sirolimus and Diabetic-Angiopathies

We performed this meta-analysis to determine which stent among everolimus eluting stents (EES), sirolimus eluting stents (SES) and paclitaxel eluting stents (PES) should be preferred for the treatment of DM patients.. A systematic search of publications about randomized controlled trials (RCTs) focused on diabetic patients received EES, SES or PES was conducted. We evaluated the following indicators: target vessel revascularization (TVR), target lesion revascularization (TLR), late luminal loss (LLL), stent thrombosis (ST), myocardial infarction (MI), all-cause mortality and cardiac mortality.. EES showed obvious advantages over SES for DM patients, as it induced the lowest rate of target vessel revascularization and target lesion revascularization (TLR) (p = 0.04). In addition, EES induced lower in-segment LLL than PSE and SES and lower in-stent LLL than PES in DM patients (all p < 0.05). Moreover, EES effectively reduced all-cause mortality compared to SES (RR = 0.71, 95% CI: 0.52-0.99, p = 0.04) and MI rates compared to PES (RR = 0.44, 95% CI: 0.26-0.73, p = 0.0002). Furthermore, EES could reduce the ST rate compared with both SES (RR = 0.53, 95% CI: 0.28-0.98, p = 0.04) and PES (RR = 0.18, 95% CI: 0.07-0.51, p = 0.001).. Among those three types of stents, EES should be the first recommended stent for DM patients.

Topics: Cardiovascular Agents; Diabetic Angiopathies; Diabetic Cardiomyopathies; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Treatment Outcome

This review article aims to summarize the findings of the most relevant research that compared the use of paclitaxel vs. "limus" based drug eluting stent (DES) in diabetic patients and to define the current state of knowledge with new stent technologies in this patient population.. Since drug eluting stents (DES) were introduced, it has been of great interest to establish whether paclitaxel or sirolimus eluting stents have the same safety and efficacy features for patients with coronary artery disease. The answer to this question is particularly relevant for diabetic patients. Several randomized trials, registry-based studies, and meta-analyses have assessed the performance of these different DES in diabetic patients. The most recently published data favors limus over paclitaxel DES in diabetic patients, but most of these studies compared first vs. second generation DES with the inherent caveats of comparing different platforms, alloys, and drug delivery vehicles. In this literature review, we found that there is robust evidence favoring the use of DES over bare metal stents in diabetic patients with coronary artery disease. We also found that the current state of knowledge is that the everolimus eluting stents have better safety and efficacy than paclitaxel eluting stents in diabetic patients and hence should be the preferred choice. New revascularization strategies including bio-absorbable scaffolds, polymer free stents, and bio-degradable polymers are being studied in diabetic patients with encouraging results.

Topics: Coronary Disease; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Treatment Outcome

This study aimed to compare 6 months to 5 years stent thrombosis (ST) and adverse cardiovascular outcomes associated with sirolimus-eluting stents (SES) and other drug-eluting stents (DES) in patients with type 2 diabetes mellitus (T2DM).Electronic databases were searched for studies comparing SES with other DES in patients with T2DM. Total ST, definite ST, probable ST, and other adverse cardiovascular outcomes reported between 6 months and 5 years were considered as the clinical end points in this study. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for categorical variables and the pooled analyses were performed with RevMan 5.3 software.Twenty-nine studies involving a total number of 25,729 patients with diabetes were included in this meta-analysis. SES were not associated with significantly higher total, definite, and probable STs with OR: 0.95, 95% CI: 0.77-1.17, P = 0.62; OR: 0.94, 95% CI: 0.65-1.37, P = 0.76; and OR: 1.05, 95% CI: 0.77-1.45, P = 0.74, respectively. SES were also noninferior to the other non-sirolimus eluting drug eluting stents (non-SE DES) in terms of all-cause mortality, cardiac death, myocardial infarction, and stroke with OR: 0.92, 95% CI: 0.82-1.03, P = 0.16; OR: 1.09, 95% CI: 0.88-1.35, P = 0.44; OR: 0.92, 95% CI: 0.80-1.06, P = 0.26; and OR: 0.79, 95% CI: 0.49-1.28, P = 0.43, respectively. Target vessel revascularization, target lesion revascularization, and major adverse cardiac events were also similarly reported between SES and non-SE DES with OR: 1.04, 95% CI: 0.83-1.31, P = 0.72; OR: 1.25, 95% CI: 0.95-1.64, P = 0.11; and OR: 1.06, 95% CI: 0.90-1.25, P = 0.49, respectively.During this particular follow-up period, SES were not associated with any increase in ST among these patients with T2DM. Mortality and other adverse cardiovascular outcomes were also not significantly different between these 2 groups. Hence, SES should be considered neither superior nor inferior to other DES. They are expected to be equally effective and safe to use in patients with T2DM.

Topics: Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

Diabetes mellitus is a metabolic homeostasis disease that contributes to additional comorbidities such as cardiovascular disease (CVD) and cancer. It has a long undiagnosed latent period during which there can be irreparable damage to the pancreas and cardiovascular tissues. Recent studies have highlighted the roles of several microRNAs in CVD. Determining the microRNAs that link diabetes mellitus and CVD is an important topic to be explored. In the present review, we discuss the microRNAs that contribute to the progression of diabetes mellitus and CVD and focus on the miR-29 family microRNAs whose expression is upregulated by hyperglycemia and proinflammatory cytokines, the hallmarks of diabetes mellitus. Upregulation of miR-29 expression is a key factor in the loss of pancreatic β cells and development of the first stage of type 1 diabetes mellitus (T1DM). Additionally, miR-29-mediated suppression of myeloid cell leukemia 1 (MCL-1), an important prosurvival protein, underlies Marfan's syndrome, abdominal aortic aneurysm, and diabetes mellitus-associated cardiomyocyte disorganization. Suppression of miR-29 expression and subsequent increase in the prosurvival MCL-1, however, promotes tumor development. Therefore, miR-29 mimics that suppress MCL-1 are hailed as tumor suppressors. The critical question is whether an increase in miR-29 levels is well tolerated in conditions of comorbidities in which insulin resistance is an underlying disease. In light of increasing awareness of the interconnection of diabetes mellitus, CVD, and cancer, it is of utmost importance to understand the mechanism of action of current treatment options on all of the comorbidities and careful evaluation of cardiovascular toxicity must accompany any treatment paradigm that increases miR-29 levels.

Topics: Animals; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Immunosuppressive Agents; MicroRNAs; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasms; Sirolimus

