sirolimus and Myocardial-Ischemia

Drug-eluting stent (DES) use has increased greatly as a result of early trial evidence of a reduction in restenosis. However, thet are expensive and do not improve patient survival. Therefore their use has been rationed in some countries. There is a paucity of clinical evidence for some patient groups such as non-ST elevation myocardial infarction and multi-vessel disease. Recent studies suggest that the early benefits of drug-eluting stents may be offset by an increased risk in late stent thrombosis which is a potentially fatal complication. However, the absolute risk appears low and, as yet, there is no evidence of an increased risk of stent-thrombosis related myocardial infarction or death in patients studied in randomised clinical trials. Long-term use of anti-platelet therapy may protect against the risk of late stent thrombosis but the optimal treatment strategy is currently unclear. The aim of this paper is to provide an up-to-date review of the current evidence on DES; including clinical effectiveness, the limitations of existing trials, the emerging evidence on late stent thrombosis and the potential role of clopidogrel.

Topics: Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Myocardial Ischemia; Paclitaxel; Platelet Aggregation Inhibitors; Sirolimus; Stents; Treatment Outcome; Tubulin Modulators

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

It is very well known that the development of medical disciplines, but also nonmedical sciences such as ethics, physics, or economy has a remarkable impact on advances in transplantology. A question arises whether transplantology gives anything in return? Presented paper provides several examples of how transplantation contributes to the world of medicine. These examples include influence of both clinical practice and research in the field of transplantation on the advances in other medical specializations: nephrology (treatment of glomerulopathies, reducing fibrosis), cardiology (preventing atherosclerosis and neointima formation, sirolimus-coated stents), haematology (Sirolimus for GvHD) or oncology (anti-tumor effects of sirolimus).

Topics: Coated Materials, Biocompatible; Humans; Immunosuppressive Agents; Medicine; Myocardial Ischemia; Science; Sirolimus; Stents; Transplantation

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

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

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

To investigate the impact of different anti-platelet strategies on outcomes after percutaneous coronary intervention (PCI) in patients with established cardiovascular disease (CVD).. GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing one-month dual anti-platelet therapy (DAPT) with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. Established CVD was defined as ≥1 prior myocardial infarction, PCI, coronary artery bypass operation, stroke, or established peripheral vascular disease. The primary endpoint was a composite of all-cause death or new Q-wave MI at 2-years. The secondary safety endpoint was BARC 3 or 5 bleeding. Exploratory secondary endpoints were the patient-orientated composite endpoint and net adverse clinical events.. Among the 15,761 patients in this cohort were 6,693 patients (42.5%) with established CVD. Compared to those without established CVD, these patients had significantly higher rates of the primary (5.1 vs. 3.3%, HR1.59[1.36-1.86], p < .001) and secondary composite endpoints with no significant differences in bleeding. There was a nonsignificant reduction in the primary endpoint in patients with established CVD receiving the experimental treatment (4.6 vs. 5.6%, HR0.82[0.66-1.02], p = .07). When comparing patients without CVD to those with one or three territories of CVD, the hazard ratio for the primary endpoint increased in unadjusted and adjusted models.. The poorer outcomes in patients with established CVD are not mitigated by prolonged monotherapy with a potent P2Y12 inhibitor suggesting a greater need to focus on modifiable risk factors.

Topics: Aged; Aspirin; Drug Administration Schedule; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Heart Disease Risk Factors; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Assessment; Sirolimus; Ticagrelor; Time Factors; 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

There is limited data comparing the Xience everolimus-eluting stent (EES) and the Resolute zotarolimus-eluting stent (ZES) with the BioMatrix biolimus-eluting stent (BES).. This open-label, randomized, noninferiority trial enrolled all-comer patients to be randomly treated with either BES, EES, or ZES in a 1:1:1 ratio in 15 centers across South Korea. The primary end point was a device-oriented composite outcome consisting of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization at 24 months. The BES was compared with the EES and the ZES by intention-to-treat analyses with a noninferiority margin of 3.8%, respectively.. Because of slow recruitment and low event rates, this trial was prematurely terminated after enrollment of 1935 (75%) of the intended 2580 patients. Of the 1911 patients randomized to either EES (n=638), BES (n=634), or ZES (n =639), the rate of device-oriented composite outcome was 3.6%, 2.2%, and 3.9%, respectively, at 24 months (BES versus EES: absolute risk difference -1.4% [upper limit of 1-sided 95% CI: -3.2%];. The BES was noninferior to either the EES or the ZES in all-comer patients for device-oriented composite outcome at the 24-month follow-up. However, caution is advised regarding interpretation of these results due to the premature termination of this study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01397175.

Topics: Aged; Cardiovascular Agents; Drug-Eluting Stents; Early Termination of Clinical Trials; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Prosthesis Design; Recurrence; Republic of Korea; Risk Factors; Sirolimus; Treatment Outcome

The impact of coronary artery disease (CAD) extension/complexity on outcomes and on the comparative benefits/risks of zotarolimus-eluting stent (ZES) versus bare-metal stents (BMS) remains unclear in patients at high risk of bleeding or thrombosis or at low restenosis risk.. We performed a post-hoc analysis of the ZEUS trial. The impact of coronary anatomic complexity measured by the SYNTAX score on the differences in outcomes following ZES and BMS was assessed at 1 year.. The mean SYNTAX score was 16.3 ± 13.1 with a median of 12 (IQR: 7 to 22). We stratified patients according to SYNTAX tertiles (0-8: n = 563; >8-19 n = 532; >19: n = 511), and observed that the higher the score, the correspondingly higher was the rate of the primary endpoint of major adverse cardiovascular events (MACE) and other ischemic events, but not bleeding after adjustment. The superior efficacy of ZES versus BMS for MACE was consistent across SYNTAX tertiles (tertile 1: HR 0.71, 95% CI 0.44-1.13; tertile 2: HR 0.71, 95% CI 0.46-1.09; tertile 3: HR 0.83, 95% CI 0.61-1.10) without significant heterogeneity (p for trend = 0.55). This between-groups difference mainly reflected a reduction in MI and TVR without effect on mortality. There was no significant interaction between the SYNTAX score and allocated stent type with respect to ischemic and bleeding endpoints.. The SYNTAX score was predictor of major adverse cardiovascular events but not bleeding and ZES provided superior efficacy and safety than BMS across the whole spectrum of CAD complexity. SYNTAX score may be routinely used for the assessment of the ischemic risk (but not bleeding) after PCI and should not guide the decision-making for DES versus BMS in patients undergoing PCI.

Topics: Aged; Aged, 80 and over; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Female; Hemorrhage; Humans; Internationality; Male; Myocardial Ischemia; Percutaneous Coronary Intervention; Risk Factors; Single-Blind Method; Sirolimus; Stents; Treatment Outcome

The FIREHAWK is a drug-eluting stent with a fully biodegradable sirolimus-containing polymer coating localised to recessed abluminal grooves on the stent surface. We investigated clinical outcomes with this targeted, low-dose, biodegradable polymer, sirolimus-eluting stent compared with XIENCE durable polymer, everolimus-eluting stents in an all-comers population.. The TARGET All Comers study was a prospective, multicentre, open-label randomised non-inferiority trial done at 21 centres in ten European countries. Patients with symptomatic or asymptomatic coronary artery disease and objective evidence of myocardial ischaemia who qualified for percutaneous coronary intervention were randomised 1:1 to undergo implantation of a FIREHAWK or XIENCE. Randomisation was web-based, with random block allocation and stratification by centre and ST elevation myocardial infarction. Outcome assessors were masked to treatment allocation, but treating physicians and patients were not. The primary endpoint was target lesion failure at 12 months, a composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation. The control event rate for XIENCE was assumed to be 7%, the non-inferiority margin was 3.5%, and the primary analysis was in the intention-to-treat population, censoring patients who did not have either an event before 365 days or contact beyond 365 days. Late lumen loss was the primary endpoint of an angiographic substudy designed to investigate the non-inferiority of the FIREHAWK compared with the XIENCE stent. This trial is registered with ClinicalTrials.gov, number NCT02520180.. In a broad all-comers population of patients requiring stent implantation for myocardial ischaemia, the FIREHAWK was non-inferior to the XIENCE as assessed with the primary endpoint of target lesion failure at 12 months and in-stent late lumen loss at 13 months. The FIREHAWK is a safe and effective alternative stent to treat patients with ischaemic coronary artery disease in clinical practice.. Shanghai Microport Medical.

Topics: Absorbable Implants; Aged; Drug-Eluting Stents; Equivalence Trials as Topic; Everolimus; Female; Humans; Immunosuppressive Agents; Intention to Treat Analysis; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Prosthesis Design; Sirolimus; Treatment Outcome

Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent. Here we report secondary clinical and procedural outcomes after 1 year of follow-up.. In a single-blind, multicentre, randomised trial, we enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb, Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience, Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. The co-primary endpoints of this study are vasomotion (change in mean lumen diameter before and after nitrate administration at 3 years) and difference between minimum lumen diameter (after nitrate administration) after the index procedure and at 3 years. Secondary endpoints were procedural performance assessed by quantitative angiography and intravascular ultrasound; composite clinical endpoints based on death, myocardial infarction, and coronary revascularisation; device and procedural success; and angina status assessed by the Seattle Angina Questionnaire and exercise testing at 6 and 12 months. Cumulative angina rate based on adverse event reporting was analysed post hoc. This trial is registered at ClinicalTrials.gov, number NCT01425281.. Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the bioresorbable scaffold group (335 patients, 364 lesions) or the metallic stent group (166 patients, 182 lesions). Dilatation pressure and balloon diameter at the highest pressure during implantation or postdilatation were higher and larger in the metallic stent group, whereas the acute recoil post implantation was similar (0.19 mm for both, p=0.85). Acute lumen gain was lower for the bioresorbable scaffold by quantitative coronary angiography (1.15 mm vs 1.46 mm, p<0.0001) and quantitative intravascular ultrasound (2.85 mm(2)vs 3.60 mm(2), p<0.0001), resulting in a smaller lumen diameter or area post procedure. At 1 year, however, cumulative rates of first new or worsening angina from adverse event reporting were lower (72 patients [22%] in the bioresorbable scaffold group vs 50 [30%] in the metallic stent group, p=0.04), whereas performance during maximum exercise and angina status by SAQ were similar. The 1-year composite device orientated endpoint was similar between the bioresorbable scaffold and metallic stent groups (16 patients [5%] vs five patients [3%], p=0.35). Three patients in the bioresorbable scaffold group had definite or probable scaffold thromboses (one definite acute, one definite sub-acute, and one probable late), compared with no patients in the metallic stent group. There were 17 (5%) major cardiac adverse events in the bioresorbable scaffold group compared with five (3%) events in the metallic stent group, with the most common adverse events being myocardial infarction (15 cases [4%] vs two cases [1%], respectively) and clinically indicated target-lesion revascularisation (four cases [1%] vs three cases [2%], respectively).. The everolimus-eluting bioresorbable scaffold showed similar 1-year composite secondary clinical outcomes to the everolimus-eluting metallic stent.. Abbott Vascular.

Topics: Absorbable Implants; Adolescent; Adult; Aged; Aged, 80 and over; Biocompatible Materials; Coronary Angiography; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Quality of Life; Single-Blind Method; Sirolimus; Surveys and Questionnaires; Tissue Scaffolds; Treatment Outcome; Young Adult

New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent.. This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All patients who presented with stable coronary artery disease or acute coronary syndromes and at least one coronary artery lesion (more than 50% stenosis) from March, 2011, to August, 2012, were assessed for eligibility. Patients were randomly assigned in a 1:1 ratio to receive either the durable-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat. The trial was powered to assess non-inferiority of durable-polymer zotarolimus-eluting stent compared with the biodegradable-polymer biolimus-eluting stent with a predetermined non-inferiority margin of 0·025. This trial is registered with ClinicalTrials.gov, number NCT01956448.. Of 7103 screened, 1502 patients with 1883 lesions were assigned to receive the durable-polymer zotarolimus-eluting stent and 1497 patients with 1791 lesions to receive the biodegradable-polymer biolimus-eluting stent. 79 (5·3%) and 75 (5·0%) patients, respectively, met the primary endpoint (absolute risk difference 0·0025, upper limit of one-sided 95% CI 0·016%; p=0·004). The individual components of the primary endpoint did not differ significantly between stent types at 12 months.. The durable-polymer-coated zotarolimus-eluting stent was non-inferior to the biodegradable-polymer-coated biolimus-eluting stent in unselected patients.. Medtronic Cardiovascular and Biosensors Interventional Technologies.

