the setting of acute coronary syndrome.. The study cohort included 1,612 patients presenting with acute coronary syndrome who underwent BMS, SES, E-ZES, or EES implantation. End points included probable or definite stent thrombosis and major adverse cardiovascular events (MACE), defined as a composite of all-cause death, Q-wave myocardial infarction, and target lesion revascularization up to 3 years.. The overall MACE rates were significantly higher for both BMS and SES, but not E-ZES, when compared with EES (EES vs. BMS: HR 2.68, 95% CI 1.91-3.78, P <0.001; EES vs. SES: HR 1.75, 95% CI 1.24-2.47, P = 0.001 and EES vs.. HR 1.08, 95% CI 0.65-1.77, P = 0.72). Stent thrombosis rates were similar for EES, E-ZES, and BMS but higher for SES throughout the 3-year follow-up (EES vs. BMS: HR 1.02, 95% CI: 0.31-3.35, P = 0.973; EES vs. SES: HR 4.90, 95% CI: 1.75-13.69, P = 0.002 and EES vs.. HR 1.63, 95% CI 0.37-7.31, P = 0.449).. There was an improvement in the long-term outcome for MACE with EES when compared to earlier-generation stents, but this was comparable with the 2nd-generation E-ZES. There was no additional risk of early or late stent thrombosis in EES when compared with BMS.

Topics: Acute Coronary Syndrome; Aged; Antineoplastic Agents; Cause of Death; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Washington

Stent fracture (SF) after drug-eluting stent implantation has become an important concern. The aim of this study was to assess the incidence, predictors, and clinical impact of SF after biolimus-eluting stent.. A total of 1026 patients with 1407 lesions undergoing the Nobori biolimus-eluting stent implantation and follow-up angiography within 9 months after index procedure were analyzed. SF was defined as complete or partial separation of the stent, as assessed by using plain fluoroscopy, intravascular ultrasound, or optical coherence tomography during the follow-up. We assessed the rate of SF and the cumulative incidence of clinically driven target lesion revascularization and definite stent thrombosis within 9 months. SF was observed in 58 (4.1%) of 1407 lesions and 57 (5.5%) of 1026 patients. Lesions with hinge motion (OR 8.90, 95% CI 3.84 to 20.6, P<0.001), tortuosity (OR 4.16, 95% CI 1.75 to 9.88, P=0.001), and overlapping stents (OR 2.41, 95% CI 0.95 to 6.10, P=0.06) were predictors of SF. Cumulative incidence of clinically driven target lesion revascularization within 9 months was numerically higher in the SF group than that in the non-SF group (12.0% versus 1.0%). Cumulative incidence of definite stent thrombosis within 9 months tended to be higher in the SF group than that in the non-SF group (1.7% versus 0.5%).. SF after biolimus-eluting stent occurs in 4.1% of lesions and appears to be associated with clinically driven target lesion revascularization.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Incidence; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Percutaneous Coronary Intervention; Prosthesis Design; Prosthesis Failure; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Topics: Angioscopy; Autopsy; Biopsy; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Fatal Outcome; Fibrosis; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Tomography, Optical Coherence

Topics: Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Male; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Everolimus; Female; Humans; Male; Percutaneous Coronary Intervention; Sirolimus; Ultrasonography, Interventional

Topics: Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus

Little is known on the "very" long-term incidence of major adverse cardiac events (MACE), target-lesion revascularization (TLR), target-vessel revascularization and stent thrombosis after sirolimus-eluting stent (SES) implantation. We present the first study to provide a 10-year clinical follow-up in an unselected patient population who underwent SES implantation.. We ran a systematic 10-year clinical follow-up in a series of 200 consecutive patients treated with unrestricted SES implantation between April 2002 and April 2003 in two Swiss hospitals. Outcomes and follow-up were obtained in all 200 patients. The cumulative 10-year MACE rate was 47% with all-cause death of 20%, cardiac death of 9%, myocardial infarction of 7%, TLR and target-vessel revascularization of 8% and 11% respectively. Academic Research Consortium-defined "definite and probable" stent thrombosis-rate was 2.5%. TLR risk was maximal between 3 to 6 years. New lesion revascularization increased throughout the study period.. Incidence of TLR was maximal 3 to 6 years after SES implantation and decreased thereafter. MACE and non-TLR revascularization rates steadily increased during the complete follow-up underlining the progression of coronary artery disease.

Topics: Aged; Combined Modality Therapy; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Failure; Sirolimus; Thrombosis; Treatment Outcome

Development of neoatherosclerosis (NA) has been reported to be a potential cause of late stent failure. However, the distribution of NA and its relationship with neovascularization (NV) and adjacent plaque characteristics remain unclear.. We investigated 167 stents (40 bare-metal stents, 84 sirolimus-eluting stents, and 43 everolimus-eluting stents) with optical coherence tomography. Each stent was divided into the proximal section (PS), mid section (MS) and distal section (DS). Neoatherosclerosis was defined as lipid-laden neointima or calcification inside stent. Adjacent plaque characteristics were evaluated within 5 mm proximal and distal reference segments.. Neoatherosclerosis was more frequent in PS and DS than in MS (PS 19.8% vs. MS 3.6% vs. DS 21%: PS vs. MS, P < .001: MS vs. DS, P < .001). Neovascularization in PS and DS was also more prevalent compared with that in MS (PS 15% vs. MS 5.4% vs. DS 13.8%: PS vs. MS, P = .001: MS vs. DS, P = .001). Neoatherosclerosis was more frequently observed in stents with intraintima NV (68.6% vs. 20.5%, P < .001). The incidence of NA was higher, when adjacent plaque was lipid (43.2% with lipid plaque vs. 12.2% without lipid plaque, P < .001).. Neoatherosclerosis occurs more frequently at PS and DS. Neoatherosclerosis was associated with NV and adjacent lipid plaque, suggesting potential interrelationship between development of NA and NV and adjacent plaque characteristics.

Topics: Aged; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Neovascularization, Pathologic; Plaque, Atherosclerotic; Prosthesis Failure; Sirolimus; Stents; Tomography, Optical Coherence

Topics: Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Sirolimus; Stents; Titanium

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Male; Metals; Paclitaxel; Sirolimus; Stents

Second-generation drug eluting stent (DES) implantation gradually replaced the first-generation DES in clinical practice. Whether the new DESs in use differ from one another, in terms of clinical outcomes, is still not known. We explored potential differences among DESs.. We followed 9584 consecutive patients undergoing percutaneous coronary intervention at our institution (2004-2012; mean follow-up, 2.8 years). Patients treated with bare-metal stent (BMS; n = 5599; 58.4%) were compared to 3985 DES counterparts (41.5%). The sirolimus-eluting stent (SES) served as the prototype for comparison to other DES types, using propensity matching. The primary outcome was a composite endpoint of total mortality, myocardial infarction, and clinically driven target vessel revascularization or coronary artery bypass graft. At 3 years, the composite endpoint was significantly lower in the DES vs. BMS group (17.9% vs. 25.3%; P<.001). Comparisons between SES and each of the five other stent types yielded no significant differences for the primary composite endpoint: SES vs. paclitaxel-eluting stent (n = 350 pairs; 18.1% vs. 17.7%; P=.70); vs. zotarolimus-eluting stent (n = 474 pairs; 21.8% vs. 23.2%; P=.35); vs. Resolute zotarolimus-eluting stent (n = 434 pairs; 16.9% vs. 11.7%; P=.70); vs. everolimus-eluting stent (n = 824 pairs; 14.2% vs. 14.1%; P=.60); and vs. biolimus-eluting stent (n = 117 pairs 13.7% vs. 13.4%; P=.60).. Cardiac prognosis did not differ between sirolimus and other DES types. The use of DES was associated with better clinical outcomes compared to BMS.

Topics: Aged; Comparative Effectiveness Research; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Long Term Adverse Effects; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Complications; Prognosis; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

Topics: Aged; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Male; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Paclitaxel; Sirolimus

Although percutaneous coronary intervention with everolimus-eluting stent (EES) implantation for native coronary artery disease has favorable results compared to first-generation drug-eluting stents, outcomes with EES for the treatment of in-stent restenosis (ISR) are unknown.. The Xience V USA is a prospective multicenter registry evaluating outcomes in patients treated with EES. Here, we present the 12-month clinical outcomes in patients who received EES for the treatment of ISR and non-ISR. The primary outcome was the composite of target lesion failure (cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization). Secondary outcomes were MI, target lesion revascularization (TLR), and stent thrombosis (ST).. In this registry, a total of 383 patients (64.4 ± 11.4 years; 68.4% male) received revascularization for single-vessel ISR and 4832 patients (64.4 ± 11.0 years; 69.0% male) received revascularization for non-ISR lesions. At 1 year, target lesion failure was 10.9% in the ISR group and 4.9% in the non-ISR group. MI, TLR, and definite ST rates were higher in the ISR group (MI, 2.2% ISR group and 1.6% non-ISR group; TLR, 10.3% ISR group and 2.9% non-ISR group; definite/probable ST, 1.98% ISR group and 0.36% non-ISR group). However, these differences ceased to exist when case-control matched patients in the non-ISR group were studied (target lesion failure, 8.8% ISR vs 7.4% non-ISR; cardiac death or MI, 2.7% ISR vs 1.4% non-ISR; TLR, 7.8% ISR vs 7.1% non-ISR; and definite/probable ST, 1.03% ISR vs 0.69% non-ISR).. The treatment of ISR with EES appears to be safe and efficacious at 1 year. Compared to the non-ISR group, target lesion failure was much higher, indicating a higher risk profile of these patients. However, these differences ceased to exist with case-controlled matching.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; United States

In-stent restenosis (ISR) is still a recognized clinical problem in the era of drug-eluting stent (DES). Some previous studies have suggested that circulating eosinophils play an important role in both restenosis and thrombosis after DES implantation. However, the contribution of eosinophils to the pathogenesis of ISR has not yet been concisely clarified.. We present the case of an 83-year-old male Japanese patient with ISR exacerbated by drug-induced severe eosinophilia. He had previous histories of coronary stent implantations by DES and was referred to our hospital because of erythema with severe eosinophilia (maximum was 6500/μl [48% of total white blood cell count]). Around the same time, the patient developed ISR, for which a stent was deployed 2 years earlier. Arterial wall injury due to the increase in circulating eosinophils was verified in several findings, such as the increase of D-dimer and brain natriuretic peptide. In addition, the histology of the resected tissue from erythema demonstrated that the nuclei of endothelial cells were swollen where eosinophils and lymphocytes heavily infiltrated into the extravascular space, suggesting the presence of vascular injury. This injury due to the increase in circulating eosinophils may have a marked impact on the pathologic process of ISR in DES implantation.. Just a few anecdotal reports are available of ISR occurring in the setting of hypereosinophilia. The clarification of the mechanism in this patient provides a new effective therapeutic strategy against ISR in the setting of DES implantation.

Topics: Aged, 80 and over; Biopsy; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Coronary Vessels; Diagnosis, Differential; Drug-Eluting Stents; Eosinophilia; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Paclitaxel; Prosthesis Design; Severity of Illness Index; Sirolimus; Tubulin Modulators

Limited data exist on contemporary sex-related differences in long-term outcomes of coronary patients receiving drug-eluting stents. In this study we evaluate differences for males (M) and females (F) in 2-year target lesion failure (TLF) in an unselected consecutive series of patients treated with everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) at a tertiary medical center.. Data on 348 consecutive patients (M 221, F 127) stented with EES and PES were retrospectively analyzed. The primary end point of the study was to compare sex-related outcomes in TLF, defined as the combined end point of cardiac death, nonfatal myocardial infarction, and target lesion revascularization (TLR). Secondary end points included TLR, target vessel failure, target vessel revascularization, acute stent thrombosis as defined by the Academic Research Consortium, and cardiac death. The cineangiograms of the first consecutive 162 patients (M 105, F 57) were independently reviewed by a cardiologist blinded to clinical outcome, and SYNTAX scoring was performed. Follow-up was achieved using medical records and/or phone calls and was censored at 2 years. Descriptive analysis was performed on all variables. Univariate analysis compared the M and F cohorts. Multivariate analysis using Cox regression was performed to determine independent predictors of TLF with time, including sex as an independent variable in the model.. M had more prior percutaneous coronary interventions and restenotic lesions and a higher prevalence of smoking. They also had longer length of disease and received more stents than F. F were older and had a higher prevalence of prior stroke. Angiographic complexity was not statistically different between the two groups, as judged by SYNTAX scoring (M 20.8±13.8, F 19.7±13.9, P=0.650). At 2-year follow-up, TLF was 27.4% and 24.8% (P=0.614) with no statistical difference between TLR (23.3% versus [vs] 21.6%), cardiac death (2.8% vs 3.2%), and definite and probable stent thrombosis (2.3% vs 0.0%) in M and F, respectively. Cox regression analysis using backward elimination showed that the number of stents per patient was the only independent predictor of TLF with time (hazard ratio 1.201, 95% confidence interval 1.126-1.280, P=0.001).. In this cohort of patients receiving EES and PES, M and F did not have statistically different outcomes at 2-year follow-up, consistent with recent reports in the current era of percutaneous coronary interventions.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Iowa; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Proportional Hazards Models; Prosthesis Design; Retrospective Studies; Risk Factors; Sex Factors; Sirolimus; Tertiary Care Centers; Time Factors; Treatment Outcome

Topics: Clinical Trials, Phase III as Topic; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Prosthesis Design; Randomized Controlled Trials as Topic; Sirolimus; Treatment Outcome

Topics: Acute Coronary Syndrome; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Percutaneous Coronary Intervention; Sirolimus

Topics: Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Registries; Sirolimus

We included into this study 112 patients with ischemic heart disease (IHD) and concomitant type 2 diabetes mellitus (DM) subjected to percutaneous coronary interventions with stenting. Everolimus and sirolimus eluting stents (EES and SES) were implanted in 54 (group 1) and 58 (group 2) patients, respectively. After 12 months in groups 1 and 2 rates of repeat target lesion revascularizations (TLR) were 5.5 and 8.6% (odds ratio - OR - 0.62, 95% confidence interval - CI - 0.14- 2.74, p = 0.72); acute myocardial infarctions (MI) - 3.7 and 5.2% (OR 0.71, 95% CI 0.11- 4.4, p = 0.94); deaths - 1.85 and 1.7% (OR 1.1, 95% CI 0.1- 17.6, p = 1.0), respectively. There was no significant difference between groups by rate of unfavorable cardiac events (composite of cardiac death, nonfatal MI, and clinically indicated TLR) - 11.1 and 15.5% in groups 1 and 2, respectively (OR 0.68, 95% CI 0.225- 2.059, p = 0.69). Rates of stent thrombosis also did not differ (1.85 and 3.4% in groups 1 and 2, respectively; OR 0.53, 95% CI 0.05- 6.0; p = 0.94). Thus the use of EES and SES in patients with IHD and type-2 DM was equally effective.