The aim of this study was to evaluate 1-year clinical outcomes of diabetic patients treated with the Absorb bioresorbable vascular scaffold (BVS).. Clinical outcomes of diabetic patients after BVS implantation have been unreported.. This study included 101 patients in the ABSORB Cohort B trial and the first consecutive 450 patients with 1 year of follow-up in the ABSORB EXTEND trial. A total of 136 diabetic patients were compared with 415 nondiabetic patients. In addition, 882 diabetic patients treated with everolimus-eluting metal stents (EES) in pooled data from the SPIRIT trials (SPIRIT FIRST [Clinical Trial of the Abbott Vascular XIENCE V Everolimus Eluting Coronary Stent System], SPIRIT II [A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System], SPIRIT III [Clinical Trial of the XIENCE V Everolimus Eluting Coronary Stent System (EECSS)], SPIRIT IV Clinical Trial [Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System]) were used for the comparison by applying propensity score matching. The primary endpoint was a device-oriented composite endpoint (DoCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization at 1-year follow-up.. The cumulative incidence of DoCE did not differ between diabetic and nondiabetic patients treated with the BVS (3.7% vs. 5.1%, p = 0.64). Diabetic patients treated with the BVS had a similar incidence of the DoCE compared with diabetic patients treated with EES in the matched study group (3.9% for the BVS vs. 6.4% for EES, p = 0.38). There were no differences in the incidence of definite or probable scaffold/stent thrombosis (0.7% for both diabetic and nondiabetic patients with the BVS; 1.0% for diabetic patients with the BVS vs. 1.7% for diabetic patients with EES in the matched study group).. In the present analyses, diabetic patients treated with the BVS showed similar rates of DoCEs compared with nondiabetic patients treated with the BVS and diabetic patients treated with EES at 1-year follow-up. (ABSORB Clinical Investigation, Cohort B; NCT00856856; ABSORB EXTEND Clinical Investigation; NCT01023789; Clinical Trial of the Abbott Vascular XIENCE V Everolimus Eluting Coronary Stent System [SPIRIT FIRST]; NCT00180453; A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System [SPIRIT II]; NCT00180310; Clinical Trial of the XIENCE V Everolimus Eluting Coronary Stent System [EECSS] [SPIRIT III]; NCT00180479; Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System [SPIRIT IV Clinical Trial]; NCT00307047).

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Chi-Square Distribution; Clinical Trials as Topic; Coronary Stenosis; Coronary Thrombosis; Diabetic Angiopathies; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Propensity Score; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

To compare by meta-analysis the efficacy and safety of sirolimus-eluting and bare-metal stents in coronary artery disease (CAD) patients with diabetes.. PubMed, MEDLINE and EMBASE were searched from 1971 to 2012. Data on the efficacy and safety of sirolimus-eluting and bare-metal stents in patients with diabetes were collected. A meta-analysis was then performed on a total of 1 259 CAD patients with diabetes from six studies. The odds ratio (OR) was used for comparison. Subgroup analysis was performed according to the sample size, year of study, subjects' geographic area and study method.. Compared with those in the bare-metal stent group (BMS), the subjects in the sirolimus-eluting stent (SES) group had a reduced risk for major cardiac events [OR 0.42, 95% confidence interval (CI): 024-0.74, p < 0.01] and target-lesion revascularisation (OR 0.26, 95% CI: 0.11 - 0.59, p < 0.01). There was no difference for myocardial infarction (OR 0.92, 95% CI: 0.61-1.40, p > 0.05) or mortality (OR 1.19, 95% CI: 0.74-1.92, p > 0.05). Subgroup analysis showed a significant difference for overall risk of major cardiac events between SES and BMS when the sample size was ≤ 90 (OR 0.28, 95% CI: 0.16-0.48, p < 0.01), when it was a randomised control trial (RCT) (OR 0.28, 95% CI: 0.19-0.42, p < 0.01), or when it was performed on European subjects (OR 0.45, 95% CI: 0.27-0.77, p < 0.01). The sensitivity was not different when one study was removed at a time.. Our study confirmed that SES are safer and more effective than BMS in CAD patients with diabetes, as far as major cardiac events are concerned.

Topics: Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Metals; Myocardial Infarction; Odds Ratio; Patient Safety; Patient Selection; Percutaneous Coronary Intervention; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Stents; Treatment Outcome

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

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

Some (but not all) prior trials have reported differential outcomes after percutaneous coronary intervention with paclitaxel-eluting stents versus stents eluting rapamycin analogs according to the presence of diabetes mellitus. These studies lacked sufficient power to examine individual safety and efficacy end points.. To determine whether an interaction exists between the presence of diabetes mellitus and treatment with everolimus-eluting stents compared with paclitaxel-eluting stents, we pooled the databases from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions (SPIRIT) II, SPIRIT III, SPIRIT IV, and A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice (COMPARE) trials in which percutaneous coronary intervention was performed in 6780 patients, 1869 (27.6%) of whom had diabetes mellitus. Patients without diabetes mellitus treated with everolimus-eluting stents compared with paclitaxel-eluting stents had significantly reduced 2-year rates of mortality (1.9% versus 3.1%; P=0.01), myocardial infarction (2.5% versus 5.8%; P<0.0001), stent thrombosis (0.3% versus 2.4%; P<0.0001), and ischemia-driven target lesion revascularization (3.6% versus 6.9%; P<0.0001). In contrast, among patients with diabetes mellitus, there were no significant differences between the 2 stent types in any measured safety or efficacy parameter. Significant interactions were present between diabetic status and stent type for the 2-year end points of myocardial infarction (P=0.01), stent thrombosis (P=0.0006), and target lesion revascularization (P=0.02).. We have identified a substantial interaction between diabetes mellitus and stent type on clinical outcomes after percutaneous coronary intervention. In patients without diabetes mellitus, everolimus-eluting stents compared with paclitaxel-eluting stents resulted in substantial 2-year reductions in death, myocardial infarction, stent thrombosis, and target lesion revascularization, whereas no significant differences in safety or efficacy outcomes were present in diabetic patients.

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Tubulin Modulators

There is an ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. We addressed this issue by making a synthesis of the available evidence on the relative long-term efficacy and safety of sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) in these patients.. Individual patient data were analyzed from 6 randomized trials specifically designed to compare SES with PES in diabetic patients. In total, 1183 patients were followed up for a median of 3.9 years (25th, 75th percentiles 3.4-4.5 years). The primary efficacy end point was target lesion revascularization (TLR). The composite of death and myocardial infarction (MI) was the primary safety end point. Stent thrombosis was a secondary end point. Overall hazard ratios (HRs) with 95% CIs were calculated as summary estimates.. No significant heterogeneity was seen across the 6 randomized trials for all analyzed events. Sirolimus-eluting stent was associated with a significant reduction in the risk of TLR (HR 0.65 [0.47-0.91], P = .01). No significant differences were observed regarding the risk of death or MI (HR 1.04 [0.74-1.45], P = .83) and stent thrombosis (HR 1.00 [0.31-3.30], P = .67). Mortality was also not affected by the type of DES (HR 0.95 [0.65-1.39], P = .79).. In diabetic patients with coronary artery disease, SES leads to a sustained reduction in the risk of TLR compared with PES. Both these DES types are, however, comparable with respect to the risk of stent thrombosis, MI, or death over long-term follow-up.

Topics: Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus

The performance of drug-eluting stents (DESs) in high-risk patients with diabetes and acute ST-elevation myocardial infarction (STEMI) who have undergone primary angioplasty has not been previously studied. The objective was to evaluate the efficacy and safety of DESs in diabetic patients with STEMI.. We performed a pooled analysis of individual patient data from seven randomized trials that compared DESs (i.e., sirolimus- or paclitaxel-eluting stents) with bare-metal stents (BMSs) in patients with STEMI. The analysis involved 389 patients with diabetes mellitus from a total of 2476 patients. The outcomes of interest were target-lesion revascularization, stent thrombosis, death and the composite endpoint of death or recurrent myocardial infarction during a follow-up of 12-24 months.. Overall, 206 diabetic patients received a DES and 183, a BMS. The risk of target-lesion revascularization was significantly lower in patients treated with a DES compared to those treated with a BMS (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.23-0.88; P=.02). There was no significant difference in the risk of stent thrombosis between those treated with a DES or a BMS (HR 0.33, 95% CI 0.09-1.13; P=.08). Similarly, the risk of the combined endpoint of death or myocardial infarction was not significantly different between patients treated with a DES or a BMS (HR 0.64, 95% CI 0.36-1.13; P=.12).. Compared with BMSs, DES use improved clinical outcomes in diabetic patients undergoing primary angioplasty for STEMI: the need for reintervention was reduced, with no increase in mortality or myocardial infarction.