Topics: Absorbable Implants; Aged; Coated Materials, Biocompatible; Denmark; Drug-Eluting Stents; Equipment Design; Female; Humans; Immunosuppressive Agents; Intention to Treat Analysis; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Polymers; Sirolimus; Treatment Outcome

The aim of this study was to establish safety and efficacy of a new sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES). Sirolimus-eluting stent with bioresorbable polymer was compared with everolimus-eluting, permanent polymer, Xience stent (PP-EES) in the frame of a CENTURY II clinical trial designed to make global clinical data compliant with regulatory requirements in Europe and Japan.. The CENTURY II is a prospective, multicentre, randomized (1 : 1), single blind, controlled, non-inferiority clinical trial conducted at 58 study sites in Japan, Europe, and Korea. A total of 1123 patients requiring a percutaneous coronary intervention (PCI) procedure, with implantation of drug-eluting stent (DES), were enrolled [total population (TP)]. Randomization of patients was stratified for the subset of patients matching requirements for DES in Japan (Cohort JR, n = 722). Baseline patient demographic and angiographic characteristics were similar in both study arms, with minimal differences between the TP and Cohort JR. The primary endpoint, freedom from target lesion failure (TLF) at 9 months-TLF [composite of cardiac death, target-vessel-related myocardial infarction (MI) and target lesion revascularization]-was 95.6% with BP-SES and 95.1% with PP-EES (Pnon-inferiority<0.0001). Composite of cardiac death and MI rate was 2.9 and 3.8% (P = 0.40) and target vessel revascularization was 4.5% with BP-SES and 4.2% with PP-EES (P = 0.77). The stent thrombosis rate was 0.9% in both arms. In Cohort JR, freedom from TLF was 95.9 and 94.6% (Pnon-inferiority < 0.0005) with BP-SES and PP-EES, respectively.. The new bioresorbable polymer sirolimus-eluting stent showed safety and efficacy profiles similar to durable polymer everolimus-eluting stent at 9-month follow-up.. UMIN000006940.

Topics: Absorbable Implants; Aged; Coronary Angiography; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Myocardial Ischemia; Percutaneous Coronary Intervention; Prospective Studies; Single-Blind Method; Sirolimus; Treatment Outcome

Few multicenter studies have assessed the effects of angiotensin receptor blockers on cardiovascular events after drug-eluting stent implantation in patients with ischemic heart disease.. An open-label multicenter randomized prospective study is in progress to evaluate the effects of candesartan on cardiovascular events in patients with ischemic heart disease after implantation of sirolimus- and/or paclitaxel-eluting stents.. A total of 1,145 patients were enrolled at 39 institutes in the Candesartan for prevention of Cardiovascular events after CYPHER or TAXUS Coronary stenting (4C trial). Patients were randomized into a group treated with candesartan (n=602) and a group treated with standard medical therapy without candesartan (n=543). The primary endpoint of the 4C trial is a composite of all-cause death, successful resuscitation after cardiopulmonary arrest and cardiovascular events including non-fatal myocardial infarction, unstable angina requiring emergent hospitalization, congestive heart failure requiring emergent hospitalization and cerebrovascular attacks. All patients will be followed-up for 36 months.. The 4C trial will be the first multicenter study to elucidate the effects of candesartan after drug-eluting stent implantation and may provide new information to optimize medical therapy after percutaneous coronary interventions.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Cardiovascular Diseases; Clinical Protocols; Combined Modality Therapy; Drug Discovery; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Sirolimus; Tetrazoles

The BASE-ACS trial demonstrated an outcome of the titanium-nitride-oxide-coated bioactive stents (BAS) statistically non-inferior to that of the everolimus-eluting stents (EES) at 12-month follow-up in patients presenting with acute coronary syndrome (ACS). We performed a post hoc analysis of the BASE-ACS trial with particular focus on stent-oriented versus patient-oriented outcome at 24-month follow-up.. A total of 827 patients with ACS were randomly assigned to receive either BAS (417) or EES (410). Stent-oriented outcome was defined as a composite of cardiac death, target vessel-related non-fatal myocardial infarction, or ischemia-driven target lesion revascularization. Patient-oriented outcome was defined as a composite of all-cause death, any non-fatal myocardial infarction, or any revascularization.. Clinical follow-up for 24 months was completed in 406 (97.4%) patients in the BAS group and in 398 (97.1%) in the EES group. Stent-oriented outcome at 24-month follow-up occurred at similar frequencies in the two stent groups (10.1% for BAS versus 11.2% for EES, P=0.53). Likewise, patient-oriented outcome at 24-month follow-up was similar in the two groups (16.3% versus 19.8%, respectively, P=0.2).. In patients presenting with ACS, the rates of both stent-oriented and patient-oriented outcomes at 24-month follow-up in the BAS group were similar to those in the EES group.

Topics: Acute Coronary Syndrome; Aged; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Patient Outcome Assessment; Percutaneous Coronary Intervention; Prospective Studies; Single-Blind Method; Sirolimus; Stents; Titanium; Treatment Outcome

In the treatment of bifurcation lesions, routine stenting of both branches has thus far failed to demonstrate a clear clinical advantage over a provisional one-stent strategy. On the other hand, large scale data evaluating different stent types for clinical outcomes after one-stent treatment with final kissing inflation (FKI) of bifurcation lesions is also limited. This prospective study evaluated the clinical and angiographic outcomes of paclitaxel-eluting stents (PES) vs. sirolimus-eluting stents (SES) in single crossover main branch stenting followed by FKI in patients with bifurcation lesions.. We randomized 800 patients with single bifurcation lesions to PES (n=400) and SES (n=400) groups.. Crossover rates to the two-stent strategy were low in both groups (PES 1.5%, SES 2.8%; p=0.23). At 1 year, there was no significant difference in the primary endpoint of this study, target lesion revascularization rate (PES 3.8%, SES 3.2%, hazard ratio 0.83; 95% confidence interval 0.39 to 1.76; p=0.62). Stent thrombosis occurred in only 1 case in the SES group after 282 days. At 9 months, a total of 593 patients underwent quantitative coronary measurement. The main branch restenosis rate in the PES group was significantly higher than that of the SES group (PES 12.2%, SES 5.5%; p=0.004), however both groups exhibited similar high side branch restenosis rates (PES 17.2%, SES 19.3%; p=0.6).. In patients with bifurcation lesions, a single stent strategy using PES and SES with FKI indicated similar 1 year clinical outcomes and safety profiles.

Topics: Aged; Angioplasty, Balloon, Coronary; Cross-Over Studies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Sirolimus; Treatment Outcome

To assess the safety and performance of the XIENCE V everolimus-eluting stent (EES) versus the TAXUS paclitaxel-eluting stent (PES) in the treatment of patients with de novo coronary artery lesions after a five-year follow-up period. Second-generation drug-eluting stents (DES) were developed with the aim of improving the safety profile of DES, after reports of stent thrombosis (ST) with first-generation devices. However, long-term follow-up data are scarce.. SPIRIT II was a multicentre, prospective, single-blind, clinical trial, randomising 300 patients with up to two de novo coronary artery lesions in a ratio of 3:1 to either a EES or a PES. The five-year clinical follow-up was completed in 244 patients (81%). At five-year follow-up, 19.5% of patients were on thienopyridine in the EES arm, while 30.5% were on the same therapy in the PES arm. Cardiac mortality was significantly lower in EES than in PES (1.5% vs. 7.3%, p=0.015). There was a trend towards lower cardiac death and MI (4.8% vs. 11.4%) and lower ID-TLR (4.7% vs. 9.4%) in EES than in PES. As a result, there was a consistent reduction in ID-MACE for EES vs. PES (ID-MACE 8.0% vs. 18.1%, p=0.018). In addition, the ARC-defined stent thrombosis rate was numerically lower in EES compared to PES (0.9% vs. 2.8%). No definite stent thrombosis events were observed after two years in the EES arm.. Five-year clinical follow-up of the SPIRIT II trial demonstrated the continuing long-term safety and efficacy of EES.

Topics: Aged; Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Single-Blind Method; Sirolimus; Treatment Outcome

To report the agreement between gray-scale intravascular ultrasound (GS-IVUS) and optical coherence tomography (OCT) in assessing the bioresorbable vascular scaffolds (BVS) structures and their respective reproducibility.. BVS are composed of an erodible polymer. Ultrasound and light signals backscattered from polymeric material differs from metallic stents using GS-IVUS and OCT.. Forty-five patients included in the ABSORB trial were treated with a 3.0 × 18 mm BVS and imaged with GS-IVUS 20 MHz and OCT post-implantation. Qualitative (ISA, side-branch struts, protrusion, and dissections) and quantitative (number of struts, lumen, and scaffold area) measurements were assessed by two investigators. The agreement and the inter- and intraobserver reproducibility were investigated using the kappa (κ) and the interclass correlation coefficient (ICC).. GS-IVUS and OCT agreement was predominantly poor at a lesion, frame, and strut level analysis (κ and ICC <0.4) for qualitative measurements. GS-IVUS demonstrated a reduced ability to detect cross-sections with ISA (4.5% vs. 20.6%), side-branch (SB) struts (6.3% vs. 7.8%), protrusions (3.2% vs. 9.6%), and dissections (0.2% vs. 9.0%) compared with OCT. GS-IVUS reproducibility was poor-moderate (κ and ICC <0.6) except for ISA and SB-struts (κ and ICC between 0.2 and 0.75). OCT showed an excellent reproducibility (κ and ICC > 0.75) except for the assessment of tissue protrusion (κ and ICC between 0.47 and 0.94). GS-IVUS reproducibility was poor-moderate (ICC ≤ 0.5) in assessing the number of struts but excellent with OCT (ICC > 0.85). The reproducibility to assess lumen and scaffold areas was excellent using both techniques (ICC > 0.85).. GS-IVUS has a poor capacity to detect qualitative findings post-BVS implantation and its reproducibility is low compared with OCT. The use of GS-IVUS should be limited when assessing lumen and scaffold areas.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Drug Carriers; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Observer Variation; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Late acquired incomplete stent apposition (ISA) is more common after drug-eluting stent (DES) than bare metal stent (BMS) implantation and has been associated with vascular hypersensitivity and stent thrombosis (ST). We investigated the impact of incidentally discovered ISA as assessed by intravascular ultrasound (IVUS) 8 months after DES implantation on the long-term clinical outcome.. A total of 194 patients with 221 lesions were prospectively followed through 5 years. At 8 months, IVUS showed evidence of ISA among 37 patients with 39 lesions (18%) (mean ISA(max) 4.7 ± 5.0 mm(2)), whereas no ISA was observed among 157 patients with 182 lesions. Incomplete stent apposition was more prevalent among segments treated with sirolimus-eluting (n = 103) than paclitaxel-eluting stents (n = 118) (27 vs. 9%, P = 0.001). Between IVUS investigation at the 8-month and 5-year follow-up, major adverse cardiac events occurred more frequently in patients with (18.9%, n = 7) than without ISA (7.0%, n = 11) (HR = 2.71, 95% CI: 1.05-6.96, P = 0.031). While there were no differences with respect to death, the rate of myocardial infarction was higher among patients with (13.5%, n = 5) than without ISA (1.9%, n = 3) (HR = 7.53, 95% CI: 1.79-31.6, P = 0.001). Very late ST was more common among patients with than without ISA [Academic Research Consortium-definite ST:13.5% (n = 5) vs. 0.6% (n = 1) HR = 23.2, 95% CI: 2.65-203, P < 0.001].. In the present study, the presence of ISA as assessed by IVUS 8 months after DES implantation was associated with a higher rate of myocardial infarction and very late stent thrombosis during long-term follow-up. The prognostic impact of ISA on long-term clinical outcomes requires further investigation.