Topics: Aged; Coronary Restenosis; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Heart Function Tests; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Moscow; Myocardial Ischemia; Percutaneous Coronary Intervention; Postoperative Complications; Severity of Illness Index; Sirolimus; Treatment Outcome

Topics: Animals; Coronary Restenosis; Cytokines; Disease Models, Animal; DNA; Drug-Eluting Stents; Gene Expression Regulation; Immunosuppressive Agents; Postoperative Period; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Sirolimus

To study the role of eosinophil granulocytes in the development of restenosis after drug-eluting stent (DES) implantation.. The blood levels of eosinophils, eosinophil cationic protein (ECP), immunoglobulin E (IgE), and C-reactive protein (CRP) were compared in 170 patients with coronary heart disease (CHD) and stable angina who had undergone recoronarography within the first year after endovascular myocardial revascularization using DES. The blood level of eosinophils was determined by the results obtained employing the FACS Calibur flow cytofluorometer (Becton Dickinson, USA). That of ECP, IgE, and CRP was estimated by enzyme immunoassay by means of an Immulite-100 analyzer (Siemens, Germany). The data were presented as median (25th percentile and 75th percentile).. The blood eosinophil level was 272 (234; 292) cells/μl in patients with restenosis while that was 134 (85; 156) cells/μl in those without restenosis (p = 0.002). The plasma ECP level proved to be greater in the patients who had developed restenosis after DES implantation than in those who had not [17.7 (11.2; 24) and 9 (6.4; 12.9) ng/ml, respectively (p = 0.017). At 6 months after DES implantation, the level of ECP was significantly higher (8.6 (7.3; 9.7) ng/ml) than the baseline level (p = 0.04). Later on, there was an even greater increase in ECP levels. No significant changes were noted in blood ECP levels after bare stent implantation.. The findings suggest that there is a relationship between the occurrence of restenosis and the enhanced activity of eosinophil granulocytes in CHD patents after DES implantation.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Eosinophil Cationic Protein; Eosinophils; Female; Humans; Immunoglobulin E; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Statistics as Topic

The impact of underexpansion and minimal stent area (MSA) criteria in the second generation drug-eluting stents (DES) has not been addressed yet.. Using intravascular ultrasound (IVUS), we assessed the optimal cut-off values of post-stenting MSA to prevent in-stent restenosis (ISR). Poststenting IVUS data and 9-month follow-up angiography were available in 912 patients with 990 lesions: 541 sirolimus-eluting stents (SES), 220 zotarolimus-eluting stents (ZES) and 229 everolimus-eluting stents (EES).. For the prediction of angiographic ISR, the MSA of each DES was measured. The poststenting MSA was 6.4 ± 1.8 mm(2) in SES, 6.2 ± 2.1 mm(2) in ZES and 6.2 ± 2.1 mm(2) in EES. At the 9-months follow-up, the incidence of angiographic ISR was similar between SES (3.3%) vs. ZES (4.5%) vs. EES. (4.4%), (P = 0.53). Multivariable logistic regression analysis identified the post-stenting MSA as the only independent predictor of angiographic ISR in ZES (Odds ratio 0.722, 95% confidence interval 0.581-0.897, P = 0.001) and in EES (Odds ratio 0.595, 95% confidence interval 0.392-0.904, P = 0.015). The best MSA cut-off value was 5.5 mm(2) for the prediction of SES restenosis (sensitivity 72.2% and specificity 66.3%). For ZES, the optimal MSA predicting ISR was 5.3 mm(2) (sensitivity 56.7% and specificity 61.8%). For EES, the MSA <5.4 mm(2) predicted ISR (sensitivity 60.0% and specificity 60.0%).. As a preventable mechanism of ISR, smaller stent area predicted angiographic restenosis of the second generation DES as well as the first generation. The optimal cut-off values of post-stenting MSA for preventing restenosis were similar between ZES vs. EES vs. SES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Everolimus; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Topics: Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus

Previous intravascular ultrasound studies have shown that echolucent neointimal hyperplasia occasionally appears after bare-metal stent (BMS) or sirolimus-eluting stent (SES) implantation. Optical coherence tomography (OCT) studies have also demonstrated that paclitaxel-eluting stent (PES) restenosis exhibited similar images showing low signal intensity areas (LSIA) surrounding stent struts and three-layer appearance (TLA). The aim of the present study was to investigate the clinical significance of LSIA on OCT images in various types of stents. Fifty nine consecutive patients who underwent scheduled follow-up coronary angiography and OCT were enrolled. There was no significant difference in the prevalence of LSIA among the 3 stent groups (BMS 30%, SES 19%, PES 28%, P = 0.70). LSIA thickness was larger in the PES group than in the other stent groups (BMS 0.51 ± 0.21 mm, SES 0.35 ± 0.06 mm, PES 0.87 ± 0.19 mm, P < 0.01). The ratio of LSIA thickness to the neointimal thickness was also larger in PES compared with other stents (BMS 53 ± 9 %, SES 57 ± 8 %, PES 77 ± 5 %, P < 0.01). Also, LSIA thickness in patients with in-stent restenosis (ISR) was significantly larger than in those without ISR (0.37 ± 0.37 mm versus 0.12 ± 0.26 mm, P = 0.048). Our results suggest that LSIA might be involved in excessive neointimal formation, and that the healing response after PES implantation might be different from BMS or SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Humans; Hyperplasia; Immunosuppressive Agents; Japan; Male; Middle Aged; Neointima; Outcome Assessment, Health Care; Paclitaxel; Postoperative Complications; Prospective Studies; Sirolimus; Stents; Tomography, Optical Coherence; Tubulin Modulators

The aim of the present study was to assess the intravascular ultrasound predictors for angiographic edge restenosis after newer generation drug-eluting stent implantation. A total of 820 patients (987 lesions) who underwent newer generation drug-eluting stent placement (236 Endeavor zotarolimus-eluting stents, 246 Resolute zotarolimus-eluting stents, and 505 everolimus-eluting stents) with 9 months of angiographic surveillance were enrolled. The post-stenting angiographic and intravascular ultrasound images of 1,668 reference segments (681 proximal and 987 distal) were analyzed. Overall, 37% of angiographically normal proximal reference segments and 21% of angiographically normal distal reference segments had plaque burden >50%. In the overall cohort of 1,668 reference segments, 47 (2.8%) had 9-month angiographic edge restenosis (diameter stenosis >50%). Edge restenosis was predicted by a post-stenting reference segment plaque burden >54.5% (sensitivity 81%, specificity 80%) and a reference segment minimum lumen area of 5.7 mm(2) (sensitivity 72%, specificity 59%). The edge restenosis rate was 2.1% in the Endeavor zotarolimus-eluting stents, 2.4% in the Resolute zotarolimus-eluting stents, and 3.4% in the everolimus-eluting stents lesions (p = 0.311). The predictive cutoff of the reference plaque burden was 56.3% for Endeavor zotarolimus-eluting stents, 57.3% for Resolute zotarolimus-eluting stents, and 54.2% for everolimus-eluting stents. The criteria for residual plaque burden were similar between proximal and distal reference segments (56.4% vs 51.9%, respectively), but the minimum lumen area criteria were quite different (<7.1 mm(2) for proximal vs <4.8 mm(2) for distal reference segments). In conclusion, after newer drug-eluting stent implantation, edge restenosis was predicted by post-stenting reference segment plaque burden >55%.

Topics: Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Myocardial Infarction; Prosthesis Failure; Reproducibility of Results; Republic of Korea; Retrospective Studies; Sirolimus; Time Factors; Ultrasonography, Interventional

First generation drug-eluting stents (DES) are associated with reduced in-stent restenosis but significant increased risk of very late stent thrombosis (VLST). The absence of polymer in DES systems may reduce the occurrence of VLST. Optic coherence tomography (OCT) has been used for stent analysis as a surrogate safety endpoint. This study aimed to assess the long-term follow up of strut apposition and tissue coverage of BioMatrix DES by OCT. 20 patients undergoing BioMatrix DES (n = 15) or S-Stent BMS (n = 5) implantation were followed for at least 5 years and evaluated by quantitative coronary angiography, intravascular ultrasound, and OCT. The difference between the stent types was evaluated by nonparametric Mann-Whitney U test while categorical variables were evaluated by Fisher exact test. Rates of in-stent late loss were similar between groups [0.40 (0.21;0.77) vs. 0.68 (0.66; 0.82) mm, p = 0.205, for BioMatrix and S-Stent, respectively]. The vessel, stent and lumen volumes did not differ between groups. Patients treated with BioMatrix had significantly less stent obstruction [5.6 (4.4;9.7) vs. 28.6 (24.7;29.0) %, p = 0.001]. OCT analysis of 12 stents (Biomatrix = 9 and S-Stent = 3) demonstrated 126 (8.7 %) uncovered struts in the BioMatrix group compared to 23 (4.0 %) in the S-Stent group (p = 0.297), being the majority of them well apposed (117/126 and 21/23, respectively, p = 0.292). Only 9 (0.6 %) struts in the DES and 2 (0.4 %) struts in the BMS groups were simultaneously uncovered and malapposed (p = 0.924). BioMatrix DES was associated with lower rates of in-stent obstruction, and similar percentage of neointimal coverage on struts and of complete strut apposition.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

We propose a modified simultaneous kissing stenting technique (MSKS) based on systematic implantation of a protective stent in the proximal main vessel (PMV) proximally to the bifurcation before simultaneous kissing stenting (SKS).. SKS has been proposed in large-size coronary vessel bifurcation lesions (BLs) when the PMV can accommodate two stents. SKS implies, however, low-pressure simultaneous final balloon inflations to avoid retrograde PMV dissection or rupture and therefore may not ensure optimal final stent apposition.. From January 2005 to May 2008, a total of 97 patients with 100 BLs (true bifurcation in 92%) who underwent MSKS were enrolled in a prospective registry. Drug-eluting stents were used for distal main vessel and side branch. Drug-eluting or large-size bare-metal stents were used as proximal protective stents.. Immediate procedural success rate was 100%. Global restenosis rate was 10% (5% in the main vessel and 8% in the side branch) at follow-up angiogram performed at 7 months in all patients (100%). No patient had early or late stent thrombosis. Two cases of non-fatal very late stent thrombosis occurred at 46 and 64 months. Over a mean 4.5-year follow-up period, target lesion revascularization rate was 11%, with only 3% driven by clinical ischemia.. Protective stent systematic implantation in the PMV represents a newly modified SKS technique that allows safe finalization of the procedure by high-pressure kissing balloon final inflation, ensuring optimal stent apposition with high immediate procedural success and low rates of long-term events.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Male; Metals; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Retrospective Studies; Sirolimus; Stents; Treatment Outcome

To evaluate the incidence, time course and predictors of late target lesion revascularisation (TLR) (between one and two years) as compared to early TLR (<1 year) following everolimus-eluting stent implantation in patients enrolled in the SPIRIT V study.. The SPIRIT V single-arm study enrolled a total of 2,700 patients (n=2,663 intent-to-treat) with de novo coronary artery lesions undergoing EES implantation. Patients were evaluated at 30 days, one year and two years following the index procedure. All patients who had a clinically driven TLR (not associated with stent thrombosis) were allocated to either the early or the late group. Clinical, angiographic and procedural data were recorded and predictors of early vs. late TLR were assessed by logistic regression analysis. There were no significant differences in baseline demographics and risk factors between the two groups with the exception that patients in the late TLR group were significantly older (68.5 ± 8.5 years vs. 63.5 ± 8.9 years, p=0.022). At two years, only 2.7% (70/2,562) experienced a TLR unrelated to a stent thrombosis event with 1.6% (43/2,627) occurring within one year of the index procedure and 1.1% (27/2,562) occurring between one and two years. There were no differences between the groups in terms of clinical outcomes. Age ≥70 years was the only variable which independently predicted late TLR (OR=4.80 [1.69-13.63], p=0.0032).. In this large registry without angiographic follow-up, early (<1 year) and late (>1 year) TLR rates were exceedingly low and thereby confirm the previous findings of randomised controlled studies. Age (>70 years) emerged as the only predictor of late TLR.

Topics: Age Factors; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Humans; Incidence; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The BASE-ACS trial demonstrated an outcome of titanium-nitride-oxide-coated bioactive stents (BAS) that was statistically non-inferior to that of everolimus-eluting stents (EES) at 12-month follow-up, in patients presenting with acute coronary syndrome (ACS) who underwent early percutaneous coronary intervention (PCI). We explored a post-hoc analysis of the 12-month outcome of the BASE-ACS trial in the subgroup of patients with ST-elevation myocardial infarction (STEMI) versus non-ST-elevation ACS (non-STEACS).. A total of 827 patients with ACS (321 STEMI) were randomly assigned to receive either BAS or EES. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR) at 12-month follow-up.. The 12-month cumulative incidence of the primary endpoint was similar between the two subgroups (9% versus 9.5%, in STEMI versus non-STEACS patients respectively, P=0.90). The 12-month rate of cardiac death was significantly higher in the STEMI subgroup as compared with the non-STEACS subgroup (2.8 versus 0.6%, respectively, P=0.01). However, the rates of non-fatal MI, ischemia-driven TLR, definite stent thrombosis, and non-cardiac death were all statistically matched between the two subgroups (P>0.05 for all).. In the current post-hoc analysis of the BASE-ACS trial based on the infarction type, the 12-month outcome of patients who underwent early PCI for ACS was slightly worse in the setting of STEMI as compared with non-STEACS, as reflected by a significantly higher rate of cardiac death.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Coated Materials, Biocompatible; Combined Modality Therapy; Coronary Restenosis; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Heart Diseases; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Sirolimus; Titanium; Treatment Outcome

Sirolimus-eluting stents (SES) are reported to be associated with reduced late lumen loss (LLL), resulting in less frequent restenosis when compared to bare-metal stent. The current study aimed to assess the difference in LLL between SES with biodegradable and with permanent polymer.. From March 2010 to June 2011, 300 consecutive patients having only biodegradable polymers or permanent polymer SES for all diseased vessels were included. Serial quantitative coronary analysis was performed on both the "in-stent" and "segment" area, including the stented segment, as well as both five mm margins proximal and distal to the stent. The primary endpoint was the LLL defined as the minimal lumen diameter (MLD) post-stenting minus the MLD at nine-month after the indexed procedure.. LLL was comparable between the two stents. Importantly, LLL for the distal segment (median 0.05 mm, interquartile 0 to 0.09 mm) was less severe compared with in-stent (median 0.13 mm, interquartile 0.08 to 0.18 mm) and proximal segment LLL (median 0.12 mm, interquartile 0.06 to 0.14 mm, all P < 0.001). In general, the LLL was associated with the post-procedure MLD (b = 0.28, P = 0.002), hyperlipidemia (b = 0.14, P = 0.021), and calcified lesions (b = 0.58, P = 0.001). The R(2) and Radj of the multiple regression model were 0.651 and 0.625, respectively.. SES with either biodegradable or permanent polymer had lower value of LLL. The small amount of LLL at the distal segment possibly contributed to the less distal edge stenosis.

Topics: Aged; Aspirin; Clopidogrel; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Polymers; Regression Analysis; Sirolimus; Ticlopidine

The aim of this study is to evaluate the acute and long-term outcomes of ostial stentings among bare-metal stents (BMS), sirolimus-eluting stents, and paclitaxel-eluting stents.. According to the CAPTAIN (Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions) registry, from November 1995 to June 2011, 420 patients with ostial lesions were treated using BMS implantations (243 patients with 247 lesions), CYPHER implantations (77 patients with 77 lesions), or TAXUS implantations (100 patients with 104 lesions).. Compared with the CYPHER and TAXUS groups, the BMS group had larger late loss (0.29±0.53, 0.64±0.78, and 1.30±0.79 mm, respectively, P=0.006) and restenosis rate (6, 8, and 33%, respectively, P<0.001). During the long-term follow-up, the BMS group had higher target lesion revascularization than the CYPHER and TAXUS groups (17, 4, and 6%, respectively, P=0.002). The cardiac event-free survival rate, as determined by the Kaplan-Meier analysis, was also lower in the BMS group than in the CYPHER and TAXUS groups (55, 86, and 76%, respectively, P<0.001).. Intracoronary stenting with drug-eluting stent for ostial lesions was associated with lower angiographic restenosis and late loss, and a more favorable long-term clinical outcome than BMS.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Disease-Free Survival; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Paclitaxel; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome

We investigated whether sirolimus-eluting stents (SES) are superior to next-generation zotarolimus-eluting stents (ZES) in treating patients with total coronary occlusions (TCO).. In a prospective, randomised trial we compared the SES with the zotarolimus-eluting stent (ZES; Endeavor or Resolute) after successful recanalisation of TCO. During the first phase of the trial, 51 patients were assigned to receive the SES and 46 patients to receive the Endeavor ZES. In the second phase we randomised 103 patients to the SES group and 104 patients to the Resolute ZES group. The primary endpoint was in-segment late lumen loss at eight-month follow-up. At eight months, patients in the SES group had less in-segment and in-stent late loss as compared to the Endeavor group: -0.13±0.3 mm vs. 0.27±0.6 mm (p=0.0002) and -0.13±0.5 mm vs. 0.54±0.5 mm (p<0.0001), respectively. In contrast, the SES and the Resolute ZES showed comparable amounts of in-segment (-0.03±0.7 mm vs. -0.10±0.7 mm, p=0.6) and in-stent (0.03±0.8 mm vs. 0.05±0.8 mm, p=0.9) late loss.. In the treatment of TCOs, the SES was associated with superior angiographic outcomes compared to the Endeavor ZES. On the other hand, the SES and the Resolute ZES showed comparable angiographic outcomes.