Topics: Aged; Antineoplastic Agents, Phytogenic; Diabetic Angiopathies; Drug-Eluting Stents; Electrocardiography; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

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

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

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

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

Patients with type 2 diabetes mellitus represent the 25% of those requiring myocardial revascularization. Choice of treatment in diabetic patients is much more controversial than in non-diabetics: this because coronary artery disease is more often complex and diffuse, left ventricular function is depressed, and concomitant multiple risk factors are present. These subset of patients experience worse outcomes than non diabetic patients undergoing either coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI). Large randomized trials performed both in the early era of PCI and in the stent era suggest that CABG is superior to bare metal stent implantation in the treatment of diabetic patients with multivessel coronary artery disease. These findings are reflected in current guidelines, which favor CABG over PCI in most diabetics who require revascularization. However, substantial variability exists in practice patterns among individual hospital, suggesting a lack of clinical consensus. The major advantage of CABG over bare metal stent implantation in diabetic patients is the lower risk of repeat revascularization procedures through the follow-up. Better angiographic results have been demonstrated in the new era of drug-eluting stents (DES). Data from both the sirolimus and paclitaxel-eluting stents trials support the potential advantage of DES implantation both in diabetic and non-diabetic patients. Preliminary data from studies comparing DES versus CABG in diabetic patients with multivessel coronary artery disease suggests that 1) no significant difference exists in the 12-month rate of death, myocardial infarction and cerebrovascular events in patients treated with DES as compared to off-pump bypass surgery, 2) a difference of 7.1% in the rate of repeat revascularization at 12-month exists in favor of bypass surgery and 3) diabetic retinopathy identifies a subgroup with poor outcome after both percutaneous and surgical myocardial revascularization.

Topics: Combined Modality Therapy; Coronary Artery Disease; Diabetic Angiopathies; Drug Delivery Systems; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents; Tubulin Modulators

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

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

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

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

The history of rapamycin dates from 1965, when it was isolated from a microorganism in soil and its antibiotic properties were confirmed. Since its discovery, many scientific papers have demonstrated its antifungal and immunosuppressive properties. Our team pioneered in the study of the mechanism of action of rapamycin, motivated by its enormous promise as a therapeutic agent in atherosclerotic disease. We reported how it can inhibit the proliferation and migration of smooth muscle cells after a mechanical aggression, and demonstrated that this effect is mediated by p27 activation by rapamycin. The participation of p27, a key cyclin in the modulation of cell replication, in rapamycin's molecular signaling also spurred expectations in the field of oncological research because it involves a non-redundant system of regulation of the cell cycle susceptible to mutatio. The interesting characteristics of this active principle suggested that it would be worthwhile to investigate its protective effect in an experimental porcine model of angioplasty. Rapamycin showed that it can notably reduce vascular wall thickening, thus helping to preserve patency after angioplasty. Shortly after this study, the use of rapamycin-coated stents designed to release the active principle into the area of the atherosclerotic lesion was accompanied by an effective preservation of the arterial lumen in experimental models. It also produced a highly significant reduction in the rate of post-stent restenosis in various clinical studies in humans. However, the potential of this type of stent in diabetic patients is still unknown and we are on the point of beginning a large clinical trial (the FREEDOM study) to investigate its impact on the management of diabetic patients. Experimental and clinical evidence indicates that the development of oral agents capable of modifying the progression of atherosclerotic disease by acting on molecular targets involved in the control of the cell cycle will be a challenge in the coming years.

Topics: Animals; Atherosclerosis; Diabetic Angiopathies; Humans; Sirolimus

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

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

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

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

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

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

Ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES) proved noninferior to durable polymer everolimus-eluting stents (DP-EES) for a composite clinical end point in a population with minimal exclusion criteria. We performed a prespecified subgroup analysis of the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation (BIOSCIENCE) trial to compare the performance of BP-SES and DP-EES in patients with diabetes mellitus.. BIOSCIENCE trial was an investigator-initiated, single-blind, multicentre, randomized, noninferiority trial comparing BP-SES versus DP-EES. The primary end point, target lesion failure, was a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization within 12 months. Among a total of 2119 patients enrolled between February 2012 and May 2013, 486 (22.9%) had diabetes mellitus. Overall diabetic patients experienced a significantly higher risk of target lesion failure compared with patients without diabetes mellitus (10.1% versus 5.7%; hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.27-2.56; P=0.001). At 1 year, there were no differences between BP-SES versus DP-EES in terms of the primary end point in both diabetic (10.9% versus 9.3%; HR, 1.19; 95% CI, 0.67-2.10; P=0.56) and nondiabetic patients (5.3% versus 6.0%; HR, 0.88; 95% CI, 0.58-1.33; P=0.55). Similarly, no significant differences in the risk of definite or probable stent thrombosis were recorded according to treatment arm in both study groups (4.0% versus 3.1%; HR, 1.30; 95% CI, 0.49-3.41; P=0.60 for diabetic patients and 2.4% versus 3.4%; HR, 0.70; 95% CI, 0.39-1.25; P=0.23, in nondiabetics).. In the prespecified subgroup analysis of the BIOSCIENCE trial, clinical outcomes among diabetic patients treated with BP-SES or DP-EES were comparable at 1 year.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Coronary Angiography; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Polymers; Sirolimus; Treatment Outcome

The long-term performance of polymer-free stent systems in patients with diabetes mellitus has not been investigated extensively. This study reports long-term results of the LIPSIA Yukon trial which compared the polymer-free sirolimus-eluting Yukon Choice stent with the polymer-based paclitaxel-eluting Taxus Liberté stent in this subpopulation. At 9 months, the Yukon Choice stent failed to show non-inferiority in terms of the primary end point late lumen loss, while no significant difference in clinical outcome was detected.. The LIPSIA Yukon trial randomized 240 patients with diabetes mellitus to a polymer-free sirolimus eluting stent (Yukon Choice, Translumina) versus a polymer-based paclitaxel-eluting stent (Taxus Liberté, Boston Scientific). Clinical follow-up was conducted with a standardized telephone follow-up and all events were centrally adjudicated. Follow-up was available for 98.3% of patients after a median of 5.0 years. The incidence of all-cause death (16.9% versus 14.0%, P = 0.67), respectively definite or presumed cardiovascular death (7.6% versus 8.8%, P = 0.94) were similar in the Yukon Choice and the Taxus Liberté group. There were no significant differences in the rates of myocardial infarction (9.3% versus 7.9%, P = 0.88), definite stent thrombosis (0.8% versus 0.9%, P = 1.0), target lesion revascularization (15.3% versus 15.8%, P = 1.0), target vessel revascularization (18.6% versus 23.7%, P = 0.44), non-target vessel revascularization (18.6% versus 26.3%, P = 0.21), and stroke (3.4% versus 4.4%, P = 0.96) between patients assigned to the Yukon Choice and the Taxus Liberté stent.. At 5 years of follow-up, clinical outcome was similar between the polymer-free sirolimus-eluting Yukon Choice stent and the polymer-based paclitaxel-eluting Taxus Liberté stent.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

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

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

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

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

Diabetic patients respond less favorably to revascularization and have poorer long-term outcomes. Our main aim was to evaluate the angiographic efficacy of XIENCE V (everolimus-eluting stent, or EES) in diabetic patients compared with TAXUS Liberté (paclitaxel-eluting stent, or PES).. The SPIRIT V Diabetic Study was a prospective, single-blind, randomized study that enrolled 324 diabetic (insulin and non-insulin dependent) patients at 28 sites in Europe and Asia Pacific. Randomization was 2:1 between EES (n = 218) and PES (n = 106). The primary end point was sequential noninferiority and superiority of EES for in-stent late loss at 9 months. Secondary clinical end points included stent thrombosis, death, myocardial infarction, and revascularization rates up to 1 year.. Everolimus-eluting stent was superior to PES for in-stent late loss at 9 months (0.19 mm vs 0.39 mm, respectively; P(superiority) = .0001). The composite rate of death, myocardial infarction, and target vessel revascularization was the same in the 2 groups at 1 year (16.3% vs 16.4%). No stent thromboses (Academic Research Consortium definite and probable) were seen through 1 year with EES compared with 2 of 104 (2%) with PES (P = .11).. In this prospective, randomized trial in a high-risk group of diabetic patients, implantation of EES compared with PES resulted in significantly better inhibition of intimal hyperplasia with a comparable safety outcome.