Topics: Aged; Blood Vessel Prosthesis; Drug-Eluting Stents; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Incidental Findings; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Prospective Studies; Prosthesis Failure; Single-Blind Method; Sirolimus; Treatment Outcome; Tubulin Modulators; Ultrasonography, Interventional

To analyse the vasoreactivity of a coronary segment, previously scaffolded by the ABSORB bioresorbable vascular scaffold (BVS) device, in relationship to its intravascular ultrasound-virtual histology (IVUS-VH) composition and reduction in greyscale echogenicity of the struts. Coronary segments, transiently scaffolded by a polymeric device, may in the long-term recover a normal vasomotor tone. Recovery of a normal endothelial-dependent vasomotion may be enabled by scaffold bioresorption, composition of the underlying tissue, or a combination of both mechanisms.. All patients from the ABSORB Cohort A and B trials, who underwent a vasomotion test and IVUS-VH investigation at 12 and 24 months, were included. Acetylcholine (Ach) and nitroglycerin were used to test either the endothelial-dependent or -independent vasomotion of the treated segment. Changes in polymeric strut echogenicity-a surrogate for bioresorption-IVUS-VH composition of the tissue underneath the scaffold and their relationship with the pharmacologically induced vasomotion were all evaluated. Overall, 26 patients underwent the vasomotion test (18 at 12 and 8 at 24 months). Vasodilatory response to Ach was quantitatively associated with larger reductions over time in polymeric strut echogenicity (y= -0.159x- 6.85; r= -0.781, P< 0.001). Scaffolded segments with vasoconstriction to Ach had larger vessel areas (14.37 ± 2.50 vs. 11.85 ± 2.54 mm(2), P= 0.030), larger plaque burden (57.31 ± 5.96 vs. 49.09 ± 9.10%, P= 0.018), and larger necrotic core (NC) areas [1.39 (+1.14, +1.74) vs. 0.78 mm(2) (+0.20, +0.98), P= 0.006] compared with those with vasodilation.. Vasodilatory response to Ach, in coronary segments scaffolded by the ABSORB BVS device, is associated with a reduction in echogenicity of the scaffold over time, and a low amount of NC. In particular, the latter finding resembles the behaviour of a native coronary artery not caged by an intracoronary device.

Topics: Absorbable Implants; Acetylcholine; Aged; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Nitroglycerin; Plaque, Atherosclerotic; Sirolimus; Tissue Scaffolds; Vasodilation; Vasodilator Agents; Vasomotor System

Due to the limited distensibility of the everolimus-eluting bioresorbable vascular scaffold (ABSORB) compared to metallic platform stents, quantitative coronary arteriography (QCA) is a mandatory requirement for ABSORB deployment in the on-going ABSORB EXTEND Single-Arm Study. Visual assessment of vessel size in the ABSORB Cohort B study often lead to under and over-sizing of the 3 mm ABSORB in coronary vessels (recommended range of the vessel diameter ≥ 2.5 mm and ≤ 3.3 mm), with an increased risk of spontaneous incomplete scaffold apposition post ABSORB deployment. We report whether mandatory QCA assessment of vessel size pre-implantation, utilizing the maximal luminal diameter (Dmax) and established interpolated reference vessel diameter (RVD) measurements, has improved device/vessel sizing.. Pre-implantation post-hoc QCA analyses of all 101 patients from ABSORB Cohort B (102 lesions) and first consecutive 101 patients (108 lesions) from ABSORB EXTEND were undertaken by an independent core-laboratory; all patients had a 3 mm ABSORB implanted. Comparative analyses were performed.. Within ABSORB Cohort B, a greater number of over-sized vessels (> 3.3 mm) were identified utilizing the Dmax compared to the interpolated RVD (17 vessels, 16.7% vs. 3 vessels, 2.9%; P = 0.002). Comparative analyses demonstrated a greater number of appropriate vessel-size selection (75 vessels, 69.4% vs. 48 vessels, 47.1%; P = 0.001), a trend towards a reduction in implantation in small (< 2.5 mm) vessels (29 vessels, 26.9% vs. 40 vessels, 39.2%; P = 0.057) and a significant decrease in the implantation in large (> 3.3 mm) vessels (4 vessels, 3.7% vs. 17 vessels, 16.7%; P = 0.002) in ABSORB EXTEND. Bland-Altman plots suggested a good agreement between operator and core-laboratory calculated Dmax measurements.. The introduction of mandatory Dmax measurements of vessel size prior to ABSORB implantation significantly reduced the under-sizing of the 3.0 mm scaffold in large vessels validating the use of this technique in vessel sizing prior to ABSORB implantation.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Drug Carriers; Everolimus; Humans; Myocardial Ischemia; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tissue Scaffolds; Treatment Outcome; Ultrasonography, Interventional

The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).. To compare stents eluting biolimus from a biodegradable polymer with bare-metal stents in primary PCI.. A prospective, randomized, single-blinded, controlled trial of 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19, 2009, and January 25, 2011. Clinical follow-up was performed at 1 and 12 months.. Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582).. Primary end point was the rate of major adverse cardiac events, a composite of cardiac death, target vessel-related reinfarction, and ischemia-driven target-lesion revascularization at 1 year.. Major adverse cardiac events at 1 year occurred in 24 patients (4.3%) receiving biolimus-eluting stents with biodegradable polymer and 49 patients (8.7%) receiving bare-metal stents (hazard ratio [HR], 0.49; 95% CI, 0.30-0.80; P = .004). The difference was driven by a lower risk of target vessel-related reinfarction (3 [0.5%] vs 15 [2.7%]; HR, 0.20; 95% CI, 0.06-0.69; P = .01) and ischemia-driven target-lesion revascularization (9 [1.6%] vs 32 [5.7%]; HR, 0.28; 95% CI, 0.13-0.59; P < .001) in patients receiving biolimus-eluting stents compared with those receiving bare-metal stents. Rates of cardiac death were not significantly different (16 [2.9%] vs 20 [3.5%], P = .53). Definite stent thrombosis occurred in 5 patients (0.9%) treated with biolimus-eluting stents and 12 patients (2.1%; HR, 0.42; 95% CI, 0.15-1.19; P = .10) treated with bare-metal stents.. Compared with a bare-metal stent, the use of biolimus-eluting stents with a biodegradable polymer resulted in a lower rate of the composite of major adverse cardiac events at 1 year among patients with STEMI undergoing primary PCI.. clinicaltrials.gov Identifier: NCT00962416.

Topics: Absorbable Implants; Aged; Drug-Eluting Stents; Female; Humans; Male; Metals; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Revascularization; Polymers; Prospective Studies; Recurrence; Risk; Single-Blind Method; Sirolimus; Treatment Outcome

Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents.. The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post-device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years.. The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions.

Topics: Absorbable Implants; Adult; Aged; Aspirin; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Europe; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; New Zealand; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Research Design; Sample Size; Single-Blind Method; Sirolimus; Spectroscopy, Near-Infrared; Thiophenes; Tissue Scaffolds; Tomography, X-Ray Computed; Ultrasonography, Interventional

Percutaneous coronary intervention (PCI) is increasingly used to treat unprotected left main coronary artery stenosis, although coronary-artery bypass grafting (CABG) has been considered to be the treatment of choice.. We randomly assigned patients with unprotected left main coronary artery stenosis to undergo CABG (300 patients) or PCI with sirolimus-eluting stents (300 patients). Using a wide margin for noninferiority, we compared the groups with respect to the primary composite end point of major adverse cardiac or cerebrovascular events (death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization) at 1 year. Event rates at 2 years were also compared between the two groups.. The primary end point occurred in 26 patients assigned to PCI as compared with 20 patients assigned to CABG (cumulative event rate, 8.7% vs. 6.7%; absolute risk difference, 2.0 percentage points; 95% confidence interval [CI], -1.6 to 5.6; P=0.01 for noninferiority). By 2 years, the primary end point had occurred in 36 patients in the PCI group as compared with 24 in the CABG group (cumulative event rate, 12.2% vs. 8.1%; hazard ratio with PCI, 1.50; 95% CI, 0.90 to 2.52; P=0.12). The composite rate of death, myocardial infarction, or stroke at 2 years occurred in 13 and 14 patients in the two groups, respectively (cumulative event rate, 4.4% and 4.7%, respectively; hazard ratio, 0.92; 95% CI, 0.43 to 1.96; P=0.83). Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group as compared with 12 patients in the CABG group (cumulative event rate, 9.0% vs. 4.2%; hazard ratio, 2.18; 95% CI, 1.10 to 4.32; P=0.02).. In this randomized trial involving patients with unprotected left main coronary artery stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive. (Funded by the Cardiovascular Research Foundation, Seoul, Korea, and others; PRECOMBAT ClinicalTrials.gov number, NCT00422968.).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Coronary Artery Bypass; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Sirolimus

The aim of this study was to investigate the impact of patient and lesion complexity on outcomes with newer-generation zotarolimus-eluting stents (ZES) and everolimus-eluting stents (EES).. Clinical and angiographic outcomes of newer-generation stents have not been described among complex patients.. Patients enrolled in the RESOLUTE All Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) were stratified into "complex" and "simple.". Of 2,292 patients, 1,520 (66.3%) were complex and treated with ZES (n = 764) or EES (n = 756). Event rates were higher among complex patients, and results did not differ between ZES and EES, regardless of complexity. At 1 year, target lesion failure was 8.9% in ZES- and 9.7% in EES-treated complex patients (p = 0.66) and 6.8% in ZES- and 5.7% in EES-treated simple patients (p = 0.55). Rates of cardiac death (1.3% vs. 2.2%, p = 0.24), target-vessel myocardial infarction (4.3% vs. 4.4%, p = 0.90), and clinically indicated target lesion revascularization (4.4% vs. 4.0%, p = 0.80) were similar for both stent types among complex patients. Definite or probable stent thrombosis occurred in 20 (1.3%) complex patients with no difference between ZES (1.7%) and EES (0.9%, p = 0.26). Angiographic follow-up showed similar results for ZES and EES in terms of in-stent percentage diameter stenosis (22.2 ± 15.4% vs. 21.4 ± 15.8%, p = 0.67) and in-segment binary restenosis (6.6% vs. 8.0%, p = 0.82) in the complex group.. In this all-comers randomized trial, major adverse cardiovascular events were more frequent among complex than simple patients. The newer-generation ZES and EES proved to be safe and effective, regardless of complexity, with similar clinical and angiographic outcomes for both stent types through 1 year. (RESOLUTE-III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention; NCT00617084).

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; 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

The placement of sirolimus-eluting stents decreases the frequency of repeat revascularization procedures in patients undergoing percutaneous coronary intervention (PCI) in randomized clinical trials. However, there is uncertainty about the effectiveness of sirolimus-eluting stents, and increasing concern about their safety in routine clinical practice. From the prof. Samko PCI laboratory in Moscow, Russia, we identified 426 patients, who received either bare-metal stents alone or sirolimus-eluting stents alone during an index PCI procedure between March 1, 2002, and September 31, 2004.The primary outcomes of the study were the rates of target-lesion revascularization, myocardial infarction, death, late stent thrombosis. The 3-year rate of target-lesion revascularization was significantly lower among patients who received sirolimus-eluting stents than among those who received bare-metal stents (3.1% vs. 19 %, p=0.001). The 3-year mortality rate was not different between the bare-metal stent group and the sirolimus eluting stent group (5.9% vs. 7.2%, p=0.68), the 3-year rate of all ARC late stent thrombosis was similar in the two groups (5.9% and 7.2%, respectively; p=0.95). Sirolimus-eluting stents are effective in reducing the need for target-vessel revascularization without significantly increased rates of death, late stent thrombosis, myocardial infarction.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Drug-Eluting Stents; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Postoperative Care; Prospective Studies; Retrospective Studies; Risk Assessment; Sirolimus; Survival Rate; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Drug-Eluting Stents; Follow-Up Studies; Humans; Myocardial Infarction; Myocardial Ischemia; Paclitaxel; Sirolimus; Treatment Outcome