Topics: Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Prospective Studies; Sirolimus; Treatment Outcome

Saphenous vein grafts (SVGs) are prone to an aggressive atherosclerotic process, and the efficacy of drug-eluting stents (DES) in treating this is still debated. In recent years, second-generation DES have been increasingly used in SVG intervention. The main objective of this study was to compare midterm clinical outcomes between first- and second-generation DES in SVGs because data regarding the use of second-generation DES in SVG are lacking. Patients treated with first-generation DES (127 patients with 143 lesions) and those treated with second-generation DES (84 patients with 100 lesions) were included in the study. Major adverse cardiac events, defined as the composite of all-cause death, myocardial infarction, and target vessel revascularization, as well as target vessel revascularization and target lesion revascularization separately, were evaluated at 30-day, 12-month, and 18-month follow-up. Baseline characteristics were similar between the 2 groups. Older grafts were treated with second-generation DES (11.6 ± 5.3 vs 14.3 ± 6.0 years, p = 0.001). Stent length was longer in the first-generation group (34.1 ± 25.1 vs 30.5 ± 19.4 mm, p = 0.006), and maximum balloon diameter was smaller in the second-generation group (3.42 ± 0.42 vs 3.30 ± 0.41 mm, p = 0.003). Embolic protection device use was higher in the second-generation DES group (55.2% vs 72.0%, p = 0.012). At 18-month follow-up, rates of major adverse cardiac events, target vessel revascularization, and target lesion revascularization for the first- and second-generation groups were 24.4% versus 20.2% (p = 0.479), 18.1% versus 14.2% (p = 0.465), and 15.0% versus 10.7% (p = 0.373), respectively. In conclusion, second-generation DES are at least comparable with first-generation DES with regard to clinical outcomes at midterm follow-up.

Topics: Aged; Antineoplastic Agents; Cause of Death; Coronary Artery Bypass; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paclitaxel; Postoperative Complications; Prosthesis Design; Reoperation; Sirolimus; Veins

The aim of this study was to evaluate the strut apposition and neointimal coverage of Supralimus-Core stent struts at 4 months after implantation using optical coherence tomography (OCT).. The Supralimus-Core OCT study is a retrospective, single-center study evaluating strut apposition and neointimal coverage with OCT at 4 months after stent implantation. A total of 12 patients, who had 15 stents implanted were included in the study. The OCT was obtained using a C7-XR FD-OCT (frequency-domain OCT) intravascular imaging system. Strut apposition, neointimal hyperplasia (NIH) thickness and stent coverage on each stent strut were evaluated.. A total of 2870 struts and 1950 frames were analyzed from 15 stents. Average stent length was 29.3 mm. Average reference vessel diameter was 2.64 mm. Among 12 patients, 3 (25.0%) patients were with diabetes, 4 (26.7%) type B2 and 10 (66.7%) type C lesions. The apposed and covered struts were 2787 (97.11%), whereas malapposed and covered struts were 3 (0.10%), apposed and uncovered 49 (1.71%) and malapposed and uncovered 31 (1.08%). Mean NIH thickness was 155.1±55.2 µm.. The present study suggests that Supralimus-Core stent has a favorable vascular healing pattern at 4 months after stent implantation in terms of stent-strut coverage and strut apposition. This information indicates that the Supralimus-Core stent is a promising solution for decreasing late stent restenosis and preventing stent thrombosis.

Topics: Aged; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies; Risk Factors; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

In drug-eluting stent (DES) restenosis, the contribution of drug hyporesponsiveness is poorly defined. We sought to evaluate if, in the setting of treatment for in-stent restenosis, the relative efficacy of sirolimus-eluting stents (SES) and of paclitaxel-eluting stents (PES) depends on the underlying substrate in which the stents are implanted, i.e., on whether the restenosis occurs within bare metal stents or within SES.. We pooled data from the ISAR-DESIRE and ISAR-DESIRE 2 randomised trials and analysed outcomes in SES-treated and PES-treated patients. In all, 650 patients were included. Angiographic follow-up was available for 87% of patients. In SES-treated patients, both late loss (LL) and percentage diameter stenosis (%DS) were lower in patients treated for bare metal stent restenosis compared with SES restenosis (0.21±0.59 mm versus 0.41±0.66 mm, p=0.007; 27.6±19.4% versus 34.0±20.9%, p=0.015, respectively). In PES-treated patients, LL and %DS were similar in patients treated for bare metal stent restenosis compared with SES restenosis (0.48±0.59 mm versus 0.39±0.71, p=0.47; 33.5±22.2% versus 32.7±18.6%, p=0.75, respectively). Similarly, in terms of overall clinical efficacy, in SES-treated patients clinical outcomes were better in patients with bare metal stent restenosis compared with SES restenosis while in PES-treated patients outcomes were similar in both groups. At multivariate analyses the use of SES to treat restenosis within SES was predictive of both higher LL and %DS.. The efficacy of sirolimus-eluting but not paclitaxel-eluting stents is significantly reduced when used for treatment of SES restenosis as compared to bare metal stent restenosis. The lower antirestenotic efficacy following SES implantation in patients with SES restenosis may support a role for drug resistance in restenosis within these stents.

Topics: Coronary Restenosis; Drug Resistance; Drug-Eluting Stents; Humans; Metals; Paclitaxel; Sirolimus; Treatment Outcome

The impact of lesion calcium on long-term outcomes after drug-eluting stent implantation has not been adequately addressed. In 10,595 patients (16,803 lesions) who were exclusively treated with sirolimus-eluting stents in the j-Cypher registry, 5-year outcomes were compared between patients with ≥1 lesion with moderate or severe calcification (the calcium group) and those with noncalcified lesions only (the noncalcium group). Analyses were stratified by hemodialysis (HD) status (non-HD stratum [calcium n = 3,191, noncalcium n = 6,824] and HD stratum [calcium n = 415, noncalcium n = 165]). Adjusted risk in the calcium group for death and target lesion revascularization was significant in the non-HD stratum (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.18 to 1.52, p <0.0001, and HR 1.2, 95% CI 1.07 to 1.36, p = 0.003) and the HD stratum (HR 1.4, 95% CI 1.06 to 1.86, p = 0.02, and HR 2.25, 95% CI 1.51 to 3.36, p <0.0001). Risk for definite stent thrombosis tended to be higher in the calcium group in the HD stratum (HR 5.05, 95% CI 0.66 to 38.9, p = 0.12) but not in then non-HD stratum (HR 1.16, 95% CI 0.81 to 1.67, p = 0.41). The use of rotational atherectomy in patients with severe calcification did not have a significant impact on the cumulative incidence of target lesion revascularization in the non-HD stratum (17.7% [n = 268] with vs 18.2% [n = 588] without rotational atherectomy, p = 0.68) and the HD stratum (54.7% [n = 115] with vs 51.9% [n = 118] without rotational atherectomy, p = 0.19). In conclusion, regardless of HD status, patients with calcified lesions have increased long-term risk for death and target lesion revascularization after sirolimus-eluting stent implantation.

Topics: Aged; Aged, 80 and over; Atherectomy, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Prospective Studies; Registries; Renal Dialysis; Sirolimus; Treatment Outcome; Vascular Calcification

Topics: Absorbable Implants; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Humans; Male; Middle Aged; Prosthesis Design; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Failure

Drug-eluting stents have been developed to reduce the risk of restenosis after angioplasty. To facilitate the adhesion of a poly(lactic acid) (PLA) overlayer loaded with rapamycin (20 wt%), a biodegradable macromonomer based on poly(lactic acid) (HEMA-PLA) was grafted onto the metallic stent by electrografting in a one-step reaction involving the immobilization of aryl diazonium onto the metal followed by an in situ surface electro-polymerization. The HEMA-PLA coating was chemically characterized. Mechanical performance during stent expansion was tested. Morphology examinations showed a strong adhesion of PLA topcoat in the presence of the electrografted layer. Biocompatibility and degradation of the coating were studied in vitro and in vivo in rabbit iliac arteries. These 28 days implantations resulted in a minimal inflammatory process with a partial degradation of the coating. These results suggest that this kind of anchoring of a biodegradable layer shows great potential for drug-eluting stents.

Topics: Angioplasty; Animals; Arteries; Biocompatible Materials; Cell Adhesion; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Electrochemistry; Humans; Inflammation; Lactic Acid; Male; Metals; Polyesters; Polymers; Rabbits; Sirolimus; Stents; Stress, Mechanical

This study was designed to prospectively evaluate the safety and efficacy of the 38-mm Resolute zotarolimus-eluting stent (R-ZES). Drug-eluting stents with long lengths are needed to ensure coverage of long lesions in some patients. Patients recruited from the RESOLUTE US and RESOLUTE Asia studies were implanted with at least one 38-mm R-ZES. Up to 2 lesions (in separate vessels) could be implanted with length ≤35 mm and a reference vessel diameter of 3.0 to 4.2 mm. The primary end point was 1-year target lesion failure, defined as cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The 1-year target lesion failure rate using 1 vessel per patient was compared with a performance goal (19%) derived from historical data. There were 223 patients enrolled (n = 269 lesions). The mean age was 60.9 ± 10.9 years, 79% were men, and 38% had diabetes. Target lesion failure rate using a single-vessel analysis was 4.5%, and the upper limit of the 1-sided 95% confidence interval (7.5%) was less than the performance goal of 19%. A secondary analysis using all lesions resulted in a target lesion failure rate of 5.4% (upper limit of 1-sided 95% confidence interval, 8.6%). Baseline characteristics and clinical outcomes were similar between patients with and without diabetes. The rate of probable or definite stent thrombosis was 0.9%. In conclusion, the 38-mm length of the R-ZES was found to be safe and effective with a low rate of target lesion failure and stent thrombosis and no differences in outcomes between patients with and without diabetes.

Topics: Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

This study sought to assess the clinical safety and effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in patients with in-stent restenosis (ISR) from 2 large trials.. ISR treatment is associated with higher rates of subsequent cardiac events compared with treatment of de novo lesions. Although drug-eluting stents (DES) are an option, second-generation DES are largely untested in the treatment of ISR.. A total of 3,489 patients were pooled from the RAC (RESOLUTE All Comers) trial and the RESOLUTE International (RINT) registry. Two-year clinical endpoints included clinically driven target lesion revascularization (TLR), target lesion failure (TLF), cardiac death (CD), target vessel myocardial infarction (TVMI), combined CD or TVMI (CD/TVMI), and Academic Research Consortium definite and probable stent thrombosis (ST).. Overall, 281 patients (8.1%) received an R-ZES for ISR. Two-year TLR and TLF rates were significantly higher in ISR patients than in non-ISR patients (TLR: 12.7% vs. 4.3%, p = 0.003; TLF: 17.4% vs. 9.4%, p = 0.007); however, the CD/TVMI rate was not (6.9% vs. 6.1%, p = 0.711). Seven ISR patients had ST. Two-year outcomes by ISR stent type were similar: bare-metal stent (BMS)-ISR TLR was 12.5% and TLF was 17.2%; DES-ISR TLR was 13.0% and TLF was 18.8%. CD/TVMI was 7.3% and 7.2% for BMS-ISR and DES-ISR, respectively.. Using R-ZES to treat ISR appears equally safe in BMS-ISR and DES-ISR, with CD/TVMI rates comparable to 2-year outcomes in other clinical trials. Although revascularization rates are still higher in ISR lesions, the R-ZES offers an effective alternative for treatment of BMS-ISR and DES-ISR. (Randomized, Two-Arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; and RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [RINT]; NCT00752128).

Topics: Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Propensity Score; Prosthesis Design; Randomized Controlled Trials as Topic; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Coronary artery disease (CAD) is still the leading cause of death throughout the world. Metal stents are used to widen narrowed arteries. In addition, drug-eluting stents (DES) are widely implanted to decrease the risk of in-stent restenosis. Commercially available polymer-based DES suffer from some limitations. To avoid these drawbacks, the use of self-assembled monolayers (SAMs) in DES has recently been investigated. In this study, methyl- and carboxyl-terminated mixed SAMs on gold (Au) surfaces were successfully prepared. The samples were characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and contact angle goniometry (CA). The mixed SAM-coated surfaces were evaluated for everolimus delivery. The drug release in PBS was studied using high performance liquid chromatography (HPLC) and quartz crystal nanobalance (QCN). The results were compared with those related to homogenous SAM-coated surfaces. Significant differences (p<0.05) were found in the amount of drug eluted between the mixed SAM and the homogenous one. The findings are promising for the application of mixed SAMs in DES.

Topics: Chromatography, High Pressure Liquid; Coated Materials, Biocompatible; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Everolimus; Gold; Humans; Materials Testing; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Photoelectron Spectroscopy; Quartz Crystal Microbalance Techniques; Sirolimus; Spectroscopy, Fourier Transform Infrared; Surface Properties

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Neointima; Sirolimus; Tomography, Optical Coherence

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

We aimed to evaluate the mid-term outcomes of resolute zotarolimus-eluting stent (R-ZES) implantation for in-stent restenosis (ISR).. There has been a paucity of data regarding the effects of new-generation drug-eluting stent to treat ISR.. From 2009 to 2010, a total of 98 patients with 98 ISR lesions were prospectively enrolled after R-ZES implantation for the treatment of ISR. Among 98 patients, 73 patients underwent follow-up angiography at 9 months. Serial intravascular ultrasound (IVUS) at both postprocedure and 9 months was evaluated in 55 patients. The overlapped segment of R-ZES was defined as the portion of R-ZES superimposed on previous stent.. Late loss and binary restenosis rate were 0.3 ± 0.5 mm and 5.5% at 9 months. On IVUS, the percentage of neointimal volume and maximum percentage of neointimal area were 3.9 ± 6.3% and 17.3 ± 15.5%, respectively. There was no significant change of vessel volume index between postprocedure and 9 months (16.9 ± 4.7 mm³ /mm vs. 17.1 ± 4.6 mm³ /mm, P = 0.251). Late-acquired incomplete stent apposition was observed in 5 (5/55, 9.1%) cases. Compared with nonoverlapped segments of R-ZES, the overlapped did not show larger neointimal volume index (0.3 ± 0.5 mm³ /mm vs. 0.2 ± 0.3 mm³ /mm, P = 0.187) on 9-month IVUS. During follow-up (median, 353 days), repeat target-lesion revascularization was performed in four cases, but there were no death or stent thrombosis.. This study suggested that R-ZES implantation for the treatment of ISR was effective up to 9 months and showed favorable vascular responses on serial IVUS assessment.

Topics: Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

New generation DES are effectively used in all spectrum of coronary artery diseases (CAD) and are replacing earlier DES and BMS. Biolimus A9™-eluting stent is a new generation DES containing the anti-proliferative drug biolimus A9™ incorporating a biodegradable abluminal coating that leaves a polymer-free stent after drug release enhancing strut coverage while preventing neointimal hyperplasia. A retrospective data analysis was done in patients treated with DES, with a major share of Biolimus A9™ (BA9™) drug-eluting stents (DES) at Bombay Hospital, Mumbai. A total of 158 patients with 219 lesions were treated with DES, comprising Biolimus A9-eluting stent and others and the major adverse cardiac events (MACE) rate and stent thrombosis (ST) at 1, 6, 12 months and 24 months were analyzed. Mace rate was 3.16% for average follow-up of 19 months. There were 3 cases of ST (2 of acute and 1 of subacute onset) and one non-cardiac death reported during this time. This retrospective data demonstrates good one- and two-year clinical safety and efficacy of DES, especially of BioMatrix stents in real world setting.

Topics: Absorbable Implants; Adult; Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cause of Death; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; India; Male; Middle Aged; Myocardial Infarction; Polymers; Prosthesis Design; Prosthesis Failure; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Sirolimus; Survival Rate; Treatment Outcome; Young Adult

To compare the edges vascular response, we analyzed the intravascular ultrasound (IVUS) parameters after implantation of the sirolimus-eluting stent (SES) or the paclitaxel-eluting stent (PES).. Two hundred-two angina patients (123 men; 61.5 ± 9.2 years of age, SES: n = 91, PES: n=111) were enrolled. Both edge segments of the stent were analyzed. The change (Δ) of each parameter at follow-up was calculated.. The edge restenosis rate was higher in the PES group. However, the Δ Vessel, Δ Plaque and Δ Lumen volume at 5mm edge segments were not different between the two groups except the Δ Plaque volume at the distal segment, higher in the PES than the SES group (6.6 ± 15.7 vs. 1.0 ± 13.1mm(3), P=.016). In the PES group, lumen area at the both 1mm edge segments decreased because of plaque progression (proximal, 1.9 ± 1.5 to 2.2 ± 2.0mm(2), P=.095; distal, 0.6 ± 1.1 to 1.0 ± 1.4mm(2), P=.018) with negative remodeling (proximal, 9.9 ± 2.4 to 9.4 ± 2.6mm(2), P=.004; distal, 7.6 ± 2.4 to 7.2 ± 2.4mm(2), P=.052). Conversely, lumen area at these segments increased due to plaque regression (proximal, 3.2 ± 1.8 to 2.1 ± 1.6mm(2), P=.000; distal, 1.5 ± 1.4 to 0.9 ± 1.3mm(2), P=.000) even though there was negative remodeling in the SES group (proximal, 10.1 ± 2.4 to 9.6 ± 2.3mm(2), P=.019; distal, 7.8 ± 2.3 to 7.5 ± 2.3mm(2), P=.074). The Δ Plaque and Δ Lumen area at the both 1mm edge segments were more prominent in the PES group.. Compared to SES, PES was associated with luminal reduction accompanied by plaque progression with negative remodeling at edge segments.