Topics: Aged; Angioplasty, Balloon, Coronary; Asia; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Europe; Evaluation Studies as Topic; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Prospective Studies; Risk Assessment; Single-Blind Method; Sirolimus; Statistics, Nonparametric; Survival Analysis; Taxus; Treatment Outcome

To expand the paucity of data on the efficacy of various drug-eluting stents in diabetic patients.. Type 2 diabetic patients treated in our institution from October 2005 to January 2007 presenting with of de novo lesions in native coronary arteries were randomly assigned to sirolimus-eluting stents (Cypher group; n=76); paclitaxel-eluting stents (Taxus group; n=75); and everolimus-eluting stents (Endeavor group; n=75). Poor metabolic control (HbA1c >7% and low-density lipoprotein cholesterol >100 mg/dL) and microvascular complications (retinopathy and/or nephropathy) were assessed. The primary end point was the 3-year composite of major adverse cardiac events (MACE), including death of any cause, myocardial infarction, and clinically driven target vessel revascularization. MACE-free survival was 86.8% in the Cypher group, 82.5% in the Taxus group, and 64.4% in the Endeavor group (P=0.006 by log-rank test). The post hoc comparisons showed no significant difference between Cypher versus Taxus groups (adjusted P=1.0) but a higher MACE rate in the Endeavor group versus both the Cypher group (adjusted P=0.012) and the Taxus group (adjusted P=0.075). Independent predictors of 3-year MACE at Cox analysis were treatment by Endeavor versus Cypher stent (2.35 [95% confidence interval, 1.07 to 5.41]; P=0.030), multivessel disease (hazard ratio, 1.78 [95% confidence interval, 1.06 to 2.66]; P=0.031), diabetic retinopathy (hazard ratio, 1.60; [95% confidence interval, 1.03 to 2.76]; P=0.038), and poor metabolic control (hazard ratio, 1.60; [95% confidence interval, 1.02 to 2.52]; P=0.048).. The present pilot study suggests that in diabetic patients, the Endeavor stent is associated with a higher 3-year MACE rate when compared with Cypher and Taxus stents.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Pilot Projects; Sirolimus

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

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

We compared the safety and efficacy of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) with the TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) among the large cohort of randomized diabetic patients enrolled in the SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) trial.. Diabetes mellitus remains a significant predictor of adverse clinical outcomes after percutaneous coronary intervention with drug-eluting stents, and the comparative outcomes of different drug-eluting stents in diabetic patients remains ill-defined.. In the SPIRIT IV trial, 3,687 patients with up to 3 de novo native coronary artery lesions were prospectively randomized 2:1 to receive EES or PES. Randomization was stratified by the presence of diabetes and lesion complexity. The primary end point was the occurrence of target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year. Clinical outcomes were evaluated in randomized diabetic (n = 1,185 [786 EES; 399 PES]) and nondiabetic patients (n = 2,498 [1,669 EES; 829 PES]).. The EES compared with PES reduced TLF in nondiabetic patients (3.1% vs. 6.7%, p < 0.0001), with significant reductions in myocardial infarction, stent thrombosis, and target lesion revascularization. In contrast, no difference in TLF (6.4% vs. 6.9%, respectively, p = 0.80) or any of its components was present among diabetic patients, regardless of insulin use. A significant interaction between the presence of diabetes and stent type on TLF (p(interaction) = 0.02) was observed.. In the SPIRIT IV randomized trial, EES compared with PES provided similar clinical outcomes in diabetic patients and superior clinical outcomes in nondiabetic patients at 1 year. (SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT00307047).

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Prospective Studies; Sirolimus; Treatment Failure

The aim of this study was to examine outcomes related to the use of the Endeavor zotarolimus-eluting stent (ZES) (Medtronic CardioVascular, Santa Rosa, California) compared with the TAXUS paclitaxel-eluting stent (PES) (Boston Scientific Corp., Natick, Massachusetts) in the 477 patients with diabetes mellitus (DM) enrolled in the randomized ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) trial.. Percutaneous coronary intervention (PCI) in diabetic patients is associated with increased rates of restenosis-related end points compared with PCI in nondiabetic patients. Although ZES has been associated with similar clinical efficacy compared with PES in the overall trial population of the ENDEAVOR IV trial, whether these results are maintained in the higher-risk restenosis subgroup of patients with DM has not been determined.. Clinical and angiographic outcomes were compared according to randomized treatment assignment to either ZES or PES.. Baseline characteristics were similar among ZES (n = 241) and PES (n = 236) diabetic patients, with slightly longer lesion lengths in PES-treated patients (12.9 mm vs. 14.0 mm, p = 0.041). Among the 86 DM patients assigned to routine angiographic follow-up (18% of the overall DM cohort), in-stent percent diameter stenosis at 8 months was greater among ZES-treated patients (32.9 vs. 21.1, p = 0.023), with a trend toward higher in-stent late loss. One-year clinical outcomes were similar among DM patients treated with either ZES or PES (target vessel failure: 8.6% vs. 10.8%, p = 0.53; target lesion revascularization: 6.9% vs. 5.8%, p = 0.70; target vessel revascularization: 8.6% vs. 9.4%, p = 0.87). There were no significant interactions between DM status and stent type with respect to the outcomes measured, and the relative efficacy/safety of ZES and PES were similar among insulin- and noninsulin-requiring subgroups.. One-year clinical outcomes were similar among DM patients treated with ZES and PES in the ENDEAVOR IV trial. These findings parallel the overall trial results, which demonstrated similar efficacy and safety of ZES and PES for single de novo coronary lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Hypoglycemic Agents; Insulin; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Prospective Studies; Prosthesis Design; Severity of Illness Index; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome; United States

Patients with diabetes have a higher risk for in-stent restenosis after coronary stent implantation. Drug-eluting stents (DES) are highly effective in reducing in-stent restenosis. Once neointimal hyperplasia is suppressed with DES, the impact of stent underexpansion becomes magnified. The aim of this study was to evaluate DES expansion in patients with diabetes. Ninety-five patients with diabetes were randomized to Cypher Select (n = 48) or Taxus Express-2 (n = 47) stent implantation. Intravascular ultrasound was performed after stent implantation. Stent expansion was defined as the ratio of measured to predicted minimum stent diameter. There was a trend for lower stent expansion in the Cypher Select stent group (0.74 +/- 0.08 vs 0.78 +/- 0.11 in the Taxus Express-2 stent group, p = 0.061). Cypher Select stents achieved a final minimal stent cross-sectional area of 5.5 +/- 1. 8 mm2, compared with 6.4 +/- 1.9 mm2 for Taxus Express-2 stents (p = 0.015). For stents with nominal diameters > or =2.75 mm (Cypher Select n = 40, Taxus Express-2 n = 38), 42.5% of the Cypher Select stents and 10.5% of the Taxus Express-2 stents did not achieve a final minimum stent area of 5 mm2 (p = 0.002). Insulin treatment (relative risk 0.31, 95% confidence interval 0.10 to 0.95, p = 0.041) and stent type (relative risk 0.15, 95% CI 0.04 to 0.53, p = 0.003) were independent predictors of not achieving a minimum stent area >5.0 mm2. In conclusion, an important percentage of DES in patients with diabetes fail to achieve the manufacturers' predicted final minimal stent diameter. Cypher Select stent and insulin treatment were independent predictors of not achieving a minimum stent area >5.0 mm2.