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

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

This article reports the 2-year clinical, angiographic, and intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial.. This was a prospective, single-blind clinical trial in which a total of 300 patients with de novo native coronary artery lesions were randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned at 2 years in all patients. A subset of 152 patients underwent serial angiographic and intravascular ultrasound analyses at 6 months and 2 years. After 2 years, target lesion failure (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES and PES, respectively (P=0.31). At 6 months, a significant reduction in angiographic in-stent late loss and percentage volume obstruction measured by intravascular ultrasound was observed in the EES group. However, at 2-year follow-up, a late increased intimal hyperplasia growth after implantation of an EES was observed. There were no significant differences between EES and PES for in-stent late loss (EES, 0.33+/-0.37 mm versus PES, 0.34+/-0.34 mm; P=0.84) and percentage volume obstruction (EES, 5.18+/-6.22% versus PES, 5.80+/-6.31%; P=0.65) at 2 years. The incidence of stent thrombosis was low and comparable in both groups (EES, 0.9%; PES, 1.4%).. Although the previously reported angiographic and clinical superiority of the EES has vanished over time, this report confirms and extends the previously demonstrated noninferiority in terms of in-stent late loss of the EES when compared with the PES up to 2-year follow-up. There were no significant differences between EES and PES in clinical, angiographic and intravascular ultrasound outcomes at 2 years.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; India; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; New Zealand; Paclitaxel; Prospective Studies; Single-Blind Method; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional

In this study, we examined whether cyclosporine was effective when combined with everolimus in clinical heart transplantation (HT).. From August 2004 to July 2007, 108 adult patients underwent primary HT. The main exclusion criteria were: donors > 60 years; cold ischemia times > 6 hours; recipients of multiorgan transplantation or a previous transplantation; and panel-reactive antibodies > or = 25%. The cyclosporine plus everolimus regimen (group CE, n = 32) was suggested first; upon refusal or if the recipient or donor was positive for hepatitis B surface antigen or PCR + hepatitis C infection, then patient was randomly assigned to success cyclosporine plus mycophenolate mofetil (MMF; group CM, n = 24) or tacrolimus plus MMF (group TM, n = 25). All patients underwent similar operative procedures and postoperative care with protocol endomyocardial biopsies.. No 30-day mortality was noted in any group. The efficacy failure rates were 3%, 25%, and 16% in groups CE, CM, and TM, respectively (P = .04 between groups CE and CM). The 1-year survivals were 96.7% +/- 18.1%, 89.7% +/- 29.8%, and 81.0% +/- 35.5% for groups CE, CM, and TM, respectively (P = .04 between groups CE and TM). The 3-year survival rates were 91.9% +/- 28.3%, 79.8% +/- 46.0%, and 81.0% +/- 35.5% in groups CE, CM, and TM, respectively.. The 3 immunosuppressive regimens offered good efficacy after HT. The cyclosporine plus everolimus regimen showed a significantly better result with less efficacy failure (compared with cyclosporine plus MMF: 3% vs 25%) and better 1-year survival compared with tacrolimus plus MMF: 96.7% vs 81.0%.

Topics: Adult; Cardiomyopathy, Dilated; Cyclosporine; Drug Therapy, Combination; Everolimus; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Myocardial Ischemia; Patient Selection; Sirolimus; Survival Analysis; Survivors; Tacrolimus; Tissue Donors; Treatment Outcome

To assess the safety and efficacy of the XTENT customisable drug-eluting stent system in the treatment of patients with single long or multiple coronary lesions referred for PCI.. The CUSTOM-II trial enrolled 100 patients with de novo lesions in native coronary arteries presenting with either single long lesions (n=69) of > or =20 mm length or up to two lesions with a total cumulative anticipated stent length of 60 mm of stent (n=31). Patients were assessed angiographically at six months, and clinically at one year. Of the 100 patients enrolled, nine patients experienced a MACE, including five patients whose MACE occurred during index hospitalisation (two non-Q-MI, two Q-MI and one probable stent thrombosis-related death), and four target lesion revascularisations (TLR) at six months. No MACE or stent thrombosis was reported between six and 12 months follow-up. In-segment late loss at 6-months was 0.22 +/- 0.28 mm, and in-stent late loss had a range of 0.31 +/- 0.31 mm.. The XTENT customisable stent is clinically safe and efficacious as judged by angiographic and clinical variables through 12 months follow-up. Further follow-up and larger randomised comparative studies are needed for its clinical positioning.

Topics: Aged; Angioplasty, Balloon, Coronary; Coated Materials, Biocompatible; Coronary Angiography; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Risk Factors; Sirolimus; Treatment Outcome

Despite the effectiveness of sirolimus- and paclitaxel-eluting stents in reducing intimal hyperplasia (IH) and the need for repeat revascularization, concerns about their long-term safety have motivated the search for new drug-eluting stents (DES). Recently developed, the ZoMaxx stent combines a sirolimus-analogous agent (zotarolimus), featuring a phosphorycoline polymer and stainless steel and tantalum platform. We sought to assess the efficacy of this new DES in reducing IH.. A total of 40 patients were treated with the ZoMaxx stent and compared to 50 patients treated with its non-drug-eluting equivalent, the TriMaxx stent. Only single de novo lesions in native coronary vessels greater than or equal to 3.0 mm were enrolled. Serial quantitative coronary angiography and intravascular ultrasound (IVUS) images were obtained at baseline and 6- month follow up. All patients were clinically followed for 1 year. This analysis aimed to compare the percent of IH between the 2 stents. Secondarily, we assessed in-segment late loss, binary restenosis and major adverse cardiac events.. Baseline patient and lesion characteristics were comparable between the 2 groups. At follow up, zotarolimus efficiently suppressed neointimal hyperplasia formation with a marked reduction in the percentage of stent obstruction by IVUS (4.6 +/- 3.6% vs. 31.2 +/- 16%; p < 0.0001). Almost 90% of the segments stented with ZoMaxx did not exhibit more than 10% of obstruction. After 1 year, 12 patients treated with the TriMaxx and 2 patients treated with the ZoMaxx presented in-segment binary restenosis (p = 0.03).. In this initial experience, ZoMaxx proved to be clinically safe and superior to its non-drug-coated equivalent in reducing in-stent IH formation and restenosis.

Topics: Coated Materials, Biocompatible; Coronary Angiography; Female; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Pilot Projects; Prospective Studies; Prosthesis Implantation; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Analysis of the 3-year outcome of the original population of the TAXi trial which compared the efficacy of the paclitaxel (PES) and the sirolimus (SES) stents in a randomized "real world" investigation.. The widespread use of drug-eluting stents strongly modified the world of interventional cardiology. The TAXi trial was a randomized comparison between PES and SES and showed similar efficacy between the two prostheses. Recently, emerging discussions raised questions about potential long-term risk with the use of DES. The present work attempts to describe the long-term outcome of the patients compared during the TAXi trial.. During April 2003 and January 2004, 202 patients were prospectively randomly assigned to the PES group (102 patients) and to the SES group (100 patients). The primary aim of the present investigation was the comparison of combined incidence of cardiac death, myocardial infarction, and target lesion revascularization within 36-months.. No difference in mortality of all causes was noted in the PES and the SES groups (3% vs. 7%, P=0.98) or in major adverse cardiac event free survival (89% vs. 83%, P=0.28). Four stent thromboses were observed, two in the PES group (205 and 788 days) and two in the SES group (210 and 772 days).. The long-term outcome analysis of the TAXi trial confirms available published data showing the equivalence of PES and SES on clinical basis.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Paclitaxel; Prospective Studies; Prosthesis Design; Research Design; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome

Sirolimus-eluting stents markedly reduce the risk of restenosis compared with bare metal stents. However, it is not known whether there are differences in effectiveness between bare metal and sirolimus-eluting stents in patients with total coronary occlusions.. In a prospective, randomized, single-blind, 2-center trial, we enrolled 200 patients with total coronary occlusions: Half (n = 100) were randomly assigned to receive bare metal BxVelocity stents and half (n = 100) to receive sirolimus-eluting Cypher stents. The primary end point was angiographic binary in-segment restenosis rate at 6-month follow-up. Secondary end points were a composite of major adverse cardiac events, target vessel failure, binary in-stent restenosis rate, in-stent and in-segment minimal lumen diameter, percent diameter stenosis, and late luminal loss at 6-month follow-up. The sirolimus stent group showed a significantly lower in-stent binary restenosis rate of 7% compared with 36% in the bare metal stent group (P < 0.001). The in-segment binary restenosis rate was 11% in the group receiving a sirolimus stent versus 41% in the bare metal stent group (P < 0.0001), resulting in a target lesion revascularization rate of 4% in the sirolimus group versus 19% in the bare metal group (P < 0.001). Patients who received the drug-eluting stent also had significantly lower rates of target vessel revascularization, target vessel failure, and all major adverse cardiac events.. In patients with total coronary occlusions, use of the sirolimus-eluting stents are superior to the bare metal stents with significant reduction in angiographic binary restenosis, resulting in significantly less need for target lesion and target vessel revascularization.

Topics: Aged; Anti-Bacterial Agents; Coronary Angiography; Coronary Stenosis; Equipment Design; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Risk Factors; Single-Blind Method; Sirolimus; Stents

Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4'-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.

Topics: Aging; Angelica; Animals; Autophagy; Caenorhabditis elegans; Cation Transport Proteins; Cell Death; Cell Line; Drosophila melanogaster; Flavonoids; GATA Transcription Factors; Gene Expression Regulation; Humans; Longevity; Male; Mechanistic Target of Rapamycin Complex 1; Medicine, East Asian Traditional; Mice; Mice, Inbred C57BL; Myocardial Ischemia; Plant Extracts; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Sirolimus; Transcription Factors

Patients with diabetes mellitus (DM) have poorer outcomes after percutaneous coronary intervention than patients without diabetes. The Abluminus DES+™ drug-eluting stent (DES) features a novel technology of fusion coating of PLLA bioresorbable polymer on both the abluminal surface of the stent and exposed parts of the balloon. The aim of this study was to evaluate the efficacy/safety profile of the Abluminus DES+ in an all-comers population with minimal exclusion criteria and with a specific focus on diabetic patients.. Multicenter, prospective, all-comers registry performed in 31 centers in India. Patients were analyzed according to the diagnosis of DM and insulin dependency (ID or Non ID): non-DM (1256 patients), NIDDM (498 patients), IDDM (99 patients). The primary endpoint was a composite of device-oriented major adverse cardiac events (MACE): cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target lesion revascularization (TLR)/ target vessel revascularization (TVR) at 1 year. Stent thrombosis (ST) at any time point was also recorded.. The MACE rate at 1 year in the overall population was 2.3% and it was mainly driven by a 1.57% rate of TLR/TVR. Although patients with IDDM showed slightly higher figures for MACE (non-DM 2.3%, NIDDM 2.8%, IDDM 4%, P=0.09), as well as for single end-points, none of them reached statistical significance. The rate of ST was 0.56%, 0.4%, 1% for non-DM, NIDDM and IDDM group, respectively (P=0.6).. The performance of the Abluminus DES+ is consistent among patients with or without diabetes, regardless the insulin dependency.

Topics: Absorbable Implants; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Humans; India; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Registries; Sirolimus; Treatment Outcome

Second-generation drug-eluting stents (DESs) have shown higher safety and efficacy compared with first-generation DESs. This effect was achieved by improving biocompatibility using an interalia cobalt-chromium construction, thinner stent struts and biodegradable polymers.. To assess clinical and angiographic outcomes of patients receiving a novel second-generation cobalt-chromium sirolimus-eluting stent.. A total of 424 consecutive patients who received an Alex stent were enrolled in the registry from January to December 2012. The primary outcome measure was the occurrence of 12-month major cardiac adverse events, defined as cases of death, nonfatal myocardial infarction and target lesion revascularization. Quantitative coronary angiography for 240 randomly selected patients was performed by an independent Corelab.. The primary endpoint occurred in 31 of 424 patients (7.3%). The rates of death, nonfatal myocardial infarction and target lesion revascularization were 3.3, 2.6 and 3.5%, respectively. According to the definition established by the Academic Research Foundation, definitive and probable stent thrombosis (ST) occurred in 1.6% (7/424) of patients, including six cases of early ST and one case of late ST. The acute device success rate was 98.5%.. The ALEX Registry provides evidence for the safety and effectiveness of the study device in a relevant population. Quantitative analysis showed a satisfactory performance of the study device for complex coronary lesions. The 12-month rates of major cardiac adverse event and ST were similar to those of other second-generation DES registries.