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

The safety and efficacy of the Promus Element stent have been recently demonstrated in a selected population from one randomized trial. The aim of this study was to describe the initial clinical experience with the everolimus eluting platinum chromium stent (Promus Element) in unselected patients from a real life nationwide registry.. The Promus Element DES was compared to all other DES implanted in Sweden (with more than 500 implants) from November 2009 to March 2011. The results were assessed using Cox regression.. A total of 13,577 stents (Promus Element, n=2724, Cypher, n=782; Endeavor, n=747; Taxus Liberté, n=1393, Xience V/Promus, n=4832, Resolute, n=1566, Xience Prime, n=4832) were implanted at 8375 procedures. At one year the restenosis rate in the Promus Element was not significantly different from the overall DES group (2.8% vs. 2.7%, adjusted HR:1.17, 95% CI: 0.75-1.75). A significantly lower restenosis rate was observed in the Promus Element when compared with Endeavor (2.8% vs. 5.8%; adjusted HR: 0.44; 95% CI: 0.26-0.74). The stent thrombosis (ST) rate at one year was not significantly different in the Promus Element as compared with the overall DES group (0.2% vs. 0.5% adjusted HR: 0.59; 95% CI: 025-1.40). ST rate was significantly lower as compared with Endeavor stent (0.2% vs. 0.8%; HR: 0.24; 95% CI: 0.08-0.67).. In a large unselected population the Promus Element stent appears to be safe and effective with a low risk of restenosis and ST.

Topics: Aged; Angioplasty, Balloon, Coronary; Chromium; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Platinum; Registries; Sirolimus; Sweden; Treatment Outcome

Our aim was to compare the outcomes of a same versus different drug-eluting stent (DES) implantation strategy for the treatment of DES instent restenosis (ISR).. The absence of clear data renders the treatment of DES ISR one of the most challenging situations in interventional cardiology.. We identified all cases of DES ISR treated with a second DES between January 2004 and January 2009. The lesions were divided into those treated with the same DES as the initial one that restenosed and those treated with a different DES. The main end-point was repeat target lesion revascularization (TLR).. We included 116 patients with a total of 132 lesions. The patient population was highly complex: 55.5% with diabetes, 56% with type-C lesions, 15.9% with lesions previously stented with BMS and 18.2% with fluoroscopic evidence of stent fracture. A same and different stent strategy was conducted in 41 lesions (31%) and 91 lesions (69%), respectively. Overall TLR was 31.1% and occurred in 46.3% of patients treated with the same stent and 24.4% of those with a different stent (P = 0.012). Multivariable analysis found same stent strategy (OR 2.84, 95%CI 1.23-6.57;P = 0.014) and occurrence of stent fracture (OR 4.03, 95%CI 1.33-12.01;P = 0.012) to be the only independent predictors of TLR after a median follow-up of 20.4 [12.1-30.2] months.. In highly complex lesions, DES implantation for DES ISR is linked to a high need of future revascularization. An association between implanting a DES type other than the original and lower rate of TLR is suggested.

Topics: Aged; Angioplasty, Balloon, Coronary; Confidence Intervals; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Ontario; Paclitaxel; Patient Selection; Prosthesis Failure; Registries; Retreatment; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Survival Analysis; Treatment Outcome

Because systemic inflammation after coronary intervention places patients at increased risk of subsequent cardiac events, we aimed to compare clinical outcomes and chronic serum inflammation markers of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) in hemodialysis patients. Paclitaxel-eluting stents and SES were implanted in 36 patients with 46 lesions, and 32 patients with 40 lesions, respectively. In addition to 1-year major adverse cardiac event (MACE) rates, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), neopterin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were also compared before and 9 months after percutaneous coronary intervention (PCI). The incidence of MACE was significantly lower in the PES group than in the SES group (11.1 vs. 25.0 %, respectively, P = 0.042), mainly due to the reduction of target lesion revascularization in the PES group (6.5 vs. 17.5 %, P = 0.003). The logarithm of hs-CRP as well as IL-6 decreased significantly 9 months post-PCI compared with pre-PCI in the PES group (hs-CRP: 3.65 ± 0.35 vs. 2.91 ± 0.48, P = 0.007; IL-6: 6.73 ± 3.66 vs. 2.61 ± 2.29, P = 0.017) but not in the SES group (hs-CRP: 3.33 ± 0.29 vs. 3.42 ± 0.27, P not significant; IL-6: 6.08 ± 4.97 vs. 5.66 ± 4.29, P not significant). However, neopterin, ICAM-1, and VCAM-1 remained unchanged both pre-PCI and 9 months post-PCI in both groups. Moreover, MACE were less frequent in patients with decreased hs-CRP levels 9 months post-PCI compared with patients without decreased hs-CRP levels (P = 0.002) in all patients. Paclitaxel-eluting stents appear to be more effective than SES in reducing MACE rates, especially target lesion revascularization, and may be able to stabilize local inflammatory changes of target lesions specifically in patients on hemodialysis. Thus PES, which inhibit in-stent restenosis and cardiac events in hemodialysis patients, may play an important role in suppression of chronic inflammatory response in target lesions as compared with SES. Chronic continuous inflammation plays an important role after implantation of both types of stent with regard to in-stent restenosis in patients on hemodialysis.

Topics: Aged; Biomarkers; C-Reactive Protein; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Inflammation; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Middle Aged; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Renal Dialysis; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Vascular Cell Adhesion Molecule-1

Drug-eluting stents (DES) have significantly improved the rate of target vessel revascularization in comparison with bare metal stents. DES fracture was not reported in multicenter randomized clinical trials, but several case reports of DES fracture have been published, mostly with sirolimus-eluting stents. DES fracture is associated with stent restenosis and thrombosis. We report a zotarolimus-eluting stent fracture in an aortocoronary saphenous vein graft (SVG) bypass. The patient presented with chest pain and a non-ST-elevation myocardial infarction. He underwent cardiac catheterization that showed a complete fracture of a zotarolimus-eluting stent in the ostium of a sequential SVG to the diagonal and obtuse coronary arteries. His management included coronary angioplasty and retrieval of the proximal fractured segment. We discuss the potential causes for this stent fracture and suggest caution when using a DES in an ostial location of a SVG bypass, especially in a highly mobile vessel.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Male; Myocardial Infarction; Prosthesis Failure; Retreatment; Risk Assessment; Saphenous Vein; Severity of Illness Index; Sirolimus; Treatment Outcome

To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model.. Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high.. Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment.. There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1.. PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans.

Topics: Acrylic Resins; Animals; Cardiac Catheters; Cardiovascular Agents; Chemistry, Pharmaceutical; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Equipment Design; Infusions, Parenteral; Lactic Acid; Nanoparticles; Neointima; Percutaneous Coronary Intervention; Polyesters; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Porosity; Sirolimus; Swine; Time Factors; Ultrasonography, Interventional

The putative effects of changes in mean strain and cyclic strain amplitude on vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) were examined. Subsequently, a quantitative measure of vSMC growth was obtained to determine the prolonged effect of changes in mechanical burden following bare-metal stent (BMS) and sirolimus drug-eluting stent (DES) deployment in vitro. Bovine aortic vSMCs were exposed to prolonged cyclic strain using a Flexercell(TM) Tension system and a novel Sylgard(TM) phantom vessel following stent implantation before the level of vSMC proliferation and apoptosis was assessed by FACS analysis, cell counting, and immunocytochemistry. Physiological cyclic strain (5%) decreased vSMC proliferation and increased apoptosis in a temporal manner. There was no significant difference in cell growth following exposure to varying mean strains with similar amplitude. In contrast, exposure to varying strain amplitudes with similar mean strains resulted in significant differences in cell proliferation and apoptosis. In parallel studies, the level of vSMC proliferation and cell survival was significantly increased within low amplitude, high mean strain regions of a phantom vessel following BMS implantation when compared to regions of higher strain amplitude upstream and downstream of the stent, respectively. Moreover, the level of vSMC growth within the stented region was significantly attenuated following implantation of a sirolimus-coated DES independent of significant changes in cell survival. Cyclic strain amplitude is an important regulator of vSMC growth capacity within a stent and is a target for inhibition using a sirolimus-coated DES.

Topics: Animals; Apoptosis; Cattle; Cell Count; Cell Proliferation; Coronary Restenosis; Drug-Eluting Stents; Flow Cytometry; Humans; Linear Models; Microscopy, Fluorescence; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phantoms, Imaging; Sirolimus; Stress, Mechanical; Time Factors

Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Follow-Up Studies; Humans; Male; Paclitaxel; Pneumonia; Prednisolone; Radiography, Thoracic; Retreatment; Risk Assessment; Sirolimus; Tomography, X-Ray Computed; Treatment Outcome

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies; Sirolimus

Although the use of drug-eluting stents (DES) has reduced the rate of restenosis, some problems remain regarding the usefulness of DES in small coronary arteries in addition to late thrombosis and a longer duration of dual-antiplatelet therapy. We considered 335 patients with 698 lesions who underwent DES or bare-metal stent (BMS) implantation, and randomly selected 172 DES and 124 BMS lesions that had undergone a complete data analysis and evaluation. Patients had a history of stable angina with at least 1 lesion with 50% diameter stenosis in a vessel and with a successfully minimum stent implantation (stent diameter=2.5mm). The baseline characteristics including the clinical presentation and cardiovascular risk factors were similar between the DES and BMS groups, except for the percentage of dyslipidemia (DL). Pre-procedure reference vessel diameter (RVD pre) in the DES group was significantly smaller than that in the BMS group (p<0.01), and stent length in the DES group was significantly longer (p<0.01). There was no significant difference in the cumulative incidence of major adverse cardiac events including the target lesion revascularization rate, whereas in-stent restenosis (ISR) in the DES group was significantly lower than that in the BMS group. In a multivariate analysis of ISR, diabetes mellitus, prior percutaneous coronary intervention, and DES use in clinical background were identified as independent predictors of ISR. In addition, RVD pre, stent length, and DES use in angiographical background were also identified. In conclusion, DES use is an independent predictor of ISR, although the DES group included more severely diseased small coronary arteries.

Topics: Aged; Comparative Effectiveness Research; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Multivariate Analysis; Paclitaxel; Percutaneous Coronary Intervention; Registries; Risk Factors; Sirolimus; Stents; Treatment Outcome

Percutaneous coronary intervention for lesions with small vessel diameter may have high event rates. Although drug-eluting stents reduce the risk of restenosis, the long-term efficacy of drug-eluting stent implantation in small vessels is unclear.. We reviewed the data of Cypher Stent Japan Post-Marketing Surveillance Registry including 2356 lesions of 1959 patients, and retrospectively investigated the angiographic outcomes at 8 months, and the clinical outcomes at 1800 days after sirolimus-eluting stent (SES) implantation in vessels with diameter less than 2.5mm (small vessel group) compared to that with diameter of 2.5mm or more (non-small vessel group). The rate of major adverse cardiac events (MACE) at 1800 days was slightly higher in the small vessel group than in the non-small vessel group, but not statistically significant (24.4% vs 21.0%, p=0.086). The rate of target lesion revascularization was higher in the small vessel group than in the non-small vessel group (10.2% vs 6.4%, p=0.004). The rate of stent thrombosis was almost the same in the two groups. Multivariate Cox hazard model analysis revealed that a vessel diameter less than 2.5mm was not an independent risk factor for MACE.. SES implantation for vessels with diameter less than 2.5mm is safe and provides good long-term outcomes.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Product Surveillance, Postmarketing; Proportional Hazards Models; Registries; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

The purpose of this study was to examine the angiographic and clinical results of stent full metal jacket in treating long lesions using everolimus-eluting stents (EES).. Data are lacking regarding the use of EES for this lesion subgroup.. From 2007 to 2011, 77 symptomatic patients who had severe coronary stenoses necessitating implantation of stents with total length longer than 60 mm were treated with overlapping EES.. The mean age of patient was 61 ± 11 years with male predominance (66%). Diabetes mellitus was seen in 35 (45.5%) patients. Majority of patients had class III angina with normal heart function. On average, 3.1 stents were implanted per lesion; the mean stent size and length were 2.70 ± 0.28 mm and 82 ± 16 mm. Restudy angiography was performed on 71 patients (72 lesions) at 8.9 ± 2.5 months. Angiographic restenosis was seen in 9 (12.5%) lesions; the lesion length and late loss were 67 ± 15 mm and 0.4 ± 0.6 mm, respectively. The use of intravascular ultrasound has been found to be a predictor of less restenosis (P = 0.02; HR: 0.02; CI: 0.01-0.59). The in-hospital and 1 year major adverse cardiac event rates were 7.8% and 13%. The annual cardiac death rates were 2.6%, 3.4%, and 5.3% in the first 3 years.. The use of EES full metal jacket for long lesions is only associated with good short-term clinical and angiographic outcomes. Long-term follow-up has revealed a high cardiac death rate which may necessitate prolongation of dual antiplatelet therapy.

Topics: Cardiotonic Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Sirolimus

To investigate the characteristics and one-year outcomes following sirolimus-eluting CYPHER Select Plus stent (SES) implantation in small (SmVD) and non-small vessel disease (NSmVD) in the international e-SELECT registry.. Large-scale registry data are lacking on DES outcomes in SmVD treatment.. There were 4,700 SmVD (at least one vessel with estimated reference vessel diameter [RVD] < 2.5 mm, excluding 283 patients with unknown RVD vessels) and 10,139 NSmVD only patients.. The SmVD population was older, with more women, diabetics, and vessels treated, higher mean Charlson Comorbidity Index score (CCI), shorter lesions, and less STEMI presentation. The 1-year stent thrombosis (ST) rate (primary end-point), was significantly higher (1.3% vs. 0.7%) in SmVD versus NSmVD, mainly driven by early events. One-year major adverse cardiac event (MACE), myocardial infarction (MI), and clinically indicated target-lesion revascularization (TLR) rates were significantly higher in SmVD although death and major bleeding rates were similar in both groups. Complication rates were similar between pure (3,188 patients; only RVD < 2.5 mm) and mixed (1,795 patients; some RVD < 2.5 mm or unknown RVD) SmVD. Multivariate predictors for 1-year MACE in SmVD included saphenous vein graft or bifurcation lesions, major bleeding, any antiplatelet therapy discontinuation within 1 month, age, number of stents implanted, CCI, acute coronary syndrome, and insulin-dependent diabetes mellitus.. SES implantation for SmVD occurs more frequently in women, diabetics, and those with multivessel disease and comorbidities. One-year ST, MACE, MI, and clinically indicated TLR rates are higher, although low overall, in SmVD or mixed SmVD patients while death rates are similar to NSmVD.

Topics: Aged; Cohort Studies; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Postoperative Complications; Registries; Sirolimus; Survival Analysis; Treatment Outcome

First-generation drug-eluting stents have been proven to be very effective for the treatment of bare-metal stent in-stent restenosis (BMS ISR). Efficacy of second-generation drug-eluting stents in this setting remains less well defined. This study compared 3-year clinical outcomes after treatment of BMS ISR using second-generation everolimus-eluting stents (EES) to first-generation paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES).. This was a retrospective observational study. A total of 264 consecutive patients with BMS ISR underwent percutaneous coronary intervention using EES (75 patients), PES (95 patients), or SES (94 patients) from 2003 to 2009. The primary endpoint of the study was survival free of major adverse cardiac events (MACE) at 3 years. Secondary endpoints were survival free of need for revascularization of the target lesion and definite stent thrombosis. Clinical follow-up could be obtained in 99% of patients.. Baseline clinical and angiographic parameters were comparable between the three groups. MACE at the 3-year follow-up were 27, 30, and 27%, for the EES, PES, and SES groups, respectively (P=0.874). The target lesion revascularization rates for EES, PES, and SES groups were 15, 20, and 23%, respectively (P=0.429). Rates of definite stent thrombosis at the 3-year follow-up were comparable between the three groups at 0, 2.1, and 1.0%, respectively (P=0.437). Rates of myocardial infarction and death were also similar between the three groups. Diabetes mellitus was the only independent predictor of MACE at the 3-year follow-up (odds ratio=1.14, 95% confidence interval 1.00-1.30; P=0.038), whereas renal insufficiency was the only independent predictor for death (odds ratio=1.10, 95% confidence interval 0.850-1.274; P=0.011).. Second-generation EES is as effective and safe as the first-generation PES or SES in the treatment of BMS ISR. Diabetes mellitus is the only independent predictor for MACE at the long-term follow-up.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Myocardial Revascularization; Paclitaxel; Percutaneous Coronary Intervention; Renal Insufficiency; Retrospective Studies; Sirolimus; Stents

We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses.. One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before - after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P<0.001). Backscatter and signal intensity were significantly higher with BMS (P<0.05 and P<0.001 respectively). The NITA reduction rate was significantly greater in the layered and heterogeneous groups than in the homogeneous group (P<0.01).. The morphologic OCT patterns of the NIT in ISR differed significantly between DES and BMS, probably reflecting pathologic differences. Layered and heterogeneous tissues might respond better than homogeneous tissue to simple balloon dilatation, suggesting a possible direction for OCT-based ISR treatment strategies. 