Topics: Aged; Coronary Restenosis; Diabetes Mellitus; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Risk Factors; Sirolimus; Ultrasonography, Interventional

Diabetes has been reported as an independent predictor of restenosis after drug-eluting stent implantation. The purpose of this study was to assess the long-term impact of increased drug dose in sirolimus-eluting stents (SES) on neointimal hyperplasia (NIH) in diabetic patients using volumetric intravascular ultrasound analysis.. The 3D trial is a multicenter, prospective, randomized, feasibility study of double-dose (280 microg/cm2) or conventional single-dose (140 microg/cm2) SES for the treatment of de novo coronary lesions in diabetic patients. To evaluate long-term efficacy, complete serial volumetric analyses (baseline, 6-month and 2-year follow up) were performed in 39 diabetic patients (17 single-dose, 22 double-dose). Each volume was divided by stent length to acquire volume index, expressed as mm3/mm. Percent neointimal volume was calculated as (neointimal volume/stent volume) x 100 at follow up.. Volumetric analysis showed similar results over time between the 2 stent groups (p = NS for all). At 2-year follow up, minimal increases in NIH area and percent NIH were observed in both groups, which translated into a decrease in lumen volume index compared to baseline (p < 0.05 for all). No late-acquired incomplete stent apposition was observed in either group.. The current single dose of sirolimus in SES is effective in inhibiting NIH in diabetic patients up to 2 years. In this patient subset, double-dose SES did not confer additional NIH suppression at 2-year follow up compared to conventional single-dose SES.

Topics: Blood Vessel Prosthesis Implantation; Coronary Restenosis; Diabetic Angiopathies; Dose-Response Relationship, Drug; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Sirolimus; Tunica Intima; Ultrasonography, Interventional

Patients with diabetes have increased risk of in-stent restenosis after coronary stent implantation owing to neointimal hyperplasia (NIH). The aim of the study was to evaluate the extent and distribution of NIH with intravascular ultrasound (IVUS) after coronary artery stenting with sirolimus-eluting (Cypher) or paclitaxel-eluting (Taxus) stents in diabetic patients.. One hundred and thirty diabetic patients were randomized to Cypher or Taxus stent implantation. IVUS was performed at 8 month follow-up. NIH volume was significantly reduced in the Cypher group when compared with the Taxus group: median (inter-quartile range) 0.0 (0.0-0.0) vs. 8.0 mm(3) (0.1-33.0), P < 0.001. Per cent NIH volume was also significantly lower in Cypher stents compared with Taxus stents: median (inter-quartile range) 0.0 (0.0-0.0) vs. 7.5% (0.1-27.0), P < 0.001. NIH was covering 5.4% of the stent length in the Cypher stents compared with 46.1% in the Taxus stents (P < 0.001). The incidence of diffuse NIH was significantly higher for Taxus than for Cypher stents (42.9 vs. 3.5%, P < 0.001). Taxus stents had more often NIH at the proximal stent edge compared with Cypher stents (45.1 vs. 7%, P < 0.001) and no Cypher stents had NIH at the distal stent edge compared with 35.5% of the Taxus stents (P < 0.001).. In diabetic patients, the Cypher stent, compared with the Taxus stent, inhibited NIH more effectively and had a more focal NIH pattern including less involvement of the stent edges.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Sirolimus; Treatment Outcome; Tunica Intima; Ultrasonography

We evaluated the pharmacokinetics of the eluted everolimus by assessing systemic drug release and distribution of everolimus-eluting stents.. Drugs eluted by a coronary stent might cause adverse events such as tumors, infections, or noncardiac death. The systemic exposure of the drugs is unknown because there are only limited data about pharmacokinetics of drug-eluting stents in humans.. Venous blood samples in a subset of 39 patients were drawn just before implantation of the first stent (baseline, 0-minute time point) and at 10 and 30 minutes and 1, 2, 4, 6, 12, 24, 36, 48, 72, 168, and 720 hours (30 days) after completion of implantation of the last stent. Whole blood concentrations of everolimus were determined using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method.. The total dose of everolimus received by the patients ranged from 53 to 588 microg. The last time point up to which whole blood concentrations could be quantified ranged per patient from 4 to 720 hours after implantation of the last stent. Across all dose levels, individual T(max) values ranged from 0.13 and 2.17 hours; individual C(max) ranged from 0.14 to 2.79 ng/mL.. This study confirms the limited exposure to the systemic circulation of the eluted drug with the use of the XIENCE V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, CA). Therefore, a systemic cause of adverse events is unlikely.

Topics: Aged; Angioplasty, Balloon, Coronary; Area Under Curve; Chromatography, High Pressure Liquid; Coronary Disease; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Half-Life; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus

It is still controversial whether sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) are equally effective in patients with diabetes. In these patients, multiple individual variables may be responsible for neointimal hyperplasia, thus making difficult the comparison of the two drug-eluting stents (DES).. We designed a prospective, randomized study to compare the efficacy in prevention of restenosis of SES and PES, both implanted in the same diabetic patient with multiple de novo coronary artery lesions undergoing elective percutaneous coronary intervention. We enrolled 60 patients with diabetes with at least two significant de novo angiographic stenoses in different coronary segments. The primary end point was in-stent late luminal loss (LLL) at 8-month angiographic follow-up.. A total of 120 lesions were successfully treated with the randomly assigned DES (SES, n = 60; PES, n = 60). In-stent LLL was lower in the SES than in the PES group (0.26 +/- 0.4 vs. 0.50 +/- 0.6 mm; P = 0.01). Coronary lesions treated with SES presented a reduced in-stent LLL in 40 (68%) patients, while PES resulted in a lower in-stent LLL in 19 (32%) patients (P = 0.0002). At multivariable analysis, the type of DES implanted was the only independent predictor of in-stent LLL (odds ratio 2.3 [95% CI 1.1-5.0]; P = 0.03).. SES directly compared with PES in the same diabetic patient is associated with a decrease in the extent of in-stent LLL at 8 months, suggesting a reduced risk of restenosis.