Topics: Absorbable Implants; Aged; Angina, Stable; Angina, Unstable; Antibiotics, Antineoplastic; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Polymers; Registries; Sirolimus; Treatment Outcome

To report the six-month angiographic and two-year clinical outcome data from the first-in-man study with the Ultimaster DES, a thin-strut cobalt-chromium sirolimus-eluting stent (SES) with an innovative abluminal-gradient-coated bioresorbable polymer.. CENTURY is a multicentre, single-arm, prospective study that enrolled 105 patients (113 lesions) with coronary artery disease. All patients were scheduled to have an angiographic follow-up at six months, while 45 and 20 patients respectively had IVUS and OCT assessments. The primary endpoint was six-month in-stent late lumen loss. Secondary endpoints included clinical, IVUS and OCT outcomes. Clinical follow-up is available up to two years and will continue up to five years. Procedural success was 97.1% and device success was 100%. Angiographic late loss at six months was 0.04±0.35 mm, also reflected in a low binary restenosis rate of 0.9% and confirmed by IVUS-assessed neointimal volume obstruction of 1.02±1.62%. The mean strut coverage assessed by OCT was 96.2% with 1.66±4.02 malapposed stent struts. There were no deaths in the study, three (2.9%) periprocedural and one (0.9%) spontaneous myocardial infarction, not related to the target vessel. At one and two years, the target lesion failure rate was 3.8% and 5.7%, while the TLR rate was 1.9% and 2.8%, respectively. There was one acute definite stent thrombosis.. The Ultimaster™ novel bioresorbable polymer sirolimus-eluting stent demonstrated good performance, including high procedural success and strong suppression of neointimal proliferation at six months. Good safety and effectiveness were shown up to two years in the studied population.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Neointima; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Topics: Absorbable Implants; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Myocardial Ischemia; Sirolimus; Tissue Scaffolds

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

Topics: Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Myocardial Ischemia; Percutaneous Coronary Intervention; Sirolimus

We aimed to investigate the feasibility, initial safety and efficacy of coronary intervention using FIREHAWK®, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES), in patients with complex anatomical and clinical scenarios.. A total of 57 patients (79 lesions) with complex anatomical and clinical scenarios implanted with the FIREHAWK® SES between March and November 2014 were studied. The primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac death, target vessel-myocardial infarction (TV-MI), and ischemia-driven target lesion revascularization (iTLR). Optical coherence tomography and intravascular ultrasound was performed according to the discretion of operators.. 28.1% of patients presented acute myocardial infarction and all patients had at least one of the following anatomical and locational complexity: multi-vessel disease (64.9%), left main disease (24.6%), chronic total occlusion (17.5%), bifurcation (56.1%), and heavily calcified lesions (10.5%). One patients experienced coronary perforation during the procedure and resolved without any additional treatment. Device success was 100%, clinical success was 100%. There was 1 (1.8%) TLF occurred at follow-up of 150 ± 65 days. One patients had non-iTLR. Out of 2 non-Q-wave MI, 1 patient experienced TV-MI, but no death and stent thrombosis were reported. OCT and IVUS imaging showed a high rate of covered struts and low neointimal hyperplasia at follow-up.. The study showed the feasibility, initial safety and efficacy of coronary intervention using FIREHAWK® SES for treating patients with complex anatomical and clinical scenarios. The performance of the FIREHAWK® SES in complex patients justifies the conduct of a large, randomized trial.

Topics: Aged; Coronary Artery Disease; Drug-Eluting Stents; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Polymers; Prosthesis Design; Sirolimus; Tomography, Optical Coherence

Topics: Absorbable Implants; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Myocardial Ischemia; Sirolimus; Tissue Scaffolds

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

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

Women have a worse outcome than men after percutaneous coronary intervention (PCI). However, in the drug-eluting stent (DES) era, limited data are available about the impact of gender-related differences on clinical outcome. Furthermore, many series have also included patients previously treated by coronary-artery bypass grafts or PCI, which may bias the evaluation of DES-related clinical events at follow up. We aimed to assess the impact of gender on clinical outcomes in a consecutive series of patients at first manifestation of coronary artery disease (CAD) undergoing PCI with mTOR-inhibitor DES.. A total of 138 consecutive patients (age 64 ± 13 years, female gender 29%) undergoing successful mTOR-inhibitor DES implantation [sirolimus-eluting stent (SES); zotarolimus-eluting stent (ZES); and everolimus-eluting stent (EES)] for the treatment of stable chronic angina or an acute coronary syndrome, as their first clinical manifestation of CAD, were prospectively enrolled between February 2008 and May 2009. Major adverse cardiac events (MACE), defined as a combination of cardiac death, myocardial infarction (MI), and clinically driven target lesion revascularization (TVR) at 12-month follow up, constituted the endpoint of the study. Fifty-one (37%) patients received SES; 46 (33%) patients received ZES; and 41 (30%) patients received EES. At follow up, 21 (15%) patients experienced a MACE. Three (2%) patients had cardiac death, five (4%) had MI, while 13 (9%) patients underwent clinically driven TVR. MACE occurred more frequently in females than males [10 (25%) vs. 11 (11%), p = 0.05]. At Cox regression analysis, the only independent predictors of MACE were female gender and implantation of more than one stent [hazard ratio (HR) 3.70, 95% confidence interval (CI) 1.46-9.36, p = 0.006; HR 1.26, 95% CI 0.99-2.74, p = 0.01, respectively].. In conclusion, our finding suggests that women may have a worse outcome as compared with men after mTOR-inhibitor DES implantation.

Topics: Aged; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Italy; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Prospective Studies; Risk Assessment; Sex Factors; Sirolimus; Survival Rate; 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 aim was to ascertain the 1-year clinical outcomes of 1,234 patients who underwent implantations of sirolimus-eluting stents (SES) for acute myocardial infarction (MI) in the multinational e-SELECT registry.. Fifteen thousand and one hundred and forty-seven patients treated with SES were entered in the e-SELECT registry, of whom 1,234 presented within <24 hours of onset of acute MI.. At 1 year, the rates of major adverse cardiac events (MACE) (5.5% vs. 4.8%; P = 0.28) were similarly low in the acute and no acute MI groups. The rates of definite/probable stent thrombosis (ST) were higher in the acute MI group (2.1%vs; 0.88%, P < 0.001). ST was a strong independent predictor of death at 1 year (HR 13.4; 95% CI 5.0, 36.0; P < 0.001) and MI (HR 58.9; 95% CI 26.9, 129.1; P < 0.001). Dual antiplatelet therapy (DAPT) compliance at 6 months was 96.0% in the acute MI versus 94.5% in the no acute MI group (P = 0.03).. In selected patients presenting within <24 hours of acute MI onset and highly compliant with DAPT, SES implantation was associated with similar rates of MACE, though higher rates of ST, as compared to no acute MI patients.

Topics: Drug-Eluting Stents; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Registries; Sirolimus; Treatment Outcome

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Everolimus; Humans; Myocardial Ischemia; Sirolimus; Tissue Scaffolds

Topics: Coronary Vessels; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Myocardial Ischemia; Plaque, Atherosclerotic; Sirolimus; Vasodilation

Recent studies have reported the development of neoatherosclerosis inside stents and subsequent acute coronary syndrome secondary to disruption of neointimal hyperplasia. The aim of the study was to compare the characteristics of neointimal hyperplasia and its time course between bare metal stents (BMSs) and drug-eluting stents (DESs) using optical coherence tomography. A total of 138 stents were divided into 3 groups according to the follow-up period: early phase, <9 months (25 BMSs and 27 DESs); intermediate phase, ≥9 and <48 months (18 BMSs and 43 DESs); and delayed phase, ≥48 months (13 BMSs and 12 DESs). Optical coherence tomographic analysis included the presence of lipid-laden intima, percentage of lipid-rich plaque, and signal attenuation. The optical coherence tomographic findings were compared between the BMSs and DESs in each period, and the difference between the periods was also determined. In the early phase, a greater incidence of lipid-laden plaque (37% vs 8%, p = 0.02) and a greater percentage of lipid-rich plaque (12.9 ± 25.1% vs 1.2 ± 4.3%, p = 0.01) were found in the DESs than in the BMSs. In the intermediate phase, the DES group continuously showed a significantly greater incidence of lipid-laden plaque (63% vs 28%, p = 0.03) and greater percentage of lipid-rich plaque (24.8 ± 28.1% vs 4.1 ± 7.3%, p <0.01). In addition, signal attenuation was greater in the DES group, suggesting early changes in neointimal hyperplasia properties. In the delayed phase, lipid-laden plaque was the predominant type in both groups. In conclusion, lipid-rich neoatherosclerosis develops inside stents earlier in DESs than in BMSs. After 48 months, most restenotic stents will have developed lipid-laden neointima in both groups.

Topics: Acute Coronary Syndrome; Atherosclerosis; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Incidence; Male; Massachusetts; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

Malignancy is not uncommon with immunosuppressive therapy, but pancreatic cancer is infrequently complicated in recipients of heart transplantation. Here we report a transplant case diagnosed with pancreatic cancer 4 years and 8 months after the heart transplantation. We changed the immunosuppressive regimen after the malignancy was detected, and administered everolimus along with chemotherapy using S-1, an oral fluoropyrimidine prodrug. The patient lived for 8 months after the diagnosis, and received metallic stenting for the biliary and duodenal obstruction. Also, to the best of our knowledge, this is the first report about chemotherapy and endoscopic intervention for pancreatic cancer in a heart transplantation patient.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Cholestasis, Extrahepatic; Combined Modality Therapy; Drug Combinations; Drug Therapy, Combination; Duodenal Obstruction; Everolimus; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Postoperative Complications; Sirolimus; Stents; Tegafur

To examine serial change in the residual plaque behind the sirolimus-eluting stent (SES) using coronary angioscopy in patients with SES implantation and to identify its baseline determinants.. Previous coronary angioscopic studies have demonstrated that SES enhances the yellow grade of residual plaque during follow-up period.. A total of 42 patients with stable angina pectoris or silent ischemic heart disease, who had a successful SES implantation were examined by coronary angioscopy both at the baseline (SES implantation) and the follow-up period (9-14 month follow-up). The patients were divided into three groups as: worsened group (WS: yellow color grade of coronary plaque at the follow-up period was worsened compared to the baseline period, n=15), no change group (NP: no change compared to the baseline, n=16), and improved group (IP: improved compared to the baseline, n=11). Then, the determinants of the nominal change of yellow color grade were examined by multiple regression analysis.. The low-density lipoprotein cholesterol (LDL-C) level in IP group at the follow-up was significantly decreased compared to baseline (from 120.0±29.8mg/dl to 74.3±16.7mg/dl, p=0.0005), and was the lowest among three groups (WS: 103.5±16.4mg/dl, NC: 105.7±18.7mg/dl, and IP: 74.3±16.7mg/dl). Multiple regression analysis revealed that family history, statin administration, baseline serum creatinine, baseline 'in-stent' thrombus, and follow-up LDL-C were significant determinants to the nominal change of yellow color grade after the SES implantation (p<0.0001).. Serial change in tissue characteristics within residual plaque under SES is determined by several factors, especially LDL-C level as well as statin administration. Adequate management of LDL-C by statins might be crucial for stabilizing residual plaque after SES implantation.

Topics: Aged; Angina, Stable; Angioscopy; Cholesterol, LDL; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Myocardial Ischemia; Plaque, Atherosclerotic; Regression Analysis; Sirolimus

The first generation of the everolimus-eluting bioresorbable vascular scaffold (BVS 1.0) showed an angiographic late loss higher than the metallic everolimus-eluting stent Xience V due to scaffold shrinkage. The new generation (BVS 1.1) presents a different design and manufacturing process than the BVS 1.0. This study sought to evaluate the differences in late shrinkage, neointimal response, and bioresorption process between these two scaffold generations using optical coherence tomography (OCT).. A total of 12 lesions treated with the BVS 1.0 and 12 selected lesions treated with the revised BVS 1.1 were imaged at baseline and 6-month follow-up with OCT. Late shrinkage and neointimal area (NIA) were derived from OCT area measurements. Neointimal thickness was measured in each strut. Strut appearance has been classified as previously described. Baseline clinical, angiographic, and OCT characteristics were mainly similar in the two groups. At 6 months, absolute and relative shrinkages were significantly larger for the BVS 1.0 than for the BVS 1.1 (0.98 vs. 0.07 mm² and 13.0 vs. 1.0%, respectively; P = 0.01). Neointimal area was significantly higher in the BVS 1.0 than in the BVS 1.1 (in-scaffold area obstruction of 23.6 vs. 12.3%; P < 0.01). Neointimal thickness was also larger in the BVS 1.0 than in the BVS 1.1 (166.0 vs. 76.4 µm; P < 0.01). Consequently, OCT, intravascular ultrasound, and angiographic luminal losses were higher with the BVS 1.0 than with the BVS 1.1. At 6 months, strut appearance was preserved in only 2.9% of the BVS 1.0 struts, but remained unchanged with the BVS 1.1 indicating different state of strut microstucture and/or their reflectivity.. The BVS 1.1 has less late shrinkage and less neointimal growth at 6-month follow-up compared with the BVS 1.0. A difference in polymer degradation leading to changes in microstructure and reflectivity is the most plausible explanation for this finding.