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Incidence; Male; Metals; Middle Aged; Neointima; Paclitaxel; Retrospective Studies; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Follow-Up Studies; Humans; Male; Middle Aged; Prosthesis Failure; Retreatment; Severity of Illness Index; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence

We describe a 42-year-old man with very late stent thrombosis (VLST) 35 months after implantation of a sirolimus-eluting stent (SES). Three months after the VLST episode, a follow-up angiography showed a formation of peri-stent coronary artery aneurysm. Sixty-five months after SES implantation, the patient suffered an out-of-hospital cardiac arrest. We performed spasm provocation test using acetylcholine to evaluate coronary vasomotor response and the coronary segments adjacent to the SES showed significant vasoconstriction. Intracoronary pretreatment of Rho-kinase inhibitor, fasudil, markedly attenuated acetylcholine-induced vasoconstriction. This report documents a unique case suffering from multiple fatal complications after SES implantation.

Topics: Adult; Coronary Aneurysm; Coronary Angiography; Coronary Restenosis; Coronary Vasospasm; Drug-Eluting Stents; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Sirolimus; Time Factors; Ultrasonography, Interventional

The development of drug-eluting stents (DES) has dramatically reduced the incidence of in-stent restenosis. Stent fracture (SF) of DESs, however, has recently emerged as a rare but serious complication, which may lead to acute coronary syndrome or sudden cardiac death. DES fracture results from metal fatigue and vessel hemodynamic stress on the stent strut, due to markedly reduced neointimal formation. Although actual incidence of SF is not known, previous reports have demonstrated that SF rates are specific to each DES type. In this report, 2 cases of fracture of a Nobori stent are described, with insights into the mechanisms of SF and strategies for its successful management.

Topics: Aged, 80 and over; Angina Pectoris; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Prosthesis Failure; Sirolimus

Restenosis after percutaneous coronary intervention (PCI) is still a great concern even in the recent drug-eluting stent (DES) era. As less invasive and sensitive parameter to detect restenosis is needed, this study was aimed to assess whether the clinical implication of temporal change in plasma BNP levels might be a useful indicator of restenosis after DES implantation.. 847 consecutive patients who underwent elective PCI using silorimus-eluting sent (SES) between 2005 and 2009 were analyzed. Primary endpoint was subsequent target-lesion revascularization (TLR) after PCI. There was no significant difference in either baseline (TLR+vs. TLR-: 107.2 ± 172.2 vs. 96.2 ± 175.5 pg/mL, P=0.53) or follow-up plasma B-type natriuretic peptide (BNP) levels (TLR+vs. TLR-: 88.6 ± 111.6 vs. 68.5 ± 226.0 pg/mL, P=0.35) between patients with and without subsequent TLR. Conversely, ratio of follow-up to baseline BNP was significantly higher in patients with TLR (TLR+vs. TLR-: 1.55 ± 1.58 vs. 1.07 ± 1.04, P<0.001). Multivariate analysis using logistic regression showed log transformed BNP-ratio was an independent predictor of TLR (adjusted odds ratio (aOR): 1.94, 95%CI: 1.42-2.66, P<0.001). A closer relationship between BNP elevation greater than 2-fold and subsequent TLR was found (aOR: 2.69, 95%CI: 1.27-5.69, P<0.009). Furthermore, propensity score matching analysis showed that the incidence of subsequent TLR was significantly higher in patients with BNP elevation (P<0.001).. Serial measurement of plasma BNP levels and its change might be a useful approach to predict restenosis in patients without typical chest symptoms receiving SES.

Topics: Aged; Biomarkers; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Revascularization; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Predictive Value of Tests; Retrospective Studies; Sirolimus

To report the four-month and nine-month angiographic results as well as one-year clinical follow-up from the first-in-man study with the silicon carbide and sirolimus-eluting bioabsorbable polymer (poly-L-lactic acid (PLLA) polymer) -coated cobalt-chromium Orsiro stent.. A group of 30 patients with documented myocardial ischaemia related to a single de novo coronary stenosis up to 22 mm in length, in vessels with a 2.5 to 3.5 mm reference diameter, and between >50% and <90% diameter stenosis were enrolled at two sites. The primary endpoint of the study was in-stent late lumen loss at nine months. The secondary endpoints included major adverse cardiac events (MACE) at one year defined as the composite of cardiac death, ischaemia-driven target lesion revascularisation (TLR) and target vessel myocardial infarction (MI). Procedural success was 100%. Angiographic late lumen loss was 0.12±0.19 mm and 0.05±0.22 mm at four and nine months respectively. At one-year clinical follow-up, the composite MACE was 10% with one patient who died from cardiac death and two patients who had ischaemia-driven target lesion revascularisation. There was no report of MI or stent thrombosis.. The Orsiro drug-eluting stent demonstrated potency with low rates of in-stent neointimal hyperplasia and cardiovascular events but warrants further evaluation in a larger population cohort with longer follow-up time points.

Topics: Aged; Carbon Compounds, Inorganic; Chromium Alloys; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Incidence; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Silicon Compounds; Sirolimus; Treatment Outcome

The pathogenesis of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The purpose of this study is to analyse tissue characterizations of neointima in restenosis lesions after sirolimus-eluting stent (SES), comparing with those after bare metal stent (BMS) using integrated backscatter intravascular ultrasound (IB-IVUS).. A total of 54 consecutive patients who had ISR lesions after SES (n = 20) or BMS (n = 34) implantation were enrolled. For tissue characterization of neointima, IB-IVUS was performed by cross-sectional (at the minimum lumen area) and volumetric (within the stented segment) analyses. In addition, angiographic patterns of restenosis were evaluated with division into focal and diffuse. The focal angiographic pattern of restenosis was predominantly observed in the SES group (SES vs. BMS; 80.0 vs. 26.5%; P = 0.0001), whereas the diffuse pattern was more common in the BMS group (SES vs. BMS; 20.0 vs. 73.5%; P = 0.0001). On both cross-sectional and volumetric IB-IVUS analyses, the neointimal tissue in restenosis lesions after SES implantation had a significantly larger percentage of lipid tissue (cross-sectional: 23.3 ± 12.7 vs. 15.7 ± 11.9%; P = 0.033; volumetric: 22.8 ± 10.4 vs. 16.3 ± 7.0%; P = 0.008) and a significantly smaller percentage of fibrous tissue compared with that after BMS implantation (cross-sectional: 73.6 ± 11.6 vs. 82.0 ± 11.2%; P = 0.011, volumetric: 73.8 ± 9.5 vs. 80.5 ± 6.7%; P = 0.004).. This IB-IVUS study indicates that larger amounts of lipid tissue are present in neointima of SES when compared with BMS, suggesting that neoatherosclerosis may in part be responsible for ISR after SES implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Metals; Middle Aged; Neointima; Prospective Studies; Prosthesis Design; Prosthesis Failure; Retreatment; Sirolimus; Stents; Ultrasonography, Interventional

Sirolimus-eluting stent (SES) has shown a significant efficacy in reducing restenosis after percutaneous coronary interventions. However, an increase in total number of SES use along with targeting more complex lesions generated a large number of SES restenosis. This study aimed to investigate the clinical and angiographic outcomes of different revascularization strategies for SES restenosis.. A total of 176 lesions in 149 patients were included in the study. Fifteen patients underwent coronary artery bypass graft surgery (CABG group) and the remaining patients were treated with percutaneous coronary intervention (PCI). Stent reimplantation was performed in 88 patients (Stent group), whereas 46 patients received balloon therapy (Balloon group). Among 176 lesions, major cardiac adverse event (MACE) occurred in 41 lesions (23.3%) during a median follow-up of 310 days (interquartile range: 146-517 days). The Kaplan-Meier method with a log-rank test revealed no significant difference in MACE rates between the three groups (6%, 25%, 26%, p = 0.13; CABG group, Stent group, Balloon group, respectively). However, when the Balloon group and Stent group were combined together as a PCI group, PCI group had a significantly higher rate of MACE compared with the CABG group (p = 0.04). In addition, angiographic restenosis was significantly less prevalent in the CABG group when compared with the other two groups (8%, 57%, 46%, p = 0.006; CABG group, Stent group, Balloon group, respectively).. CABG surgery for patients with SES restenosis is associated with the better clinical outcomes as well as better angiographic outcomes when compared with that of PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Coronary Restenosis; Death; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Postoperative Complications; Radiography; Retrospective Studies; Sirolimus; Treatment Outcome

We sought to compare the safety and effectiveness of everolimus-eluting stents (EES) versus first generation drug-eluting stents (FG-DES; sirolimus-eluting stent [SES] or paclitaxel-eluting stent [PES]).. In 2,126 patients undergoing percutaneous coronary intervention (PCI), we compared the 2-year incidence of stent thrombosis (ST) and target vessel revascularization (TVR) between the EES versus FG-DES groups. Secondary end-points included all-cause death, myocardial infarction (MI), death or MI, and major adverse cardiovascular events (MACE, including death, MI, ST, or TVR). Further, we evaluated these end-points in 2 propensity-matched subgroups: EES versus SES; EES versus PES.. Complete 2-year follow-up was available in 1,911 (90%) patients. Compared to FG-DES, implantation of EES was associated with trends towards lower ST (0.9% vs. 2.8%, P = 0.068) and TVR (3.8% vs. 7.2%, P = 0.052), which persisted after adjustment for baseline differences (for ST, adjusted hazard ratio, HR 0.32; 95% confidence interval, 95% CI 0.10-1.02, P = 0.053; for TVR, HR 0.40; 95% CI 0.22-0.75, P = 0.004). Compared to SES, EES implantation was associated with lower TVR and a trend towards lower ST. Compared to PES, EES implantation was associated with less ST and TVR and trends towards lower death/MI and MACE. In the EES group, no ST was seen after the first 3 months.. The use of EES compared to FG-DES appears to be associated with reductions in ST and TVR at 2-year follow-up. Improved outcomes with EES are observed in comparison with SES as well as PES.

Topics: Aged; Aged, 80 and over; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Registries; Sirolimus; Thrombosis; Treatment Outcome

Late in-stent restenosis (ISR) is an important clinical issue in the drug-eluting stent era. Autopsy studies have reported different underlying mechanisms between early ISR and late ISR. The aim of the present study was to compare the neointimal tissue appearance between early ISR (<1 year) and late ISR (>1 year) after sirolimus-eluting stent (SES) implantation using optical coherence tomography (OCT).. We examined the neointimal tissue appearance in 48 ISR lesions after SES implantation [30 early ISR lesions (8±1 months after stenting) and 18 late ISR lesions (34±14 months after stenting)] by OCT. ISR was defined as percent diameter stenosis more than 50% within the stented segment in angiography. Lipid-rich neointima was characterized by signal-poor regions with diffuse borders. Thin-cap fibroatheroma (TCFA)-like neointima was defined by lipid-rich neointima with cap thickness 65 μm or less.. In the OCT findings, heterogeneous neointima was more often observed in the late ISR group compared with the early ISR group (89 vs. 43%, P=0.002). Although the frequency of intraluminal thrombus was not different between the two groups (P=0.085), the frequency of lipid-rich neointima (83 vs. 27%, P<0.001), TCFA-like neointima (39 vs. 10%, P=0.028), microchannels within neointima (67 vs. 27%, P=0.007), and neointimal disruption (33 vs. 3%, P=0.008) was significantly higher in the late ISR group.. In the present OCT study, it was found that atherosclerotic progression of neointima, such as lipid-rich neointima, TCFA-like neointima, microchannels, and neointimal disruption, was more often observed in late ISR lesions after SES implantation compared with early ISR ones.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Disease Progression; Drug-Eluting Stents; Female; Humans; Lipids; Male; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

We aimed to uncover the protein changes of coronary artery in-stent restenosis (ISR) tissue in minipigs with and without streptozotocin-induced diabetes mellitus by quantitative 2-dimensional fluorescence in-gel electrophoresis (2D-DIGE), and to investigate the influences of crucial proteins identified, particularly adipocyte fatty acid binding protein (AFABP), in human arterial smooth muscle cells.. Sirolimus-eluting stents were implanted in the coronary arteries of 15 diabetic and 26 nondiabetic minipigs, and angiography was repeated after 6 months. The intima tissue of significant ISR and non-ISR segments in both diabetic and nondiabetic minipigs was analyzed by 2D-DIGE and MALDI-TOF/TOF mass spectrometry. AFABP level was significantly increased in ISR tissue than in non-ISR tissue in both diabetic and nondiabetic minipigs, with level being higher in diabetic ISR than in nondiabetic ISR tissue. In human arterial smooth muscle cells, overexpression of AFABP significantly altered phenotype and promoted growth and migration, with effects more prominent in high-glucose than in low-glucose medium, whereas AFABP knockdown inhibited these effects. AFABP overexpression increased reactive oxygen species production by upregulating the expression of NADPH oxidase subunits Nox1, Nox4, and P22 through multiple pathways, with elevation of downstream gene cyclin D1, matrix metalloproteinase-2, and monocyte chemoattractant protein-1. However, AFABP-induced effects were inhibited by diphenyleneiodonium, pathway inhibitors, and small interfering RNA. In addition, the supernatant from AFABP-expressing human arterial smooth muscle cells and recombinant AFABP also promoted cellular growth and migration.. This study has demonstrated that AFABP is significantly increased in coronary artery ISR segments of both diabetic and nondiabetic minipigs. Increased AFABP expression and secretory AFABP of human arterial smooth muscle cells promote growth and migration via reactive oxygen species-mediated activation.

Topics: Animals; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Drug-Eluting Stents; Electrophoresis, Gel, Two-Dimensional; Enzyme Inhibitors; Fatty Acid-Binding Proteins; Fluorescence; Glucose; Humans; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NADPH Oxidases; Neointima; NF-kappa B; Oxidative Stress; Percutaneous Coronary Intervention; Phenotype; Reactive Oxygen Species; RNA Interference; RNA, Messenger; Signal Transduction; Sirolimus; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; STAT3 Transcription Factor; Swine; Swine, Miniature; Time Factors; Transcription Factor AP-1; Transfection; Up-Regulation

This study examined whether sirolimus-eluting stent (SES) implantation exerts an antiproliferative action on a bare metal stent (BMS) placed distally in the same coronary artery.. Diffusion of sirolimus into flowing coronary blood may cause accumulation of this drug in the coronary bed beyond the distal edge of an SES.. We analyzed data from 115 consecutive patients with ischemic heart disease who were treated with two overlapping stents without a gap in the same coronary artery for a long de novo lesion. The distal stent was a 2.25 mm BMS in all patients, and the proximal stent was an SES in 73 patients (SES-BMS group) and a BMS in 42 patients (BMS-BMS group). Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) were performed at stent implantation and 8 months later.. Clinical and procedural variables were comparable between the two groups. QCA and IVUS showed that the SES-BMS group had less luminal late loss and a lower percent of in-stent volume obstruction in the distal BMS compared with the BMS-BMS group. Furthermore, compared with the BMS-BMS group, the SES-BMS group had less in-stent restenosis (23.3 vs. 54.8%, P < 0.0005) and target lesion revascularization (21.9 vs. 50.0%, P < 0.005).. SES implantation just proximal to a BMS inhibits neointimal proliferation in the BMS, when both stents are implanted in the same coronary artery to treat a de novo lesion.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Metals; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Recent studies reported favorable angiographic and clinical outcomes after everolimus-eluting stent (EES) implantation. However, there were no studies to assess vascular responses after EES implantation using optical coherence tomography (OCT). Therefore, the OCT findings in EES were investigated and compared with those in sirolimus-eluting stent (SES). Follow-up OCT studies were performed in 110 lesions (40 EES and 70 SES) of 104 patients at 9 months after stent implantation. The strut apposition, neointimal hyperplasia (NIH) thickness and stent coverage on each stent struts were evaluated. The mean NIH thickness was significantly greater in EES-treated lesions than in SES-treated lesions (115 ± 52 μm vs. 89 ± 58 μm, P = 0.001, respectively). The percentage of uncovered strut was significantly smaller in EES-treated lesions than in SES-treated lesions (4.4 ± 4.7% vs. 10.5 ± 12.7%, P = 0.016, respectively). There was no significant difference in the percentage of malapposed strut between the two groups (0.4 ± 0.8% in EES vs. 1.7 ± 4.5% in SES, P = 0.344). The incidence of intracoronary thrombus was significantly lower in EES-treated lesions than in SES-treated lesions (5.0% vs. 34.3%, P < 0.001, respectively). EES showed a significantly lower incidence of uncovered stent struts and intracoronary thrombus than SES in 9-month follow-up OCT examination. Compared to SES, EES might have more favorable vascular responses after stent implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Predictive Value of Tests; Registries; Republic of Korea; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