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Agents; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Paclitaxel; Prospective Studies; Sirolimus

Wall shear stress (WSS) has been associated with neointimal hyperplasia (NIH) following bare metal stent (BMS) implantation. Drug-eluting stents (DES) almost abolish NIH. Conversely, diabetes mellitus amplifies NIH response. The association between WSS and arterial wall response following DES and BMS implantation in diabetic patients remains to be evaluated.. The study involved 20 diabetic patients randomized to BMS (n = 9) or sirolimus-eluting stent (SES; n = 11) implantation in native coronary arteries. A computational fluid dynamic model applied 3D intravascular ultrasound (IVUS) and two-plane angiographic to measure WSS (Pa). IVUS assessments were performed post-procedure and at 9-months follow-up. The target segment encompassed the stent plus 5 mm distal and proximal edges. A total of 93 subsegments were evaluated: in-stent segments divided in three subsegments (proximal, mid and distal; n = 60) and proximal and distal edges (n = 33).. Stent length was similar between BMS (17.4 +/- 7.3 mm) and SES (19.8 +/- 6.8 mm) groups. NIH was observed in all BMS subsegments (n = 27) versus one subsegment in the SES group (n = 33). WSS ranged from 0.52 to 4.20 Pa in the BMS and from 0.42 to 3.06 Pa in the SES group. There was no correlation between WSS and NIH in either stent group. In addition, there were no correlation between the change of external elastic membrane (EEM) or plaque growth at the edges and WSS.. WSS was not associated with NIH after implantation of SES or BMS in diabetic patients. Plaque growth or the change of EEM at the edges were not associated with WSS either.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Computer Simulation; Coronary Angiography; Coronary Circulation; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Female; Hemorheology; Humans; Hyperplasia; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Metals; Middle Aged; Models, Cardiovascular; Pulsatile Flow; Sirolimus; Stents; Stress, Mechanical; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents.. In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE (defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% (14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% (7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years.. Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patients.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Male; Myocardial Revascularization; Paclitaxel; Sirolimus; Treatment Outcome; Tubulin Modulators

With the introduction of drug-eluting stents (DES), the angiographic rates of restenosis have reduced dramatically but less prominently in diabetic patients. We compared the effects of sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES) on 6-month angiographic and clinical outcomes in Korean diabetic patients.. Diabetic patients with de novo coronary lesions (169 patients with 190 lesions) were randomly assigned to either SES or PES in six different cardiovascular centers from April 2005 to January 2006. Patients with vessel size >2.0 mm and < or =2 vessel diseases requiring < or =2 DES implantation were included in the study.. Baseline clinical and angiographic characteristics were similar between the two groups. At 6-month follow-up, the late lumen loss (0.26 +/- 0.76 in the SES group vs. 0.39 +/- 0.92 mm in the PES group, P = 0.356) and the rate of binary restenosis (2.8%[n = 2] in the SES group vs. 6.9%[n = 5] in the PES group, P = 0.441) showed no significant differences. Rates of death (1.2%[n = 1] in the SES group vs. 1.2%[n = 1] in the PES group, P = 1.000), myocardial infarction (1.2%[n = 1] in the SES group vs. 1.2%[n = 1] in the PES group, P = 1.000), and target lesion revascularization (2.4%[n = 2] in the SES group vs. 4.8%[n = 4] in the PES group, P = 0.443) were similar in both groups during 6 months of follow-up.. The use of either SES or PES demonstrated similar 6-month angiographic and clinical outcomes in Korean diabetic patients with coronary artery disease.

Topics: Aged; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Stenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Korea; Male; Middle Aged; Paclitaxel; Prospective Studies; Secondary Prevention; Sirolimus; Treatment Outcome

Sirolimus stent implantation has been demonstrated to be safe and effective in diabetics; however, the long-term outcomes in this high-risk population remain unknown. The aim of this study was to determine the long-term safety and efficacy of the sirolimus-eluting stent (SES) when compared with the bare metal stent (BMS) in patients included in the DIABETES (DIABETes and sirolimus Eluting Stent) trial.. The prospective multicentre DIABETES trial randomized 160 diabetic patients with one or more significant coronary stenoses in one, two, or three vessels to either SES or BMS implantation. One-year dual antiplatelet therapy (aspirin plus clopidogrel) was routinely prescribed. Clinical follow-up was scheduled at 1, 9, 12, and 13 months and 2 years. Baseline clinical and angiographic characteristics were comparable between groups. At 2 years, the rate of target lesion revascularization was significantly lower in the SES group compared with the BMS group (7.7 vs. 35.0%, P < 0.001). However, the total revascularization rate at 2 years increased in both groups due to progression of atherosclerosis in coronary segments remote from the target lesion (rate of atherosclerosis progression: 7.7% in SES group vs. 10% in BMS group; P = 0.7). During dual antiplatelet treatment (1 year), there was no stent thrombosis in the SES group, whereas two patients presented it in the BMS group. However, after clopidogrel withdrawal, three patients allocated to the SES group presented stent thromboses vs. none in the BMS group.. SES implantation in diabetic patients remains effective at 2-year follow-up. However, clinical efficacy appeared to be reduced by the occurrence of stent thrombosis between 1 and 2 years.

Topics: Aged; Aspirin; Blood Vessel Prosthesis; Clopidogrel; Coronary Restenosis; Coronary Stenosis; Death, Sudden, Cardiac; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Failure; Reoperation; Sirolimus; Ticlopidine; Treatment Outcome

A predefined intravascular ultrasound (IVUS) substudy was performed to evaluate the vascular effects of sirolimus-eluting stent (SES) versus bare-metal stent (BMS).. The Diabetes and Sirolimus-Eluting Stent (DIABETES) trial is a prospective, multicenter, randomized, controlled trial aimed at demonstrating the efficacy of the SES compared with BMS in diabetic patients.. Serial intravascular ultrasound analyses were performed in 140 lesions (SES = 75; BMS = 65) immediately after stent implantation and at nine-month follow-up. Vessel, luminal, and stent mean areas and volumes were evaluated at both edges and within the stented segment. Qualitative assessment of residual dissections and stent apposition were also performed.. Baseline clinical and angiographic characteristics were similar between groups. At 9 months, in-stent neointimal hyperplasia (NIH) mean area and volume were significantly reduced in the SES group (median NIH area 0.01 mm2 [0.0 to 0.1] vs. 2.0 mm2 [1.0 to 2.9] and median NIH volume 0.11 mm3 [0 to 2.1] vs. 35.3 mm3 [16.6 to 62.6]; both p < 0.0001). In the SES group, stent edges evidenced significant increase in lumen dimensions mainly due to significant increase in vessel volume, whereas those of the BMS group presented vessel shrinkage leading to significant lumen reduction. Late acquired incomplete stent apposition was observed in 11 lesions (14.7%) in the SES group and 0 in the BMS group (p = 0.001). At one year, no stent thromboses occurred in malapposed stents.. The SES implantation effectively inhibits NIH in diabetic patients. The antirestenotic effect of SES is also appreciated at the stent edges. Late acquired stent malapposition is a frequent phenomenon in diabetic patients treated with SES.