Topics: Aged; Biocompatible Materials; Blood Vessel Prosthesis; Coronary Angiography; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Prosthesis Design; Prosthesis Failure; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence; Ultrasonography, Interventional

It has been reported that the overlap of sirolimus-eluting stents (SESs) is associated with greater in-stent late lumen loss and more angiographic restenosis. The purpose of this study was to evaluate whether the site of such overlap shows increased or decreased late lumen loss as assessed by quantitative coronary angiogram.. We compared 7-month angiographic late lumen loss at the site of overlap in patients with multiple overlapping stents (overlap SES group, n=48) to that in patients with single stents (single SES group, n=144). With regard to baseline angiographic characteristics and procedural results, there were significant differences between the overlap SES group and the single SES group in lesion complexity, lesion length and reference diameter, minimal lumen diameter, and mean stent length. In-stent late lumen loss at the 7-month follow-up did not differ significantly between the two groups (overlap SES 0.25 ± 0.61 mm vs. single SES 0.10 ± 0.55 mm, p=0.11). Furthermore, the site of overlap in the overlap SES group did not show greater late lumen loss compared to the stented area in the single SES group (0.17 ± 0.55 mm vs. 0.10 ± 0.55 mm, p=0.43). The overlap SES group tended to be associated with an increase in binary restenosis compared with the single SES group (22.8% vs. 12.8%, p=0.08), while this value was 4.2% at the site of overlap. There were no significant differences in death, myocardial infarction, target lesion revascularization, or stent thrombosis between the two groups. In addition, stent length was the most independent factor of late lumen loss in the overlap SES group by multivariate logistic analysis, whereas it was not an independent factor of late lumen loss of the SES overlap segment.. The site of overlap of overlapping SES dose not associate with greater late lumen loss or a higher in-stent binary restenosis rate compared to single SES implantation. The overlapping of SES by itself did not increase in-stent late lumen loss.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Sirolimus; Time Factors

To examine the long-term outcome of the stent fracture (SF) and the potential predictive factors contributing to in-stent restenosis (ISR) in the fractured stent.. The SF is thought to be a higher risk of ISR in drug-eluting stent, although SF does not always develop ISR.. The consecutive 1,228 de novo lesions in 1,079 patients who underwent sirolimus-eluting stents implantation and assessed by 8 months follow-up coronary angiography were retrospectively analyzed.. One hundred and seventeen SFs (9.5%) were identified in 100 patients and 22 (18.8%) SFs revealed ISR at the first follow-up. In addition, 16 (13.7%) developed new ISRs from 95 residual SFs without ISR prior to the second follow-up. Overall, 38 (32.5%) of all 117 SFs developed ISR, and 16 (42.1%) of 38 SFs occurred in a late phase beyond the first 8 months follow-up. A higher risk of ISR in the SF site was associated with the chronic total occlusion (ISR vs. no ISR: 34.2% vs. 16.5%, P = 0.0304), calcified lesions (55.3% vs. 34.2%, P = 0.0299), and correspondence 89.5% versus 43.0%, P < 0.0001 (SF site occurring at the original target lesion site) in the univariate analysis. The correspondence was identified as the only strong predictive factor for ISR at the SF site according to a multivariate logistic regression analysis (odds ratio 12.6, 95% confidence interval 3.82-53.5, P < 0.0001).. SF occurring at the site of the original target lesion was a strong independent predictor of ISR. This indicates the need for a careful, long-term follow-up in those situations, even when no significant ISR is initially detected.

Topics: Adult; Aged; Aged, 80 and over; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Prosthesis Failure; Retrospective Studies; Sirolimus; Treatment Outcome

The purpose of the present study was to evaluate the 3-year clinical outcomes after percutaneous coronary intervention with sirolimus-eluting stents in patients with insulin-treated diabetes mellitus (DM-insulin) and those with non-insulin-treated DM (DM-non-insulin) compared to patients without DM. Of 10,778 consecutive patients treated exclusively with sirolimus-eluting stents in the j-Cypher registry, we identified 996 patients with DM-insulin, 3,404 with DM-non-insulin, and 6,378 without DM. Compared to the non-DM group, the adjusted risk of a serious cardiovascular event (composite of all-cause death, myocardial infarction, and stroke) was significantly greater in the DM-insulin group (hazard ratio 1.12, 95% confidence interval [CI] 1.03 to 1.23; p = 0.01), but not in the DM-non-insulin group (hazard ratio 1.02, 95% CI 0.96 to 1.09; p = 0.47). The adjusted risk of target lesion revascularization was significantly greater in both the DM-insulin group (odds ratio 1.52, 95% CI 1.19 to 1.92; p = 0.0006) and the DM-non-insulin group (odds ratio 1.24, 95% CI 1.05 to 1.45; p = 0.009). In conclusion, a diabetes-associated excess risk of target lesion revascularization was found, regardless of insulin use in this large, real-world study of Japanese patients with sirolimus-eluting stent implantation. However, regarding serious cardiovascular events, an excess risk was seen only in the DM-insulin group. The risk of serious cardiovascular events was similar between the DM-non-insulin and non-DM groups.

Topics: Aged; Angioplasty, Balloon, Coronary; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Male; Myocardial Ischemia; Prospective Studies; Registries; Sirolimus; Treatment Outcome

Aim of the study was to assess participation in development of restenosis of circulating in blood progenitor cells of stromal line of differentiation and polymorphonuclear granulocytes. We compared levels of osteonectin positive progenitor cells, neutrophils, eosinophils, and basophils in blood of patients with ischemic heart disease (IHD) in whom according to data of angiographic study after endovascular myocardial revascularization with the help of stents with drug coating (Cypher, Cordis Corp, USA) restenosis was detected (n=15), in patients without restenosis (n=23), and in healthy persons (n=17). Levels of stromal progenitor cells and polymorphonuclear granulocytes in blood were measured with the help of methods of flow cytometry. In groups of patients with IHD with and without restenosis number of osteonectin positive cells in blood was higher than in healthy subjects (2.4+/-0.7 and 2.5+/-0.9 vs 1.5+/-0.5 cells/ microL, respectively, p=0.004) without significant differences between groups (p=0.59). These 2 groups of patients did not differ by numbers of leukocytes, neutrophils, and basophils in blood. At the same time we found that in patients with restenosis number of eosinophils in blood was significantly greater than in the group of patients without restenosis (262+/-68 vs 124+/-67 cells/ microL, respectively p<0.001). Moreover in patients with level of eosinophils exceeding 170 cells/ microL rate of development of restenosis was 74% against 5% in patients with number of eosinophils less than 170 cells/ microL (p<0.001). Thus level of stromal progenitor cells in blood of patients with IHD was higher than in healthy persons and remained equally high in groups with and without restenosis. Number of blood eosinophilic leukocytes in patients who had been subjected to coronary stenting in whom later restenosis developed was significantly higher than in patients without restenosis. The data obtained indicate at the presence of link between development of in - stent restenosis and elevated content of eosinophilic granulocytes in blood of patients with IHD.

Topics: Adult; Blood Cell Count; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Flow Cytometry; Follow-Up Studies; Humans; Immunosuppressive Agents; Leukocytes; Male; Myocardial Ischemia; Myocardial Revascularization; Osteonectin; Prognosis; Prosthesis Design; Sirolimus; Stem Cells; Stromal Cells; Treatment Outcome; Young Adult

Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings.. Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 μm versus 123.0±102.5 μm; P<0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P=0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P=1.0), the cross sections with ESL increased (9.6% versus 15.2%; P=0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm(2) versus 0.62±0.68 mm(2) and 16.6±5.4° versus 65.1±38.4°; P<0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P=1.0). All thrombi were identified in patients who had cross sections with ESL.. The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.

Topics: Aged; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Neointima; Prevalence; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence

A bimodal distribution of measures of restenosis has been demonstrated at 6-8 months after bare metal stent implantation. Drug-eluting stent (DES) treatment has attenuated the impact of certain factors (eg, diabetes) on restenosis but its effect on the distribution of indices of restenosis is not known.. To perform a detailed analysis of the metrics of restenosis indices after DES implantation. Design, settings,. Prospective observational study of patients undergoing DES implantation (Cypher, sirolimus-eluting stent; or Taxus, paclitaxel-eluting stent) at two German centres, with repeat angiography scheduled at 6-8 months after coronary stenting.. In-stent late luminal loss (LLL) and in-segment percentage diameter stenosis (%DS) as determined by quantitative coronary angiography at recatheterisation.. Paired cineangiograms were available for 2057 patients. Overall mean (SD) LLL was 0.31 (0.50) mm; mean (SD) %DS was 30.3 (15.7)%. Distribution of both LLL and %DS differed significantly from normal (Kolmogorov-Smirnov test; p<0.001 for each). For both parameters a mixed distribution model better described the data (likelihood ratio test with 3df; p<0.001 for each). This consisted of two normally distributed subpopulations with means (SD) of 0.10 (0.25) mm and 0.69 (0.60) mm for LLL, and means (SD) of 22.2 (8.6)% and 40.1 (16.6)% for %DS. The results were consistent across subgroups of DES type, "on-label" versus "off-label" indication, and presence or absence of diabetes.. LLL and %DS at follow-up angiography after DES implantation have a complex mixed distribution that may be accurately represented by a bimodal distribution model. The introduction of DES treatment has not resulted in elimination of a variable propensity to restenosis among subpopulations of patients with stented lesions.

Topics: Aged; Blood Vessel Prosthesis; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Myocardial Ischemia; Paclitaxel; Prospective Studies; Prosthesis Failure; Sirolimus; Treatment Outcome; Tubulin Modulators

Long-term outcomes after stenting of an unprotected left main coronary artery (ULMCA) with drug-eluting stents have not been addressed adequately despite the growing popularity of this procedure.. j-Cypher is a multicenter prospective registry of consecutive patients undergoing sirolimus-eluting stent implantation in Japan. Among 12 824 patients enrolled in the j-Cypher registry, the unadjusted mortality rate at 3 years was significantly higher in patients with ULMCA stenting (n=582) than in patients without ULMCA stenting (n=12 242; 14.6% versus 9.2%, respectively; P<0.0001); however, there was no significant difference between the 2 groups in the adjusted risk of death (hazard ratio 1.23, 95% confidence interval 0.95 to 1.60, P=0.12). Among 476 patients whose ULMCA lesions were treated exclusively with a sirolimus-eluting stent, patients with ostial/shaft lesions (n=96) compared with those with bifurcation lesions (n=380) had a significantly lower rate of target-lesion revascularization for the ULMCA lesions (3.6% versus 17.1%, P=0.005), with similar cardiac death rates at 3 years (9.8% versus 7.6%, P=0.41). Among patients with bifurcation lesions, patients with stenting of both the main and side branches (n=119) had significantly higher rates of cardiac death (12.2% versus 5.5%; P=0.02) and target-lesion revascularization (30.9% versus 11.1%; P<0.0001) than those with main-branch stenting alone (n=261).. The higher unadjusted mortality rate of patients undergoing ULMCA stenting with a sirolimus-eluting stent did not appear to be related to ULMCA treatment itself but rather to the patients' high-risk profile. Although long-term outcomes in patients with ostial/shaft ULMCA lesions were favorable, outcomes in patients with bifurcation lesions treated with stenting of both the main and side branches appeared unacceptable.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Japan; Kaplan-Meier Estimate; Myocardial Ischemia; Registries; Risk Factors; Sirolimus; Treatment Outcome