We evaluated the predictive factors for recurrent restenosis lesions treated on two previous occasions with sirolimus-eluting stents (SES).. Angiography data related to recurrent SES restenosis have not been reported.. Binary restenosis was observed in 66 patients with 78 lesions from a total of 1,393 patients with 1,965 lesions who received follow-up angiography after SES implantation. We enrolled 55 patients with 67 lesions who underwent revascularization using another SES with a second follow-up coronary angiography. These restenotic lesions were divided into two groups based on the presence or absence of recurrent restenosis: no recurrent restenosis group (n = 56) and recurrent restenosis group (n = 11). The coronary angiography data during first and second SES implantation were compared between the groups.. Minimal lumen diameter (MLD) was smaller before first and second percutaneous coronary interventions (PCI) with SES implantation in the recurrent restenotic group compared with no recurrent restenosis group (first PCI, 0.28 ± 0.19 mm vs. 0.54 ± 0.42 mm, P = 0.040; second PCI, 0.44 ± 0.36 mm vs. 0.69 ± 0.39 mm, P = 0.036, respectively). Acute stent recoil after second SES implantation was significantly greater in the recurrent restenosis group compared with no recurrent restenosis group (0.08 ± 0.17 mm vs. 0.20 ± 0.22 mm, P = 0.049, respectively). Multivariate analysis showed preprocedural MLD at first PCI and acute stent recoil at second PCI as independent predictors of recurrent restenosis.. Preprocedural smaller MLD at first PCI and acute stent recoil at second PCI are predictors of recurrent restenosis treated on two previous occasions with SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prosthesis Design; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

To compare the outcomes between paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) for the treatment of drug-eluting stent (DES) fracture.. DES fracture is considered as an important predictor of in-stent restenosis (ISR). However, little data are available evaluating the optimal treatment for this complication of coronary stenting.. From January 1, 2004 to December 31, 2008, patients with DES ISR treated with a second DES were identified and evaluated for stent fracture. Stent fracture was defined by the presence of strut separation in multiple angiographic projections, assessed by two independent reviewers. Target lesion revascularization (TLR) at 6 and 12 months were the primary end points.. Of 131 lesions with DES ISR treated with a second DES, we found 24 patients (24 lesions, 18.2%) with angiographically confirmed stent fracture. Of these, 20 patients (20 lesions) treated with either PES (n = 11/55%) or SES (n = 9/45%) were included in the study. TLR at 6 months occurred in 9% of patients treated with PES and 22% of those treated with SES (P = 0.41). After 12 months, TLR was 9% and 55.5%, respectively (P = 0.024).. This study demonstrates a high incidence of stent fracture in patients presenting with DES ISR in need of further treatment with another DES. The suggested association between treatment of stent fracture-associated DES ISR with PES as compared with SES, and better long-term outcomes, is in need of confirmation by larger prospective registries and randomized trials.

Topics: Aged; Angioplasty, Balloon, Coronary; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Ontario; Paclitaxel; Prosthesis Design; Prosthesis Failure; Retrospective Studies; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

There have been little data regarding major determinants for the uncovered stent struts after drug-eluting stent (DES) implantation on optical coherence tomography (OCT). We investigated the major determinants of incomplete neointimal coverage of DES struts on OCT after implantation in a large cohort of patients. A total of 261 patients with 279 lesions who were treated with various DESs were selected from the OCT registry database. The lesions were divided into two groups based on the ratio of uncovered struts to total struts in all OCT cross-sections; an uncovered group (highest quartile with % uncovered struts ≥5.4%, n = 70), and covered group (the remaining lower quartiles with % uncovered struts <5.4%, n = 209). The uncovered group was more likely to have complex lesions, smaller reference vessel and stent diameter, and longer stent, more use of sirolimus-eluting stents, and less use of zotarolimus-eluting stents compared with the covered group. Of these variables, the most significant determinant of uncovered stent struts was DES type (odds ratio [OR] = 2.75, 95% confidence interval [CI] = 1.94-3.89, P < 0.001). The use of sirolimus-eluting stents (OR = 2.44, 95% CI, 1.15-5.47, P = 0.023) and zotarolimus-eluting stents (OR = 0.02, 95% CI = 0.01-0.25, P = 0.002) were the only significant risk and protective factors for uncovered stent struts, respectively. This study demonstrated that DES type might be associated with the most important determinants of uncovered struts compared to any other clinical or angiographic factor.

Topics: Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Registries; Republic of Korea; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To report the safety and efficacy of zotarolimus eluting stents for treatment of unprotected left main coronary artery disease.. Percutaneous stent insertion is an increasingly popular alternative to bypass surgery for the management of left main (LM) coronary artery disease. While data support the use of sirolimus- and paclitaxel-coated stents in the LM coronary artery, there are no published series reporting results with Endeavor (zotarolimus) stents, particularly in the context of unprotected left main (ULM) lesions.. We retrospectively identified 40 consecutive patients who had ULM disease treated with Endeavor stents (ZES) and who had follow-up angiography. The primary endpoint was the prevalence of major adverse cardiac events (MACE), including cardiac/unexplained death, nonfatal myocardial infarction (MI), and in-stent restenosis (ISR)/target lesion revascularization (TLR).. Angiographic and procedural success was achieved in all cases. Follow-up angiography occurred on average 5.6 ± 0.9 months after the index procedure. There were three incidences of ISR requiring TLR and another patient who had a NSTEMI in the follow-up period. At late follow-up (12.4 ± 1.8 months) three patients underwent CABG (one for RCA stenosis) and four patients died without knowledge of the status of the ULM stent (two cardiovascular and two deaths related to cancer progression).. In conclusion, our experience with Endeavor stents for the treatment of ULM disease demonstrates excellent angiographic and clinical outcomes, with a 7.5% ISR/TLR rate and a 15% MACE rate, respectively, at an average clinical follow-up of 12.4 months.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cause of Death; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Ontario; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Stent fracture has emerged as a complication of drug-eluting stent and is now recognized as contributing to in-stent restenosis and possibly stent thrombosis. Although optical coherence tomography (OCT) can detect stent fractures in the absence of circumference struts, it is challenging to visualize stent fractures with only cross-sectional OCT images. We describe two cases of restenosis with stent fracture detected by a novel three-dimensional OCT image reconstruction technique. This technique allows identification of a single stent fracture even in the absence of angiographic signs.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Imaging, Three-Dimensional; Male; Prosthesis Design; Prosthesis Failure; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Although several randomized trials have shown that sirolimus-eluting stent (SES) substantially reduces in-stent restenosis, recent studies have suggested the possibility of late catch-up after SES implantation. We investigated long-term angiographic outcomes after SES implantation in real-world practice.. This study was conducted on 195 patients with 253 lesions who underwent the first and long-term angiographic follow-up after SES implantation. First follow-up was done at near 6 months after SES implantation. Long-term angiographic follow-up was defined as that performed at least 36 months after index procedure. Angiographies in patients who experienced target lesion revascularization at the time of the first angiographic follow-up were excluded from the current analysis.. Minimal luminal diameter at long-term angiographic follow-up was significantly smaller compared with that at the first follow-up (2.21 ± 0.65 vs. 2.40 ± 0.55, p<0.001). In-stent late lumen loss between the first and long-term follow-up tended to be larger compared with that between SES implantation and the first follow-up (0.19 ± 0.47 vs. 0.15 ± 0.39, p=0.298). There was a trend for increased incidence of coronary artery aneurysm (1.6% and 7.5% at the first and long-term follow-up) and stent fracture (4.3% and 10.3%). Two stent aneurysms and one stent fracture were related with definite very late stent thrombosis.. An "angiographic late catch-up" phenomenon and a trend toward increased incidence of coronary artery aneurysm and stent fracture were found at a median 46.5-month angiographic follow-up compared with a median 6-month follow-up.

Topics: Coronary Aneurysm; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Sirolimus

After successful recanalization of a coronary chronic total occlusion (CTO) the risk for restenosis and subsequent need for repeat intervention is high. Everolimus-eluting stents (EESs) were associated with low rates of restenosis, reintervention and stent thrombosis in non-occluded lesions. We sought to determine the antiproliferative impact of the everolimus-eluting Xience V stent in CTOs.. Fifty-three patients with a CTO in a native coronary artery were included. CTO was defined as a duration of occlusion ≥3 months and thrombolysis in myocardial infarction 0 flow. EESs were exclusively implanted to completely cover the occluded and adjacent stenotic segments. Dual antiplatelet therapy was prescribed for 6 months. Follow-up angiography was scheduled at 6 months. Clinical follow-up was done at 12 months. The primary endpoint was late loss at the initial occlusion site. Secondary clinical endpoint was a composite of cardiac death, myocardial infarction not clearly attributable to a non-target vessel and target lesion revascularization.. Mean occlusion length was 24 ± 17 mm, ranging from 4 to 74 mm. Mean stent length was 79 ± 36 mm, ranging from 18 to 158 mm. Reference diameter was 3.27 ± 0.58 mm. Late loss at the initial occlusion site was 0.22 ± 0.69 mm. There were six (11%) binary restenosis with a target lesion reintervention in three (6%) patients. There was no death, myocardial infarction or stent thrombosis within 12 months.. In patients with successful recanalization of complex CTOs the use of EESs results in a low angiographic late loss and restenosis rate without stent thrombosis throughout 12 months follow-up.

Topics: Adult; Aged; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Sirolimus; Treatment Outcome

This study aimed to compare the neointimal coverage (NIC), subclinical thrombus, color of plaque underneath the stent at 9-month after implantation of sirolimus-eluting stent (SES) either with durable or with biodegradable polymer (BDPM).. A total of 175 patients were assigned as Cypher (n = 81, 97 stents with durable polymer) and Excel (n = 94, 112 stents with BDPM) stent at 9-month after indexed procedure. NIC was classified from grade 0-3. Color of plaque was divided into white, light-yellow, yellow, and dark yellow. Thrombus was diagnosed as white or red material with cotton-like or ragged appearance. Incomplete NIC (grade 0/1) circled by a blush was termed by "inflaming.". There were significant differences in unstable angina (90.5 vs. 52.4%, P = 0.015), previous myocardial infarction (33.3 vs. 4.0%, P = 0.045) and left ventricular eject fraction (55.2 ± 7.8 vs. 62.6 ± 6.3%, P = 0.021) between the Excel and Cypher groups. The minimal- and maximal-NIC grades in the Cypher group were 0.67 ± 0.58 and 2.29 ± 0.46, respectively, when compared with 1.45 ± 0.67 (P < 0.001) and 2.64 ± 0.49 (P = 0.023) in the Excel group. The percentage of yellow plaque, thrombus, "inflaming" and NIC grade of 0 in the Excel and Cypher groups, respectively, were as follows: 8.0 vs. 26.8% (P = 0.031), 9.8 vs. 32.9% (P = 0.024), 8.0 vs. 38.1% (P = 0.017), and 38.1 vs. 0% (P < 0.001). Of the stents with "inflaming," 63.6% had thrombus when compared with 20.1% of the non-erosion stents (P < 0.001). Overlapping segments had the lowest NIC grades and more "inflaming" demonstrating a significant difference between Cypher vs. Excel stents. NIC grade was positively correlated with thrombus.. SES with BDPM has improved NIC resulting in less yellow plaque, thrombus, and "inflaming." Overlapping segments had the lowest NIC grade and more "inflaming."

Topics: Absorbable Implants; Aged; Angioscopy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

Everolimus, a pharmaceutical component of drug-eluting stents, inhibits coronary vessel restenosis, but the antirestenotic mechanisms of action remain unclear. Here, we describe the effects of everolimus on key contributors to vessel restenosis, smooth muscle cell proliferation, and migration. In a dose-dependent fashion, everolimus reduced human coronary artery smooth muscle cell (HCASMC) proliferation without toxicity in a bimodal fashion, with accentuated potency occurring at 10 μM. Everolimus arrested the majority of HCASMCs in G1-phase, whereas it reduced the fraction of cells in S-phase at doses that inhibited DNA synthesis (bromodeoxyuridine incorporation). Consistent with this, Western blotting demonstrated that everolimus reduced activation and expression of G1-phase cell cycle progression factors, including p70S6K and cyclin D, respectively, decreased levels of proliferating cell nuclear antigen, and attenuated growth factor/serum-induced phosphorylation of the cell cycle phase transition intermediate, retinoblastoma protein. Everolimus did not, however, affect HCASMC migration. These observations suggest that everolimus acts as an antiproliferative, but not antimigratory, compound to account for at least some of the clinical efficacy exhibited by this drug as an antirestenotic agent. Moreover, everolimus-induced inhibition of the mammalian target of rapamycin complex 1 and regulation of cyclin-mediated cell cycle progression actions likely account for the antiproliferative effects of this compound on HCASMCs.

Topics: Blotting, Western; Cell Cycle; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Coronary Vessels; Cyclin D; Dose-Response Relationship, Drug; Everolimus; Humans; Immunosuppressive Agents; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes; Muscle, Smooth, Vascular; Proteins; Ribosomal Protein S6 Kinases, 70-kDa; Sirolimus; TOR Serine-Threonine Kinases

Autopsy findings have suggested delayed arterial healing as a primary cause of very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation.. Optical coherence tomography of DES-treated lesions that developed VLST (n = 6) was compared with that of DES-treated lesions that developed late in-stent restenosis (L-ISR: n = 32) among patients with recurrent ischemia >1 year after DES implantation (mean, 37 ± 17 months), and with the stented segment without any evidence of VLST or L-ISR (no-event: n = 20; mean, 38 ± 19 months). The proportion of uncovered and malapposed struts in each stented segment was evaluated. A total of 961 frames, 9,763 struts were analyzed. The proportion of uncovered struts was higher in the VLST group than in the L-ISR group and the no-event group (29.2 ± 22.8%, 7.9 ± 9.7%, and 7.6 ± 8.0%, respectively; P = 0.0002). The proportion of malapposed struts was higher in the VLST group than in the no-event group (7.3 ± 8.7% vs 1.1 ± 2.4%, P = 0.01). Two patients in the VLST group had lower rates of uncovered and malapposed struts, but this involved lipid-laden-like neointima with disruptions.. Delayed neointimal coverage and incomplete stent apposition were frequently observed in the DES-treated lesions that developed very late thrombosis. Lipid-laden-like neointima with disruption within the DES may be another possible mechanism for very late thrombosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

The authors investigate whether the combination of anti-CD34 antibody with DES is win-win cooperation.. DES may reduce the risk of restenosis compared to bare-metal stents (BMS), but they were found to inhibit the healing process of intima.. Fifteen BMS, 17 DES, and 16 combined anti-CD34 antibody and DES were randomly implanted in the coronary arteries of 22 minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary segments were examined by histological examination and scanning electron microscopy after in vivo coronary angiography and intracoronary optical coherence tomography (OCT) examinations. The other 12 minipigs were followed up to 3 months. Coronary angiography and intracoronary OCT examination were performed in vivo and histological examination was performed on the stenting coronary segments.. After 2 weeks, the neointimal covering level of the DES was lower than that in BMS, but the covering level of the combined stents was even better than the BMS. After 3 months, neointimal hyperplasia was significant in the BMS, but not in the other two types of stents. The in-stent late lumen loss of the combined stents even showed a decreasing tendency when compared with the DES.. The combination of anti-CD34 antibody and DES can not only well offset the short-term inhibitory effect on re-endothelialization but also slightly enhance the long-term antiproliferative effect.