Topics: Aged; Coronary Angiography; Coronary Disease; Diabetic Angiopathies; Equipment Design; Female; Follow-Up Studies; Humans; Hyperplasia; Imaging, Three-Dimensional; Male; Metals; Middle Aged; Sirolimus; Stents; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional

This study sought to evaluate the effectiveness and safety of the sirolimus-eluting stent in the treatment of in-stent restenosis (ISR) in consecutive unselected patients undergoing coronary intervention in a real-world scenario.. Restenosis after bare metal stenting is characterized by a high rate of re-restenosis once treated with repeated percutaneous coronary intervention.. The study was designed as a prospective two-center registry. We enrolled 244 patients with ISR in a native coronary artery or saphenous vein graft who had clinical indication for repeat intervention.. Sirolimus stent implantation was successful in all lesions. At 9-month follow-up, death occurred in 4 (1.6%) patients, myocardial infarction in 4 (1.6%), and ischemia-driven target lesion revascularization (TLR) in 12 (4.9%), for a cumulative event-free survival of 227 (93%). Although 9-month follow-up angiography was planned in all patients, only 150 (62%) patients completed it, and restenosis was present in 13 (8.7%) patients. Diabetes and non-ST-segment elevation acute coronary syndrome at presentation were the only independent predictors of freedom from ischemia-driven TLR and major adverse cardiac events.. Sirolimus stent implantation for the treatment of ISR is effective and safe. In diabetic patients and in those with acute coronary syndrome, the higher rate of recurrence requires further evaluation.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Diabetic Angiopathies; Female; Humans; Immunosuppressive Agents; Italy; Male; Middle Aged; Prospective Studies; Registries; Sirolimus; Stents; Survival Analysis; Treatment Outcome

To analyse the impact of sirolimus-eluting stents (SES) on long-term outcomes in patients with coronary artery disease (CAD) and diabetes.. Among 1004 patients with CAD undergone percutaneous coronary intervention (PCI), 84 diabetic and 250 non-diabetic patients received SES, 168 diabetic and 502 non-diabetic patients had bare metal stent (BMS) implantation. Baseline clinical characteristics, interventional procedures (coronary angiography and PCI), occurrence of major adverse cardiac events (MACE), and MACE-free survival rates at one year during follow-up were compared.. During follow-up (average 16.2 months), patients (with and without diabetes mellitus) who received SES had similar occurrence of MACE (4.8% vs. 3.6%, P = 0.744) and MACE-free survival rates at one year (95.0% vs. 96.7%, P = 0.602). However those received BMS had a higher occurrence of MACE in diabetes mellitus than that in non-diabetic patients (31.0% vs. 21.7%, P = 0.015). MACE-free survival rate at one year was lower in diabetic patients with BMS than that in non-diabetic patients with BMS (74.2% vs. 86.8%, P = 0.001).. Implantation of sirolimus-eluting stents may reduce the major adverse cardiac events and the frequency of repeat intervention in patients with diabetes mellitus.

Topics: Coronary Disease; Diabetic Angiopathies; Female; Humans; Male; Retrospective Studies; Sirolimus; Stents

To investigate the relationship between coronary artery remodelling and glycaemic and lipid profiles in diabetic patients.. Intravascular ultrasound analyses of 131 angiographically non-significant coronary stenoses in 80 diabetic patients were performed. The remodelling index (RI) was calculated as the ratio between total vessel area at target site and total vessel area at proximal reference, and was assessed in two ways: as a continuous variable, and as a binary categorical variable: RI<1 namely, negative remodelling (group I), or RI> or =1 (group II). Percentage cross-sectional narrowing was 57+/-13%. On average, RI was 0.93+/-0.13. Coronary shrinkage was found in 94 (71.7%) lesions. Significant inverse correlations were demonstrated between RI and total cholesterol (r=-0.26, P=0.003), apolipoprotein-B (r=-0.23, P=0.01) and LDL-cholesterol (r=-0.3, P=0.001) levels. Multivariable lineal regression analysis identified LDL-cholesterol as the only independent predictor of RI (P=0.001).. Negative remodelling is a frequent finding in diabetics and it is associated with LDL-cholesterol levels. This may contribute to the diffuse coronary artery disease observed in diabetic patients.

Topics: Aged; Blood Glucose; Cholesterol, LDL; Coronary Stenosis; Coronary Vessels; Diabetic Angiopathies; Female; Humans; Immunosuppressive Agents; Insulin Resistance; Male; Prospective Studies; Sirolimus; Stents; Ultrasonography

Outcomes after percutaneous coronary interventions in diabetic patients are shadowed by the increased rate of recurrence compared with nondiabetic patients.. We conducted a multicenter, randomized trial to demonstrate the efficacy of sirolimus-eluting stents compared with standard stents to prevent restenosis in diabetic patients with de novo lesions in native coronary arteries. The primary end point of the trial was in-segment late lumen loss as assessed by quantitative coronary angiography at 9-month follow-up. The trial was stratified by diabetes treatment status. One hundred sixty patients were randomized to sirolimus-eluting stents (80 patients; 111 lesions) or standard stent implantation (80 patients; 110 lesions). On average, reference diameter was 2.34+/-0.6 mm, lesion length was 15.0+/-8 mm, and 13.1% of lesions were chronic total occlusions. In-segment late lumen loss was reduced from 0.47+/-0.5 mm for standard stents to 0.06+/-0.4 mm for sirolimus stents (P<0.001). Target-lesion revascularization and major adverse cardiac event rates were significantly lower in the sirolimus group (31.3% versus 7.3% and 36.3% versus 11.3%, respectively; both P<0.001). Non-insulin- and insulin-requiring patients demonstrated similar reductions in angiographic and clinical parameters of restenosis after sirolimus-eluting stent implantation. During the 9-month follow-up, stent thrombosis occurred in 2 patients after standard stent implantation. Conversely, this phenomenon was not seen in the sirolimus stent group.. This randomized trial demonstrated that sirolimus stent implantation is safe and efficacious in reducing both angiographic and clinical parameters of restenosis compared with standard stents in diabetic patients with de novo coronary stenoses.

Topics: Aged; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Coronary Restenosis; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Equipment Design; Female; Humans; Male; Middle Aged; Sirolimus; Stents

Patients with diabetes mellitus have less favourable outcomes after percutaneous coronary intervention (PCI) than non-diabetics. We performed a subgroup analysis of the multicentre RAVEL trial to examine the impact of the sirolimus-eluting stent (SES) on outcomes in diabetic patients. The RAVEL study randomized 238 patients to treatment with either sirolimus-eluting or bare metal stents. Forty-four patients were diabetic; 19 received sirolimus-eluting stents and 25 were treated with bare metal stents. The differences in outcomes between diabetic and non-diabetic patients treated with SES (n=101) were also assessed. Follow-up angiography was performed at 6 months. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), or target lesion revascularization (TLR) were analysed at 12-month follow-up. Six-month in-stent late lumen loss was significantly lower for the diabetic SES than the bare stent group (0.07+/-0.2 vs 0.82+/-0.5mm; P<0.001) and similar to that in non-diabetics treated with SES (-0.03+/-0.27mm). There was zero restenosis in the SES groups (diabetic and non-diabetic) compared to a 42% rate in the diabetic population assigned to bare metal stents (P=0.001). After 12 months, there was one non-Q-wave MI and one non-cardiac death in the diabetic SES group, while 12 patients in the bare metal stent group had MACE (one death, two MI, nine TLR) (P=0.01)-an event-free survival rate of 90% vs 52%, respectively (P<0.01). There were no TLRs in both SES groups compared to 36% rate in the diabetic bare metal stent group (P=0.007). Conclusion Diabetics treated with SES were associated with a virtual abolition of neointimal proliferation and low event rates at long-term follow-up.

Topics: Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Stents; Tunica Intima

Diabetes mellitus (DM) plays an important role in restenosis and late in-stent thrombosis (ST). The current study using optical coherence tomography (OCT) aims to compare target lesion neointima in patients with or without diabetes after zotarolimus-eluting stent (ZES) treatment.. OCT images of 90,212 struts and quantitative coronary angiography (QCA) in 62 patients (32 with DM and 30 without DM) with 69 de novo coronary lesions (34 DM and 35 non-DM) both after ZES implantation and 12 ± 1 month angiographic follow-up were recorded. Patient characteristics, lesion characteristics, clinical outcomes, and OCT findings including neointimal thickness, coverage, malapposition, and intimal morphology were analyzed.. Baseline patient characteristics and lesion characteristics data were similar between the two groups. Higher neointimal thickness (0.14 ± 0.09 mm vs. 0.09 ± 0.04 mm, p = 0.021), more neovascularization (3.03 ± 6.24 vs. 0.52 ± 1.87, p = 0.017) and higher incidence of layered signal pattern (12.19 ± 19.91% vs. 4.28 ± 9.02%, p = 0.049) were observed in diabetic lesions comparing with non-diabetic lesions. No differences were found in malapposition, uncovered percentage, and thrombus between the two groups (all p > 0.05). Occurrence of clinical adverse events was also similar during the follow-up period (p > 0.05).. Although more neointimal proliferation and more neovascularization were found in diabetic coronary lesions when compared with non-diabetic lesions, treatment with ZES showed similar stent malapposition rate at 1-year follow-up. The data indicated that ZES treatment could possibly be effective in treating diabetic coronary lesions.. ClinicalTrials.gov identifier, NCT01747356.