There is limited evidence on the medium-term prognosis of patients with chronic total occlusion successfully treated with drug-eluting stent (DES) implantation.. We compared the medium-term outcome of 111 patients with chronic total occlusion (CTO) successfully treated with implantation of sirolimus-or paclitaxel-eluting stents versus 112 patients treated with bare metal stents.. During an overall follow-up period of 18 months, the composite endpoint of death, myocardial infarction or target lesion revascularization was significantly lower in the drug-eluting stent than in the bare metal stent group: 8.1% vs. 21.6%, respectively (p=0.005). The difference was due to the reduction of target lesion revascularization with DES compared to bare metal stents: 3.6% vs. 18.9%, respectively (p<0.001). The Cox proportional hazards model identified DES as an independent predictor of adverse cardiac events (adjusted hazard ratio, 0.16; 95% confidence interval 0.05 to 0.52, p=0.002).. During medium-term follow-up use of DES is associated with improved outcome compared to use of bare metal stents in patients with CTO.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Chronic Disease; Coronary Angiography; Coronary Occlusion; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Prognosis; Proportional Hazards Models; Retrospective Studies; Sirolimus; Stents; Treatment Outcome

In the ABSORB trial, the feasibility of using a fully bioabsorbable everolimus-eluting stent (BVS; Abbott Vascular, Santa Clara, CA) in patients with ischemia and a single de novo coronary lesion was investigated. Some important concerns about the efficacy of this device were raised by this study. The in-stent late loss with the BVS (0.44 mm) was comparable to that seen with some drug-eluting stents currently on the market, and the late lumen loss was primarily due to reduction in stent area. Technical improvements aimed at definitively preventing late vessel recoil and negative remodeling, as well as clarification of the behavior of these devices with longer follow-up, are needed before fully bioabsorbable drug-eluting stents can be considered a therapeutic option for patients with coronary artery disease.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Ischemia; Prosthesis Design; Research Design; Sirolimus; Treatment Outcome

Topics: Data Interpretation, Statistical; Drug-Eluting Stents; Humans; Myocardial Ischemia; Paclitaxel; Research Design; Sirolimus; Treatment Outcome

Little is known about the impact of psychological risk factors on cardiac prognosis in the drug-eluting stent era. We examined whether the distressed personality (Type D) moderates the effect of percutaneous coronary intervention with sirolimus-eluting stent implantation on adverse clinical events at 2-year follow-up. Type D is an emerging risk factor in patients with cardiovascular disease.. Prospective follow-up study.. Three hundred and fifty-eight patients with ischemic heart disease, who consecutively underwent percutaneous coronary intervention with sirolimus-eluting stent as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital registry, completed the Type D Scale (DS14) post-percutaneous coronary intervention (PCI). The end-point was a composite of death and non-fatal myocardial infarction 2 years after PCI.. At follow-up, there were 22 events (12 deaths and 11 myocardial infarctions). Type D patients had a greater than two-fold risk of an event at follow-up compared with non-Type D patients (10.4 vs. 4.4%, P=0.031). In multivariable analysis, Type D remained an independent predictor of adverse outcome (hazard ratio: 2.61; 95% confidence interval: 1.12-6.09; P=0.027) adjusting for sex, age, and history of coronary artery disease, multivessel disease, diabetes, hypercholesterolemia, hypertension, renal impairment and smoking. Previous cardiac history was also an independent predictor of death or myocardial infarction (hazard ratio: 2.83; 95% confidence interval: 1.00-7.96; P=0.049).. Type D personality moderated the effect of percutaneous coronary intervention on hard clinical events despite treatment with the latest innovation in interventional cardiology. The inclusion of psychological risk factors in general and personality factors in particular may optimize risk stratification in the drug-eluting stent era.

Topics: Angioplasty, Balloon, Coronary; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Personality; Prognosis; Prospective Studies; Registries; Risk Assessment; Risk Factors; Sirolimus; Stents; Surveys and Questionnaires; Treatment Outcome

Limited information is available regarding restenosis after implantation of a sirolimus-eluting stent (SES).. To report on angiographic characteristics, clinical presentation and treatment of this particularly complex type of coronary lesion.. A total of 1424 SES were implanted in 1159 patients (average 1.2 per patient) for chronic or acute coronary syndromes in the University Hospital of Siena (Siena, Italy), which is a tertiary centre. Symptomatic in-SES restenosis was observed in 26 patients (2.2%) at 10+/-5 months (median eight months, range four to 23 months) following the initial intervention. In-SES restenosis was associated with stable angina in 16 patients, acute myocardial infarction in three patients and unstable angina in seven patients. Two patients had restenosis in two separate SES. Conditions often associated with in-SES restenosis included treatment of chronic total occlusion, geographic miss or in-stent restenosis during the index procedure. Among the first 20 patients, those with focal, in-body SES (type Ic) restenosis received balloon-only angioplasty, and patients with other patterns received repeat SES implantation. Clinical and angiographic follow-up (average 16+/-7 months) recorded one death (noncardiac) in the balloon-only group and four cases of unstable angina (three due to relapsing in-SES restenosis in the balloon-only group and the fourth due to a de novo lesion). Follow-up quantitative angiography showed a higher incidence of binary restenosis after balloon-only treatment (57% versus 17%; P<0.05), as well as higher lumen loss and loss index (P<0.05).. Restenosis after SES implantation occurs more commonly in a focal pattern in-body or at the proximal edge of the stent. Repeat SES implantation appears to be a safer and more effective therapeutic choice than balloon-only angioplasty.

Topics: Aged; Angioplasty, Balloon, Coronary; Equipment Failure; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Radiography; Retrospective Studies; Sirolimus; Stents; Treatment Outcome

Sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) both significantly reduce the need for repeat intervention compared to bare metal stents. Studies comparing the clinical outcomes of these stents in noncomplex subsets of patients and lesions demonstrate a similar safety and efficacy profile. The data for more complex subsets of patients and lesions remains conflicting. This study aimed to compare SES with PES in a selected population with a broad range of complex features.. The patient population consisted of 1,591 consecutive patients with complex features undergoing drug-eluting stent (DES) implantation. In the SES group there were 1,095 patients (1,653 lesions) and in the PES group 496 patients (802 lesions). In-hospital, 30-day, and 12-month clinical outcomes were compared between groups. No discernable difference in major adverse cardiac events (MACE) between SES and PES was detected at intermediate and longer-term follow-up (SES 22.4% vs. PES 20.5% at 12 months; P=0.407). A trend toward increased angiographically documented stent thrombosis was observed in the SES group at both 3 and 12 months (SES 2.2% vs. PES 0.8% at 12 months; P=0.051). When adopting the more inclusive definition of probable stent thrombosis, this trend was no longer seen. After adjusting for baseline differences between the two groups, there still remained no difference in MACE between SES and PES (HR 1.051 [CI 0.826-1.339] P=0.685). The trend toward increased angiographically documented stent thrombosis in the SES group remained after adjustment for baseline differences (HR 2.836 [CI 0.968-8.311] P=0.057).. In a selected population with complex disease the rate of MACE was comparable between SES and PES, with higher overall rates of thrombosis and MACE compared to a noncomplex population. Thus, the focus should be directed to prevent late complications in this complex subset regardless of stent type selection.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Proportional Hazards Models; Prosthesis Design; Research Design; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome

Many interventional treatments have been proposed for intrastent stenosis, in particular by drug-eluting stents, with encouraging results. The aim of this study was to assess the clinical outcome of patients with restenosis of an ordinary uncovered stent treated by a drug eluting stent in a prospective series. The register included 43 patients (50 intrastent restenoses) treated by a drug eluting stent (Cypher or Taxus). The restenosis lesion was focal in 32% of cases with an average length of 14.8 +/- 8 mm and diameter inferior to 2.5 mm in 48% of cases. A Cypher stent was implanted in 44% of cases and a Taxus stent in 56% of cases. After an average follow-up of 6.7 +/- 1.3 months, the major adverse cardiac event rate was 9.3%. It included one transmural infarct in a patient, due to stent thrombosis, and symptomatic restenoses in 3 patients (clinical restenosis rate: 7%). An angiographic control was performed in 15 patients (35%) identifying focal restenosis at the exit of the stent in the 3 symptomatic patients. As in previously reported studies, these results show that with well conducted platelet antiaggregant therapy, the treatment of intrastent restenosis with a drug eluting stent is effective with a low rate of adverse cardiovascular events which compares favourably with previously proposed techniques of management.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Aspirin; Clopidogrel; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Equipment Design; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Paclitaxel; Platelet Aggregation Inhibitors; Prospective Studies; Sirolimus; Stents; Surface Properties; Ticlopidine; Treatment Outcome

We sought to determine whether nonresponsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis.. No data exist about the impact of nonresponsiveness to clopidogrel on the risk of DES thrombosis.. We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 mumol adenosine 5'-diphosphate > or =70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up.. The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041).. Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.

Topics: Adult; Antineoplastic Agents, Phytogenic; Blood Platelets; Clopidogrel; Comorbidity; Female; Humans; Immunosuppressive Agents; Male; Multivariate Analysis; Myocardial Ischemia; Paclitaxel; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Sirolimus; Stents; Thrombosis; Ticlopidine

Topics: Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Bypass; Humans; Myocardial Ischemia; Paclitaxel; Patient Selection; Prosthesis Design; Radiography; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

We compared the outcome of drug eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction with the outcome of a similar group of patients undergoing coronary artery by-pass grafting (CABG).. Revascularization provides long-term benefits in patients with severe LV dysfunction. However the modality to achieve it is still unsettled in this high risk group of patients.. Two-hundred-twenty patients (20% women) with severe LV dysfunction (LV Ejection Fraction

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Bypass; Female; Follow-Up Studies; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Retrospective Studies; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; United States; Ventricular Dysfunction, Left

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Humans; Myocardial Ischemia; Paclitaxel; Patient Selection; Prosthesis Design; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Thrombosis; Treatment Outcome

Lately drug-eluting stents (DES) have dramatically reduced restenosis rates and need for repeat revascularization in a wide subset of lesion and patients. However, their benefit for the treatment of large vessels (> 3.0 mm) has yet to be established.. We investigated whether DES are superior to bare metal stents (BMS) in terms of clinical outcomes for the treatment of large coronary vessels.. This study assessed the long-term outcomes (cardiac death, acute myocardial infarction, and need for repeat intervention in the treated vessel) of patients treated with either a DES (Cypher and Taxus) or a BMS of > or = 3.5 mm in diameter. A total of 250 consecutive patients who underwent DES implantation were clinically followed for 1 year and compared to 250 patients who were treated with BMS. Interventions in the setting of acute ST elevation myocardial infarction and treatment of bypass grafts were excluded.. Cypher was the DES deployed in 70.8% of cases. Most of the enrolled patients were men (78%) with single vessel disease (65.6%). The left anterior descending artery was the culprit vessel in 34.2% of cases. Bare metal stent and DES cohorts had equivalent interpolated reference vessel diameter (3.19 +/- 0.3 mm for BMS vs 3.18 +/- 0.2 for DES; P = .1). Lesion was significantly longer in the group treated with DES (13.4 +/- 5.1 mm for BMS group vs 14.3 +/- 3.5 for DES; P = .0018). After 1 year of clinical follow-up, 95.2% of patients treated with DES and 91.2% of the patients who received BMS were free of major events (P = .2). A trend toward higher target-lesion revascularization was noticed in the group treated with BMS (4.8% vs 1.6%; P = .07).. Percutaneous treatment of large coronary vessels carries a low risk of clinical events irrespective of the type of stent used.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Stenosis; Coronary Vessels; Drug Delivery Systems; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Sirolimus; Stents

The anesthetic noble gas, xenon, produces cardioprotection. We hypothesized that other noble gases without anesthetic properties [helium (He), neon (Ne), argon (Ar)] also produce cardioprotection, and further hypothesized that this beneficial effect is mediated by activation of prosurvival signaling kinases [including phosphatidylinositol-3-kinase, extracellular signal-regulated kinase, and 70-kDa ribosomal protein s6 kinase] and inhibition of mitochondrial permeability transition pore (mPTP) opening in vivo.. Rabbits (n = 98) instrumented for hemodynamic measurement and subjected to a 30-min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion received 0.9% saline (control), three cycles of 70% He-, Ne-, or Ar-30% O2 administered for 5 min interspersed with 5 min of 70% N2-30% O2 before LAD occlusion, or three cycles of brief (5 min) ischemia interspersed with 5 min reperfusion before prolonged LAD occlusion and reperfusion (ischemic preconditioning). Additional groups of rabbits received selective inhibitors of phosphatidylinositol-3-kinase (wortmannin; 0.6 mg/kg), extracellular signal-regulated kinase (PD 098059; 2 mg/kg), or 70-kDa ribosomal protein s6 kinase (rapamycin; 0.25 mg/kg) or mPTP opener atractyloside (5 mg/kg) in the absence or presence of He pretreatment.. He, Ne, Ar, and ischemic preconditioning significantly (P < 0.05) reduced myocardial infarct size [23% +/- 4%, 20% +/- 3%, 22% +/- 2%, 17% +/- 3% of the left ventricular area at risk (mean +/- sd); triphenyltetrazolium chloride staining] versus control (45% +/- 5%). Wortmannin, PD 098059, rapamycin, and atractyloside alone did not affect infarct size, but these drugs abolished He-induced cardioprotection.. The results indicate that noble gases without anesthetic properties produce cardioprotection by activating prosurvival signaling kinases and inhibiting mPTP opening in rabbits.