Topics: Angioplasty, Balloon, Coronary; Animals; Antibodies; Antigens, CD34; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Hyperplasia; Metals; Microscopy, Electron, Scanning; Neointima; Prosthesis Design; Sirolimus; Stents; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Sirolimus

Topics: Angioplasty, Balloon; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Registries; Sirolimus

There is a scarcity of long-term data from large-scale drug-eluting stent registries with a large enough sample to evaluate low-frequency events such as stent thrombosis (ST).. Five-year outcomes were evaluated in 12 812 consecutive patients undergoing sirolimus-eluting stent (SES) implantation in the j-Cypher registry. Cumulative incidence of definite ST was low (30 day, 0.3%; 1 year, 0.6%; and 5 years, 1.6%). However, late and very late ST continued to occur without attenuation up to 5 years after sirolimus-eluting stent implantation (0.26%/y). Cumulative incidence of target lesion revascularization within the first year was low (7.3%). However, late target lesion revascularization beyond 1 year also continued to occur without attenuation up to 5 years (2.2%/y). Independent risk factors of ST were completely different according to the timing of ST onset, suggesting the presence of different pathophysiological mechanisms of ST according to the timing of ST onset: acute coronary syndrome and target of proximal left anterior descending coronary artery for early ST; side-branch stenting, diabetes mellitus, and end-stage renal disease with or without hemodialysis for late ST; and current smoking and total stent length >28 mm for very late ST. Independent risk factors of late target lesion revascularization beyond 1 year were generally similar to those risk factors identified for early target lesion revascularization.. Late adverse events such as very late ST and late target lesion revascularization are continuous hazards, lasting at least up to 5 years after implantation of the first-generation drug-eluting stents (sirolimus-eluting stents), which should be the targets for developing improved coronary stents.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Coronary Restenosis; Coronary Thrombosis; Death, Sudden, Cardiac; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Japan; Male; Middle Aged; Registries; Risk Factors; Sirolimus; Time Factors

This study sought to compare the 1-year safety and efficacy of Cypher Select or Cypher Select Plus (Cordis Corporation, Bridgewater, New Jersey) sirolimus-eluting stents (SES) with the treatment of bare-metal stents (BMS) and drug-eluting stent (DES) in-stent restenosis (ISR) in nonselected, real-world patients.. There is paucity of consistent data on DES for the treatment of ISR, especially, DES ISR.. The e-SELECT (Multicenter Post-Market Surveillance) registry is a Web-based, multicenter and international registry encompassing virtually all subsets of patients and lesions treated with at least 1 SES during the period from 2006 to 2008. We enrolled in this pre-specified subanalysis all patients with at least 1 clinically relevant BMS or DES ISR treated with SES. Primary endpoint was major adverse cardiac events and stent thrombosis rate at 1 year.. Of 15,147 patients enrolled, 1,590 (10.5%) presented at least 1 ISR (BMS group, n = 1,235, DES group, n = 355). Patients with DES ISR had higher incidence of diabetes (39.4% vs. 26.9%, p < 0.001), renal insufficiency (5.8% vs. 2.3%, p = 0.003), and prior coronary artery bypass graft (20.5% vs. 11.8%, p < 0.001). At 1 year, death (1.4% for BMS vs. 2.1% for DES, p = 0.3) and myocardial infarction (2.4% for BMS and 3.3% for DES, p = 0.3) rates were similar, whereas ischemia-driven target lesion revascularization and definite/probable late stent thrombosis were higher in patients with DES ISR (6.9% vs. 3.1%, p = 0.003, and 1.8% vs. 0.5%, p = 0.04, respectively).. Use of SES for either BMS or DES ISR treatment is safe and associated with low target lesion revascularization recurrence and no apparent safety concern.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Databases, Factual; Drug-Eluting Stents; Europe; Female; Health Status Indicators; Humans; Immunosuppressive Agents; Internationality; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Product Surveillance, Postmarketing; Registries; Sirolimus; Statistics as Topic

Impaired endothelial recovery after the implantation of drug-eluting stents is a major concern because of the increased risk for late stent thrombosis. The disruption of the chemokine axis CXCL12/CXCR4 inhibits neointima formation by blocking the recruitment of smooth muscle progenitor cells. To directly compare a CXCR4-targeting treatment strategy with drugs that are currently used for stent coating, we studied the effects of the CXCR4 antagonist POL5551 and the drug sirolimus on neointima formation. Apolipoprotein E-deficient mice were treated with POL5551 or sirolimus continuously for 28 days after a carotid wire injury. POL5551 inhibited neointima formation by 63% (for a dosage of 2 mg/kg/day) and by 70% (for a dosage of 20 mg/kg/day). In comparison, sirolimus reduced the neointimal area by 69%. In contrast to treatment with POL5551 during the first three days after injury, injection of POL5551 (20 mg/kg) once per day for 28 days diminished neointimal hyperplasia by 53%. An analysis of the cellular composition of the neointima showed a reduction in the relative smooth muscle cell (SMC) and macrophage content in mice that had been treated with a high dose of POL5551. In contrast, the diminished SMC content after sirolimus treatment was associated with a neointimal enrichment of macrophages. Furthermore, endothelial recovery was impaired by sirolimus, but not by POL5551. Therefore, the inhibition of CXCR4 by POL5551 is equally effective in preventing neointima formation as sirolimus, but POL5551 might be more beneficial because treatment with it results in a more stable lesion phenotype and because it does not impair re-endothelialisation.

Topics: Angioplasty; Animals; Apolipoproteins E; Blood Vessel Prosthesis Implantation; Carotid Arteries; Cell Movement; Coronary Restenosis; Disease Models, Animal; Drug-Eluting Stents; Endothelium, Vascular; Humans; Lysophospholipids; Macrophages; Mice; Mice, Knockout; Myocytes, Smooth Muscle; Neointima; Postoperative Complications; Proteins; Receptors, CXCR4; Sirolimus

Non stent based delivery of antiproliferative agents using drug coated balloon catheters may offer additional flexibility and efficacy in a broad range of applications. The lipophilic antiproliferative drug zotarolimus makes it a potential candidate for balloon delivery. The aim of the present study was to evaluate the safety and efficacy of a prototype zotarolimus coated balloon (ZCB) catheter in comparison to a zotarolimus eluting stent (ZES) in the porcine coronary overstretch model.. Eighty-four stents (diameters 3.0 and 3.5 mm; length 15 mm) were implanted in LAD and Cx of 42 domestic pigs: control (TriMaxx, Abbott, polymer coated stent without drug, implanted with uncoated PCI catheter, n = 56); ZES (ZoMaxx, Abbott, stent coated with zotarolimus in polymer, implanted with uncoated PCI catheter, n = 14); ZCB (TriMaxx, Abbott, polymer coated stent without drug, implanted with zotarolimus coated PCI catheter, n = 14). Drug content of the vessel wall (n = 9) was measured about 10-30 min post intervention with ZCB in additional pigs.. Immediately after ZCB treatment 101 ± 31 μg of zotarolimus was detected in the coronary arteries. After 28 days ZES led to a reduction of neointimal area from 4.32 ± 1.45 to 3.32 ± 1.11 mm2 (P = 0.019 vs. control). The effect of neointimal inhibition was more pronounced with the novel ZCB (2.79 ± 1.43 mm², P = 0.001 vs. control). Inflammation score was significantly reduced in vessels treated with the ZCB (0.75 ± 0.86 compared to control (1.45 ± 0.94, P = 0.013) and ZES (1.65 ± 0.90, P = 0.012).. Zotarolimus coated balloons and stents were found to effectively reduce neointimal proliferation in the porcine coronary model. Inflammation scores were significantly reduced after treatment with the coated balloon. Zotarolimus balloon coating might be a novel option in preventing and treating restenosis.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Hyperplasia; Neointima; Sirolimus; Swine

The present study evaluated the mechanism of edge restenosis after sirolimus-eluting stent (SES) implantation using serial (post-intervention and follow-up) intravascular ultrasound (IVUS) analysis.. There is little information about the mechanism of edge restenosis after SES implantation.. Serial IVUS analysis was performed at 5 mm reference segments immediately proximal and distal to the SES in 25 lesions with edge restenosis. Proximal and distal reference segments were divided into 1 mm subsegments.. Between post-intervention and follow-up IVUS studies, a decrease in external elastic membrane area was observed at the proximal edge. There was a significant increase in plaque & media area in the subsegment closest to the proximal edge. On the other hand, there was an increase in plaque & media area at the distal edge, with no change in external elastic membrane area.. There may be different mechanisms between proximal and distal edge restenosis after SES implantation. Negative remodeling plays a major role in proximal edge restenosis. On the other hand, intimal hyperplasia may mainly contribute to distal edge restenosis.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Sirolimus; Ultrasonography, Interventional

Topics: Aged; Angioplasty, Balloon; Atherectomy, Coronary; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Humans; Male; Reoperation; Sirolimus; Treatment Failure; Ultrasonography; Vascular Calcification

Thrombosis is a rare but serious complication of stent implantation in atherosclerotic arteries, affecting both bare-metal and drug-eluting stents. Diagnostic criteria for stent thrombosis have recently been updated with the time and probability of the event being considered as crucial parameters. To be considered as "definite", the diagnosis of stent thrombosis has to be confirmed by angiography or histology. This statement position has clearly rendered more difficult the clinical assessment of stent thrombosis in randomised clinical trials. Considering these limitations, stent thrombosis represents a dramatic complication for both patients and cardiologists. In coronary plaques, thrombosis is often associated with death, acute coronary syndromes and arrhythmias. For these reasons, the pharmacological improvement of this outcome represents a "hot-topic" field for research. Among several medications, statins have been shown to potentially reduce the incidence of coronary stent thrombosis in humans. However, randomised clinical trials focussing on "definite" diagnosis are still needed to confirm these promising results. In addition, the use of statins in patients implanted with stents in other arteries is largely unexplored. Finally, statin-eluting stents (only tested in pigs) have to be evaluated in other animal models and human beings. Therefore, a clear recommendation on the use of statins to prevent stent thrombosis is not available and caution should be used. The "pleiotropic" anti-atherosclerotic properties of statins might represent a crucial investigation field to pathophysiologically clarify the role of statins in stent complications.

Topics: Acute Coronary Syndrome; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Paclitaxel; Prosthesis Design; Sirolimus; Stents

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Paclitaxel; Prosthesis Failure; Sirolimus

A 52-year-old woman with Takayasu arteritis developed acute coronary syndrome and received percutaneous coronary intervention (PCI). The patient experienced restenosis three times even with drug-eluting stent (DES) implantation. We started steroid administration after the fourth PCI to reduce inflammation due to autoimmunity. With DES and a steroid combination, the patient remained free of chest pain, and a follow-up angiography demonstrated good patency of the stent site. Since in-stent restenosis may result from a complicated combination of neointimal proliferation and autoimmune mechanisms, physicians should consider a combination of DES and a steroid for the treatment of coronary artery disease in Takayasu arteritis.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Middle Aged; Neointima; Sirolimus; Steroids; Takayasu Arteritis; Tomography, X-Ray Computed

Coronary artery perforation is a rare, but particularly feared and sometimes life-threatening, complication of percutaneous coronary interventions. The incidence of coronary perforation has increased with newer, more invasive interventional devices and techniques like rotablation, excimer laser coronary angioplasty, routine high-pressure balloon dilatation, or chronic total occlusion interventions. Here we describe a case of Ellis grade 2 perforation following a balloon dilatation performed in an in-stent restenotic total occlusion. The perforation was successfully sealed with a recently introduced device, a mesh covered stent (MGuard stent, Inspire MD). This new stent is much more flexible than the polytetrafluoroethylene-covered stent, which is often implanted in Ellis 2 or 3 grade perforations.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Myocardial Infarction; Radiography; Rupture; Sirolimus; Stents; Surgical Mesh; Treatment Outcome

The current study sought to examine inflammation at the stented segments of Nobori (Terumo Corporation, Tokyo, Japan) and Cypher (Cordis, Miami, Florida) drug-eluting stents (DES), as well as free radical production and endothelial function of the adjacent nonstented segments in a pig coronary model.. Nobori is a novel DES, incorporating a biolimus A9-eluting biodegradable polymer coated only on the abluminal surface of the stent. These unique features may favorably affect inflammation and endothelial function, as compared to the currently marketed DES. Presently, pre-clinical data on direct comparison of the various generations of DES are not available.. A total of 18 DES were implanted in pig coronary arteries and subsequently explanted at 1 month. Stented segments were assessed by angiography and histology. Ex vivo vasomotor function and superoxide production in segments proximal and distal to the stent were determined. The vasoconstriction, endothelial-dependent relaxation, and endothelial-independent relaxation of proximal and distal nonstented segments were measured.. Histological evaluation revealed lower inflammatory response with Nobori than with Cypher DES. There is trend for lower angiographic percentage diameter stenosis in Nobori versus Cypher groups (p = 0.054). There was increased endothelium-dependent relaxation, decreased endothelin-1-mediated contraction, and less superoxide production in the vessel segments proximal and distal to Nobori versus Cypher stents.. Our data show significantly lower inflammatory response in the stented segments, and rapid recovery of endothelial function of peristent segments in the Nobori group compared with Cypher DES group at 1 month in porcine coronary artery model.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Dose-Response Relationship, Drug; Drug-Eluting Stents; Endothelium, Vascular; Inflammation; Japan; Models, Animal; Prosthesis Design; Recovery of Function; Sirolimus; Superoxides; Sus scrofa; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Paclitaxel; Sirolimus; Tomography, Optical Coherence; Ultrasonography, Interventional

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Paclitaxel; Sirolimus; Tomography, Optical Coherence

Biodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (Cypher™) at 28, 90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to Cypher™ at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm² vs. 3.1 ± 1.5 mm², p=0.03 and 1.8 ± 1.2 mm² vs. 3.0 ± 1.5 mm², p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drug-eluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to Cypher™ may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Lactic Acid; Models, Animal; Neointima; Polyesters; Polyglactin 910; Polymers; Prosthesis Design; Sirolimus; Sus scrofa; Time Factors; Tissue Distribution

In this study we compared the outcomes of the everolimus-eluting stent (EES) versus the zotarolimus-eluting stent (ZES) in patients treated at a tertiary medical center, with up to one year of follow-up.. Unselected consecutive patients were retrospectively recruited following stenting with the ZES (n = 197) or EES (n = 190). The first 100 consecutive patients in each cohort underwent syntax scoring. The primary endpoint of the study was target vessel failure, defined as the combined endpoint of cardiac death, non-fatal myocardial infarction, or target vessel revascularization. Secondary endpoints included target lesion revascularization, target lesion failure, acute stent thrombosis, total death, cardiac death, and non-fatal myocardial infarction.. The two groups were similar, including for Syntax scores (19.6 ± 12.8 versus 20.6 ± 13.6), number of stents per patient (2.9 ± 1.9 versus 2.9 ± 2.1), and cardiovascular risk factors. By one year, the primary outcome occurred in 20.8% EES versus 26.7% ZES (P = 0.19) patients. The secondary endpoints were as follows: target lesion revascularization (8.9% versus 20.6%, P = 0.003), target vessel revascularization (18.9% versus 25.6%, P = 0.142), definite and probable stent thrombosis (0% versus 2.5%), non-fatal myocardial infarction (2.7% versus 3.6%), and mortality (3.2% versus 5.1%) for the EES versus the ZES, respectively.. EES had similar target vessel failure to ZES, but superior target lesion revascularization and target lesion failure at one year of follow-up in an unselected cohort of patients.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Iowa; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

Drug-eluting stents (DES) have been in clinical use for nearly a decade; however, the relative short- and long-term efficacy and safety of DES compared with bare-metal stents (BMS) and among the DES types are less well defined.. PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials, until March 2012, that compared any of the Food and Drug Administration-approved durable stent and polymer DES (sirolimus-eluting stent [SES], paclitaxel-eluting stent [PES], everolimus-eluting stent [EES], zotarolimus-eluting stent [ZES], and ZES-Resolute [ZES-R]) with each other or against BMS for de novo coronary lesions, enrolling at least 100 patients and with follow-up of at least 6 months. Short-term (≤ 1 year) and long-term efficacy (target-vessel revascularization, target-lesion revascularization) and safety (death, myocardial infarction, stent thrombosis) outcomes were evaluated and trial-level data pooled by both mixed-treatment comparison and direct comparison analyses. From 76 randomized clinical trials with 117 762 patient-years of follow-up, compared with BMS, each DES reduced long-term target-vessel revascularization (39%-61%), but the magnitude varied by DES type (EES~SES~ZES-R>PES~ZES>BMS), with a >42% probability that EES had the lowest target-vessel revascularization rate. There was no increase in the risk of any long-term safety outcomes, including stent thrombosis, with any DES (versus BMS). In addition, there was reduction in myocardial infarction (all DES except PES versus BMS) and stent thrombosis (with EES versus BMS: Rate ratio, 0.51; 95% credibility interval, 0.35-0.73). The safest DES appeared to be EES (>86% probability), with reduction in myocardial infarction and stent thrombosis compared with BMS. Short-term outcomes were similar to long-term outcomes, with SES, ZES-R, and everolimus-eluting stent being the most efficacious and EES being the safest stent.. DES are highly efficacious at reducing the risk of target-vessel revascularization without an increase in any safety outcomes, including stent thrombosis. However, among the DES types, there were considerable differences, such that EES, SES, and ZES-R were the most efficacious and EES was the safest stent.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Metals; Middle Aged; Paclitaxel; Randomized Controlled Trials as Topic; Registries; Risk Factors; Sirolimus; Time; Treatment Outcome; Tubulin Modulators

Several reports have shown contrary results regarding the efficacy of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in diabetic patients. The association between hemoglobin A1c (A1c) before coronary intervention and the midterm clinical outcomes of patients treated with these stents is unclear. The enrolled population was 415 patients with diabetes or impaired glucose tolerance (IGT) who underwent follow-up angiography after being implanted with a SES (n = 282) or PES (n = 133). The enrolled population was classified into the optimal glycemic control group (n = 213) and suboptimal glycemic control group (n = 202), and the predictors of restenosis were examined in each group. In the optimal glycemic control group, the use of PES was an independent predictor of restenosis [odds ratio (OR) 9.98, 95% confidence interval (CI) 3.08-38.9, p < 0.0001]; on the other hand, the use of SES was a positive independent predictor of restenosis prevention (OR 0.10, 95% CI 0.03-0.32, p < 0.0001). In the suboptimal glycemic control group, neither stent was predictive of restenosis. In a subanalysis, preprocedural A1c (≥7.0%) was found to be an independent predictor of restenosis in the SES group (OR 3.61, 95% CI 1.14-12.8, p = 0.03), but not the PES group. Postprocedural A1c (≥7.0%) was not an independent predictor of restenosis in either stent group. This study showed that the superiority of SES compared to PES was attenuated in the suboptimal glycemic control group. Preprocedural A1c (≥7.0%) was found to be an independent predictor of restenosis in the SES group, but not in the PES group.