Topics: Androstadienes; Animals; Argon; Atractyloside; Cardiotonic Agents; Disease Models, Animal; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Heart Ventricles; Helium; Ischemic Preconditioning, Myocardial; Male; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Neon; Noble Gases; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors; Protein Kinases; Rabbits; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Sirolimus; Wortmannin

Patients older than 75 years undergoing percutaneous coronary interventions are at increased risk for major adverse cardiac events strongly influenced by comorbidities. In various randomized trials, sirolimus-eluting stent (SES) implantation has been shown to decrease the incidence of in-stent restenosis and to reduce repeat revascularization regardless of patient age.. The present study evaluates the outcome after SES implantation in 954 patients older than 75 years compared with 5801 patients younger than 75 years enrolled in the German Cypher Registry in a routine clinical setting.. The elderly were at higher risk regarding renal failure, diabetes, hypertension, impaired left ventricular function, and 3-vessel disease. The SES implantation resulted in an impressive relief of angina. As expected, in-hospital and 6-month mortality rates were higher in the elderly. However, there was no difference with respect to the rate of major adverse cardiac events (death, myocardial infarction, ischemia-driven target vessel revascularization) at 6-month follow-up.. Nonfatal complications such as myocardial infarction or repeat target vessel revascularization did not increase with age, even taking patients older than 80 years into account.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Comorbidity; Coronary Restenosis; Female; Germany; Hospital Mortality; Humans; Immunosuppressive Agents; Male; Multivariate Analysis; Myocardial Ischemia; Prospective Studies; Registries; Sirolimus; Stents; Treatment Outcome

Interventional cardiology is a rapidly changing area, with technical improvements allowing us to treat an increasing number of clinical situations by percutaneous methods. Indeed, the interface between interventional cardiologist and cardiac surgeon has changed in the past decade, with a dramatic reduction in the need for "rescue" surgery. The most significant recent development has been drug-eluting stents, which have dramatically reduced the rates of restenosis, although at the cost of a need for longer-term antiplatelet therapy after implantation. Failure to continue this antiplatelet therapy may lead to a small but significant excess of stent thrombosis. There have been many other technological improvements, such as distal protection devices and better guidewires for crossing occluded vessels, as well as percutaneous devices for treating valve disease and other structural cardiac abnormalities. These technologies are often best developed in a combined approach with cardiac surgeons, and the selection of the best treatment more than ever requires close cooperation between cardiologist and surgeon.

Topics: Angioplasty, Balloon, Coronary; Cardiology; Coronary Artery Bypass; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Myocardial Ischemia; Sirolimus; Stents; Treatment Failure; United States

Stents were implanted to 554 previously non-revascularized patients in 703 injured coronary segments; 32% of stented stenoses were complicated; 23% of patients received 2-4 stents. Immediate success was 100% with no cases of acute stent thrombosis. Rate of in-hospital subacute thrombosis and non-Q-wave myocardial infarction was 0.2%. Survival without restenosis, angina, myocardial infarction and repeat revascularization during follow up (mean duration 257+/-107 days) was 94%, restenosis rate -- 5.6%. Six patients with in-stent restenosis were successfully revascularized. All 108 patients followed for 27 months were alive by the end of this term.

Topics: Adult; Aged; Aged, 80 and over; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Inpatients; Male; Middle Aged; Myocardial Ischemia; Prosthesis Design; Retrospective Studies; Sirolimus; Stents; Time Factors; Treatment Outcome

The risk of Kaposi's sarcoma (KS) is increased after organ transplantation. Management of KS in the cardiac transplant population may be difficult because reduction of immunosuppression is often not practical. This report describes a case of KS occurring in the early post-transplant period. Modification of immunosuppression with the use of sirolimus led to tumor regression for 24 months, but with subsequent localized progression of disease.

Topics: Adult; Heart Transplantation; Herpesvirus 8, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Lung Neoplasms; Male; Myocardial Ischemia; Postoperative Period; Sarcoma, Kaposi; Sirolimus

We examined the efficacy of drug-eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction and compared the outcome with a similar group of patients undergoing bare metal stent (BMS) implantation.. Patients with severe LV dysfunction are a high risk group. DES may improve the long term outcomes compared with BMS.. One hundred and ninety one patients (23% women) with severe LV dysfunction (LV ejection fraction < or =35%) underwent coronary stent implantation between May 2002 and May 2005 and were available for follow-up. One hundred and twenty eight patients received DES (Sirolimus in 72 and Paclitaxel in 54) and 63 patients had BMS. Patients with acute S-T elevation myocardial infarction (STEMI) were excluded. The primary endpoint was cardiovascular mortality. A composite endpoint of major adverse cardiac events (MACE) including cardiovascular mortality, myocardial infarction (MI), and target vessel revascularization (TVR) was the secondary endpoint.. Mean follow-up was 420 +/- 271 days. No differences were noted in age (69 +/- 10 years vs. 70 +/- 10 years, P = NS), number of vessel disease (2.3 +/- 0.7 vs. 2.2 +/- 0.8, P = NS), history of congestive heart failure (47% vs. 46%, P = NS), MI (60% vs. 61%, P = NS), or number of treated vessels (1.3 +/- 0.5 vs. 1.3 +/- 0.6, P = NS) for the DES and BMS group, respectively. Diabetes was more common among DES patients (45% vs. 25%, P = 0.01). The left ventricular ejection fraction (LVEF) was similar between the two groups (28% +/- 6% vs. 26% +/- 8%, P = NS for the DES and BMS, respectively). During the follow-up, there were a total of 25 deaths of which two were cancer related (2 in DES group). There were 23 cardiac deaths, 8/126 (6%) which occurred in the DES group and 15/63 (24%) in the BMS group (P = 0.05 by log-rank test). MACE rate was 10% for the DES group and 41% for the BMS group (P = 0.003). NYHA class improved in both groups (from 2.5 +/- 0.8 to 1.7 +/- 0.8 in DES and from 2 +/- 0.8 to 1.4 +/- 0.7 in the BMS, P = NS).. Compared with bare-metal stents, DES implantation reduces mortality and MACE in high risk patients with severe left ventricular dysfunction.

Topics: Aged; Aged, 80 and over; Blood Vessel Prosthesis Implantation; Cardiomyopathies; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Severity of Illness Index; Sirolimus; Stents; Stroke Volume; Survival Rate; Treatment Outcome; United States; Ventricular Dysfunction, Left

The study was aimed to identify factors affecting sirolimus apparent clearance (CL/F) in de novo heart transplant recipients using a population pharmacokinetic approach. A total of 31 patients (7 female and 24 male) originally included in a formal clinical trial, contributed 524 sirolimus blood concentrations with the time after dose ranging from 11.08 to 31.83 hours. Sirolimus concentrations were measured using liquid chromatography-tandem mass spectrometry and data analysis was carried out using NONMEM (Globomax LLC, Hanover, MD) software. Factors screened included age, weight, gender, primary diagnosis, biochemical and hematological indices, cyclosporine dose, days post-transplant and potential interacting medications. The predictive performance of the final model was evaluated using a data-splitting method. Sirolimus apparent clearance (CL/F) was decreased by 20.8% for every 100 mg increase in cyclosporine daily dose and was 62.1% lower in patients with primary diagnosis of ischemic heart disease (IHD). Sirolimus apparent clearance was 37.8% lower when triglyceride was greater than 2 mmol/L. Based on the final model, the average values for sirolimus CL/F and apparent volume of distribution were 7.09 and 1350 L/h, respectively. Inter-subject variability in CL/F was 27.5% and residual random error was 24.1%. This study identified cyclosporine dose, hypertriglyceridemia and primary diagnosis of IHD as the most important factors affecting sirolimus CL/F. This information may assist in dose individualization of sirolimus in heart transplant recipients.

Topics: Adolescent; Adult; Aged; Cholesterol, HDL; Female; Half-Life; Heart Transplantation; Humans; Lipids; Male; Middle Aged; Models, Biological; Myocardial Ischemia; Sirolimus; Triglycerides

We sought to describe the incidence of late angiographic stent thrombosis (LAST) events in an unselected drug-eluting stent (DES) population.. Concerns have been raised that LAST may be a potential limitation of DES.. We have previously reported the angiographic incidence of early stent thrombosis (1.0%) in this prospective cohort of 2,006 patients treated with either sirolimus-eluting stents (SES) (n = 1,017) or paclitaxel-eluting stents (PES) (n = 989). We continued long-term follow-up to determine the incidence of LAST events, defined as angiographically proven stent thrombosis associated with acute symptoms more than 30 days after DES implantation. All patients had at least 1 year of follow-up, mean duration 1.5 years.. There were eight angiographically confirmed LAST events in seven patients: three with SES (at 2, 25, and 26 months) and five with PES (at 6, 7, 8, 11, and 14.5 months). Three cases were related to complete cessation of antiplatelet therapy, two cases occurred while patients were on aspirin therapy within one month of cessation of clopidogrel, and three cases occurred at a time when patients were apparently clinically stable on aspirin monotherapy. We observed no cases of LAST in patients who were on dual antiplatelet therapy. Two deaths occurred directly as a result of LAST.. Angiographically proven late stent thrombosis occurs with an incidence of at least 0.35% (95% confidence limits 0.17% to 0.72%) in patients treated with DES. Importantly, it may also occur when patients are stable on antiplatelet monotherapy.

Topics: Adult; Aged; Blood Vessel Prosthesis Implantation; Coronary Thrombosis; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Radiography; Sirolimus; Stents; Time Factors

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Bypass; Coronary Restenosis; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Risk Factors; Sirolimus; Stents; Time Factors

Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia-inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF-1 activity depends on the amount of HIF-1alpha subunit, which is tightly regulated by the oxygen tension. In the myocardium, VEGF expression has been shown to be induced under nonhypoxic conditions by mechanical stresses. However, the cellular mechanism of stress-mediated VEGF induction remains unclear. Therefore, we examined the possible involvement of HIF-1 in stress-mediated VEGF induction in rat hearts. In this study, we increased the left ventricular wall tension using 3 different methods, namely by inducing regional ischemia, by expanding an intraventricular balloon, and by producing hemodynamic overload using an aortocaval shunt. In all cases, HIF-1alpha accumulated in the nuclei of cardiac myocytes in the early phase, and this was followed by VEGF induction. Phosphatidylinositol 3-kinase (PI3K)-dependent Akt phosphorylation was found to be activated by mechanical stress and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the stress-mediated induction of HIF-1alpha and VEGF was suppressed by gadolinium (a stretch-activated channel inhibitor), wortmannin, and rapamycin (a FRAP inhibitor). Our results suggest that HIF-1alpha plays an important role in the induction of VEGF in nonischemic and mechanically stressed myocardium, and that this is regulated by stretch-activated channels and the PI3K/Akt/FRAP pathway. Moreover, this signaling pathway, which induces HIF-1alpha, seems to play an important role in the adaptation of the myocardium to stresses. The full text of this article is available at http://www.circresaha.org.

Topics: Androstadienes; Animals; Cell Nucleus; Endothelial Growth Factors; Enzyme Inhibitors; Gadolinium; Gene Expression Regulation; Hypoxia-Inducible Factor 1, alpha Subunit; In Vitro Techniques; Ion Channels; Lymphokines; Male; Myocardial Ischemia; Myocardium; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Sirolimus; Specific Pathogen-Free Organisms; Stress, Mechanical; Transcription Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Ventricular Function, Left; Wortmannin