Topics: Aged; Aged, 80 and over; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Female; Glycated Hemoglobin; Humans; Male; Paclitaxel; Percutaneous Coronary Intervention; Retrospective Studies; Sirolimus; Treatment Outcome

Delayed endothelialization contributes to stent thrombosis of current drug-eluting stents. The asymmetrical coating technique provides an anti-proliferative effect abluminally without affecting luminal endothelialization. Layer-by-layer self-assembled chitosan/heparin (C/H LBL) has been proved to promote re-endothelialization. A novel stent system, C/H LBL coated luminally and sirolimus released abluminally (C/H LBL-SES), was fabricated.. Bare metal stents (BMS), traditionally circumferential sirolimus-eluting stents (SES), and C/H LBL-SES were implanted into porcine coronary arteries. At the 7, 14 and 28 days follow-up (FU), angiography, intravascular ultrasound (IVUS), vasomotor function induced by acetylcholine (Ach), scanning-electron microscopy and histopathology were performed. Remodeling index (RI) was based on IVUS and defined as cross-sectional area (CSA) of vessel at in-stent segment divided by CSA of reference vessel and expressed as a percentage with a normal range from 0.95 to 1.05.. Thirty-eight mini pigs were enrolled and 74 stents (BMS = 23, C/H LBL = 28, SES = 23) were implanted in this study. At 28 days after implantation, the diameter stenosis of C/H LBL-SES by quantitative coronary angiography was 18.8 ± 2.5 %, the area stenosis by histomorphometry was 24.2 ± 2.9 %, which were comparable to that of SES and superior to BMS. At 14 days, re-endothelialization of C/H LBL-SES was almost completed, while only about 50 % of surface of SES was covered by endothelium. At 7, 14 and 28 days FU, although C/H LBL-SES suffered a greater vasoconstriction induced by Ach infusion than BMS (P < 0.05), it behaved better than SES (P < 0.01). No sign of stent malapposition was detected, while RI was within the normal range by IVUS. No acute or subacute thrombotic events occurred in all three groups.. The asymmetrically designed C/H LBL-SES successfully inhibited neointima hyperplasia, while diminishing vasoconstriction after Ach-stress. Endothelialization of C/H LBL-SES was less affected compared with traditionally circumferentially coated SES.

Topics: Acetylcholine; Animals; Cardiovascular Agents; Chitosan; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Heparin; Hyperplasia; Metals; Microscopy, Electron, Scanning; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Swine, Miniature; Time Factors; Ultrasonography, Interventional; Vasoconstriction

To evaluate the safety and efficacy of unrestricted Endeavor Resolute zotarolimus-eluting stent (ZES) use. Furthermore, we sought to evaluate clinical outcomes associated with on- and off-label use of Resolute ZES.. The current study was a prospective, single-center registry. The primary endpoint was major adverse cardiac events (MACE), defined as the composite of death, myocardial infarction (MI), and target-vessel revascularization (TVR). Secondary endpoints were death, MI, TVR, and stent thrombosis (ST).. A total of 370 patients were prospectively enrolled. Off-label Resolute ZES use was performed in 311 patients (84%). At a mean follow-up of 17.3 ± 6 months, MACE occurred in 31 patients (8.5%), death in 15 (4.1%), MI in 10 (2.7%), and TVR in 19 (5.2%). Definite, probable, and possible ST occurred in 9 patients (2.5%). Off-label Resolute ZES implantation, as compared to on-label use, was not associated with an increased risk of MACE (9.4% vs 3.4%; P=.13), death (4.9% vs 0%; P=.14), MI (3.3% vs 0%; P=.38), and TVR (5.5% vs 3.4%; P=.75). On multivariable analysis, previous revascularization (P=.008), but not off-label Resolute ZES implantation (P=.07), was associated with MACE.. In daily clinical practice, Resolute ZES was mostly implanted in patients with off-label indications and associated with a relatively low rate of MACE and TVR.

Topics: Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Logistic Models; Male; Multivariate Analysis; Off-Label Use; Prospective Studies; Prosthesis Failure; Registries; Risk Assessment; Sirolimus; Statistics, Nonparametric; Survival Rate; Treatment Outcome

Gender-related differences in long-term outcomes of patients receiving the Endeavor zotarolimus-eluting stent (ZES) (Medtronic) have not been well defined. In this study, we evaluate the differences between men (M) and women (W) for 2-year target vessel failure (TVF) in an unselected consecutive series of patients treated with the ZES at our institution.. Data on 197 consecutive patients (133 M, 64 W) stented with the ZES were retrospectively analyzed. The primary endpoint of the study was to compare gender-related outcomes in TVF, defined as the combined endpoint of cardiac death, non-fatal myocardial infarction, and target vessel revascularization (TVR). Secondary endpoints included TLR, TVR, acute stent thrombosis (ST) as defined by the academic research consortium (ARC), and cardiac death. The cine angiograms of the first consecutive 122 patients (79 M, 43 W) were independently reviewed by a cardiologist blinded to clinical outcome and SYNTAX scoring was performed. Follow-up was achieved using medical records and/or phone calls and was censored at 730 days. Descriptive analysis was performed on all variables. Univariate analysis compared the M and W cohorts. Logistic regression analysis modeling for predictors of TVF was performed and survival analysis between the 2 groups was plotted.. The 2 groups were well matched for demographic, clinical, angiographic, and procedural variables. Angiographic complexity was also statistically similar between the 2 groups as judged by SYNTAX scoring (15.8 ± 10.9 M vs 13.5 ± 8.3 W; P=.197). At 2-year follow-up, TVF was 22.6% and 32.8% (P=.684) with no statistical difference between TLR (18.1% M vs 12.8% W), TVR (21.8% M vs 32.8% W), cardiac death (2.3% M vs 6.3% W), and definite and probable stent thrombosis (2.26% M vs 3.13% W). Logistic regression analyses modeling for age, gender, New York Heart Association (NYHA) class, non-left main (LM) bifurcation lesions, ostial lesions, trifurcating LM, and pre-percutaneous coronary intervention (PCI) lesion severity showed that a higher NYHA class (odds ratio [OR], 2.68; P=.005), ostial lesions (OR, 5.68; P<.001), bifurcating non-LM lesions (OR, 2.74; P=.015), and trifurcating LM lesions (OR, 28.24; P<.001) predicted a higher TVF. Female gender (P=.086) and age (P=.09) were not independent predictors of TVF.. In this cohort of patients receiving ZES, men and women had similar outcomes at 2-year follow-up consistent with recent reports in the current era of PCI. Complex coronary anatomy (ostial, non-LM bifurcations, and LM trifurcations) and advanced heart failure were stronger predictors of higher TVF than gender and age.

Topics: Academic Medical Centers; Aged; Aged, 80 and over; Analysis of Variance; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prosthesis Failure; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Sirolimus; Survival Rate; Treatment Outcome

Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes.. Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M-10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours.. After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥ 10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect.. After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients.

Topics: Animals; Apoptosis; Cardiovascular Agents; Cells, Cultured; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Endothelial Cells; Everolimus; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Necrosis; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Time Factors; Wound Healing

The purpose of the present study was to examine the mid-term clinical and angiographic outcomes of patients with ST-segment elevation myocardial infarction (STEMI) who presented within 48 h and received paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES).. This study was a retrospective, non-randomized, single-center study. The post-discharge clinical outcomes of 357 consecutive patients who presented within 48 h of their first STEMI and received PES (n=163) or SES (n=194) between February 2007 and February 2009 were analyzed in May 2011. The incidence of post-discharge events (i.e. cardiac death and non-fatal recurrent MI) after PES placement (0.6%) did not significantly differ from that after SES placement (1.5%). Treatment with PES was not related to the risk of adverse events post-discharge (mean follow-up period for PES placement, 1170±243 days; hazard ratio, 0.346; 95% CI, 0.036-3.371; p=0.361). No definite stent thromboses developed after treatment with PES or SES. The incidence of binary in-stent restenosis (stenosis of more than 50% of the diameter at secondary angiography performed 10-18 months after the initial procedure) after PES placement (17.1%) was significantly higher than that after SES placement (4.8%; p<0.001). PES placement was an independent predictor of binary in-stent restenosis (odds ratio, 3.892; 95% CI, 1.470-10.30; p=0.006).. Retrospective examination of the post-discharge clinical course after placement of PES and SES showed favorable midterm clinical outcomes among Japanese STEMI patients treated within 48h of onset. However, SES treatment resulted in superior angiographic outcomes compared to PES.

Topics: Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

The ideal bifurcation stenting technique is not established, and data on the hemodynamic characteristics at stented bifurcations are limited.. We used computational fluid dynamics analysis to assess hemodynamic parameters known affect the risk of restenosis and thrombosis at coronary bifurcations after the use of various single- and double-stenting techniques. We assessed the distributions and surface integrals of the time averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (t(r)). Single main branch stenting without side branch balloon angioplasty or stenting provided the most favorable hemodynamic results (integrated values of TAWSS=4.13·10(-4) N, OSI=7.52·10(-6) m(2), t(r)=5.57·10(-4) m(2)/Pa) with bifurcational area subjected to OSI values >0.25, >0.35, and >0.45 calculated as 0.36 mm(2), 0.04 mm(2), and 0 mm(2), respectively. Extended bifurcation areas subjected to these OSI values were seen after T-stenting: 0.61 mm(2), 0.18 mm(2), and 0.02 mm(2), respectively. Among the considered double-stenting techniques, crush stenting (integrated values of TAWSS=1.18·10(-4) N, OSI=7.75·10(-6) m(2), t(r)=6.16·10(-4) m(2)/Pa) gave the most favorable results compared with T-stenting (TAWSS=0.78·10(-4) N, OSI=10.40·10(-6) m(2), t(r)=6.87·10(-4) m(2)/Pa) or the culotte technique (TAWSS=1.30· 10(-4) N, OSI=9.87·10(-6) m(2), t(r)=8.78·10(-4) m(2)/Pa).. In the studied models of computer simulations, stenting of the main branch with our without balloon angioplasty of the side branch offers hemodynamic advantages over double stenting. When double stenting is considered, the crush technique with the use of a thin-strut stent may result in improved immediate hemodynamics compared with culotte or T-stenting.

Topics: Angioplasty, Balloon, Coronary; Computer Simulation; Coronary Artery Disease; Coronary Circulation; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Humans; Hydrodynamics; Immunosuppressive Agents; Models, Cardiovascular; Risk Factors; Sirolimus

Peri-stent contrast staining (PSS) is an abnormal angiographic finding following drug-eluting stent implantation which suggests the presence of a space outside the stent struts. PSS has been reported to be associated with very late stent thrombosis (VLST). The aims of this study were to compare the occurrence rate of late acquired PSS between sirolimus-eluting stent (SES) and everolimus-eluting stent (EES) implantation, and to identify clinical characteristics associated with PSS. The percutaneous coronary intervention (PCI) database of our hospital was queried to identify patients meeting the following criteria: (i) patients who received SES or EES in de novo coronary artery lesions; and (ii) patients who had angiographic follow-up between 3 and 15 months after stent implantation. There were 221 patients with 249 lesions treated with SES, and 173 patients with 212 lesions treated with EES. The occurrence of PSS was evaluated and compared between SES and EES implantation on a patient and lesion basis. The occurrence rate of late acquired PSS with EES was lower than that with SES. (On a patient basis; 1.2% versus 4.5%, P = 0.045, on a lesion basis; 0.9% versus 4.0%, P = 0.043). Among the clinical characteristics, chronic total occlusion (CTO) lesions were associated with PSS. The occurrence of late acquired PSS in EES was lower than that in SES. In conclusion, the occurrence rate of late acquired PSS with EES was lower than that with SES, however, it remains to be determined whether this difference translates to the difference in the rate of VLST.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Everolimus; Extravasation of Diagnostic and Therapeutic Materials; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Risk Factors; Sirolimus; Stents

SPIRIT Women is the first interventional trial dedicated exclusively to women, focusing on symptoms at presentation, referral time to coronary intervention and the safety and performance of the XIENCE V stent.. SPIRIT Women is a prospective, open-label, multicentre study in which 1,573 women were enrolled at 73 sites outside the United States. The primary endpoint is the composite of all death, Academic Research Consortium (ARC) defined myocardial infarction (MI) and target vessel revascularisation (TVR) at one year. Data collected included symptoms at presentation and referral to coronary intervention. To allow comparison by gender, the latter were compared to data from male patients from the SPIRIT V study. The one- and two-year composite of all death, MI and TVR was 12% and 15%, respectively. Target lesion revascularisation (TLR) and stent thrombosis (definite and probable) rates were 2.4% and 0.59%, respectively, at one year and 3.6% and 0.73%, at two years. The total referral time for coronary intervention in women was four days longer than for men in the SPIRIT V study.. The XIENCE V stent is safe and effective with low TLR and stent thrombosis rates. More efforts remain to be made to increase the awareness of women and physicians of the risk for coronary artery disease (CAD).

Topics: Adolescent; Adult; Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Prospective Studies; Referral and Consultation; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The aim of this study was to evaluate the 5-year clinical outcomes of patients who underwent sirolimus-eluting stent implantation for chronic total occlusion (CTO). Among 10,759 patients treated exclusively with sirolimus-eluting stent in the j-Cypher registry, clinical outcomes were compared between 1,210 patients with revascularization for CTO and 9,549 patients with revascularization for non-CTO only. The cumulative 5-year incidence of all-cause death (13.2% vs 14.3%, p = 0.56) and definite stent thrombosis (1.9% vs 1.6%, p = 0.76) was similar between the 2 groups. The adjusted risk for CTO relative to non-CTO for all-cause death and definite stent thrombosis was insignificant (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.81 to 1.16, and HR 0.99, 95% CI 0.6 to 1.65, respectively). The cumulative incidence of target lesion revascularization was significantly higher in the CTO group (20.7% vs 14.8%, p <0.001). The adjusted risk for target lesion revascularization was significant (HR 1.31, 95% CI 1.13 to 1.52, p <0.001). In the subgroup analysis, the risk for CTO for all-cause death tended to be lower in the subgroup of patients with left ventricular ejection fractions ≤40% (HR 0.68, 95% CI 0.45 to 1.01, p = 0.053), while the risk was significantly higher in the subgroup of patients with end-stage renal disease without hemodialysis (HR 1.66, 95% CI 1.02 to 2.70, p = 0.04). In conclusion, sirolimus-eluting stent implantation for CTO appears to be as safe as that for non-CTO for up to 5 years, except for the modestly elevated risk for target lesion revascularization and the higher risk for all-cause death in patients with end-stage renal disease without hemodialysis.

Topics: Aged; Angioplasty, Balloon, Coronary; Cause of Death; Chronic Disease; Cohort Studies; Confidence Intervals; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Safety; Prognosis; Registries; Retreatment; Risk Assessment; Severity of Illness Index; Sirolimus; Survival Analysis; Time Factors; Treatment Outcome