Topics: Aged; Case-Control Studies; Coronary Angiography; Coronary Vessels; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

We conducted propensity-score-matched comparisons of midterm angiographic follow-up outcomes of sirolimus- versus everolimus-eluting stents (SES, EES) after elective placements for de novo coronary stenosis in small vessels (SV) in patients with diabetes mellitus (DM), because the angiographic efficacy of EES over SES for those cohorts remained unclear. The study was a non-randomized, retrospective, lesion-based, multicenter study, examining lesions followed up angiographically within 550 days, extracted from the unified database of 6 institutes. The endpoint (binary restenosis) was defined as the percentage of subjects having >50% diameter stenosis at follow-up. Propensity-score-matched analyses were conducted in 3 different vessel-size cohorts, defined by a preprocedural reference diameter (RD) <2.10, <2.35, and <2.60 mm, yielding group sizes of n = 107, 183, and 312 baseline-adjusted lesions in each of the 2 stent arms. The frequency of binary restenosis decreased significantly with increasing vessel size, at 16.8, 12.6, and 12.2%, in the SES group. However, it remained almost the same across vessel-size groups in the EES group (8.0, 6.0, and 7.5%). The p values for the significance of the differences in binary restenosis between EES and SES in each vessel size increased with the decrease in vessel size [p = 0.002, 0.040, and 0.063 (the last still nearly significant)]. Thus, in patients with DM, EES showed increasingly superior efficacy over SES for SV stenosis as the vessel size became smaller, i.e., the risk for binary restenosis became greater.

Topics: Aged; Coronary Angiography; Coronary Stenosis; Coronary Vessels; Diabetes Mellitus; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Percutaneous Coronary Intervention; Propensity Score; Retrospective Studies; Sirolimus; Treatment Outcome

Diabetes is associated with aggressive atherosclerosis, leading to an increased risk of in-stent restenosis and stent thrombosis. Bioresorbable scaffolds (BRS) are a new technology for the treatment of coronary lesions that might be beneficial due to their dissolving character, especially in diabetic patients.. This study was designed to evaluate feasibility and mid-term clinical outcome of the implantation of PLLA-based, everolimus-eluting BRS for the treatment of coronary lesions in a diabetic all-comers population.. All patients of an all-comers registry with diabetes eligible for BRS implantation were included. Outcome parameters were target vessel failure (TVF), major adverse cardiac events (MACE) including target lesion revascularization (TLR), cardiac death, and myocardial infarction. Follow-up was conducted via telephone and/or office visit.. A total of 120 diabetic patients were included. Of all diabetics, 35.0% had insulin-dependent diabetes, and all other patients were treated with oral antidiabetics or dietary modification. The median age was 67 (59-72) years and 26.7% were female. Patients underwent coronary angiography due to acute coronary syndrome in 50.8%. Of 127 lesions, 60.6% were B2/C lesions according to ACC/AHA classification. The 6-month rates of TVF, TLR, and MACE were 8.9, 2.7, and 8.4%, respectively.. This evaluation confirms reasonable clinical outcome of bioresorbable vascular scaffold implantation in a high-risk diabetic population with predominately complex lesions during daily clinical practice. Nevertheless, long-term data are required for final evaluation.

Topics: Absorbable Implants; Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Stenosis; Diabetic Angiopathies; Drug-Eluting Stents; Feasibility Studies; Female; Follow-Up Studies; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Registries; Risk Assessment; Severity of Illness Index; Sirolimus; Survival Rate; Treatment Outcome

Topics: Cardiovascular Agents; Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Male; Paclitaxel; Percutaneous Coronary Intervention; Polymers; Sirolimus

This study sought to compare everolimus-eluting stents (EES) versus Resolute zotarolimus-eluting stents (ZES) in terms of patient- or stent-related clinical outcomes in an "all-comer" group of patients with diabetes mellitus (DM) who underwent percutaneous coronary intervention.. DM significantly increases the risk of adverse events after percutaneous coronary intervention. The efficacy and safety of second-generation drug-eluting stents, in particular EES versus ZES, in patients with DM have not been extensively evaluated.. Patients with DM (1,855 of 5,054 patients, 36.7%) from 2 prospective registries (the EXCELLENT [Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting] registry and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]) who were treated with EES (n = 1,149) or ZES (n = 706) were compared. Stent-related outcome was target lesion failure (TLF), and patient-oriented composite events were a composite of all-cause mortality, any myocardial infarction, and any revascularization.. Despite a higher risk patient profile in the ZES group, both TLF (43 of 1,149 [3.7%] vs. 25 of 706 [3.5%], p = 0.899) and patient-oriented composite events (104 of 1,149 [9.1%] vs. 72 of 706 [10.2%], p = 0.416) were similar between the EES and ZES in patients with DM at 1 year. In those without DM, EES and ZES also showed comparable incidence of TLF (39 of 1,882 [2.1%] vs. 33 of 1,292 [2.6%], p = 0.370) and patient-oriented composite events (119 of 1,882 [6.3%] vs. 81 of 1,292 [6.3%], p = 0.951), which were all significantly lower than in the DM patients. These results were corroborated by similar findings from the propensity score-matched cohort. Upon multivariate analysis, chronic renal failure was the most powerful predictor of TLF in DM patients (hazard ratio: 4.39, 95% confidence interval: 1.91 to 10.09, p < 0.001).. After unrestricted use of second-generation drug-eluting stents in all-comers receiving percutaneous coronary intervention, both EES and ZES showed comparable clinical outcomes in the patients with DM up to 1 year of follow-up. DM compared with non-DM patients showed significantly worse patient- and stent-related outcomes. Nonetheless, overall incidences of TLF were low, even in the patients with DM, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents in this high-risk subgroup of patients.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Patient Selection; Percutaneous Coronary Intervention; Propensity Score; Proportional Hazards Models; Prosthesis Design; Registries; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Artery Disease; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Percutaneous Coronary Intervention; Sirolimus

We sought to perform a propensity score-matched lesion-based comparison of mid-term angiographic outcomes of sirolimus- (SES, Cypher Bx Velocity) and paclitaxel- (PES, TAXUS Liberté, the 2nd-generation TAXUS) eluting stents to treat de novo coronary stenosis and, particularly, in patients with diabetes mellitus (DM) in a daily practice environment.. The present study was a non-randomized, retrospective, lesion-based, single center study that included 1,287 de novo native coronary stenosis cases after successful SES or PES placement between February 2007 and April 2011. The primary endpoint was angiographic-based binary in-stent restenosis (% diameter stenosis >50 at secondary angiogram) within 550 days of placement. A propensity score-matched analysis was used to adjust the baselines.. Among 360 baseline-adjusted angiographic lesions followed up in each arm, the incidence of the primary endpoint in the PES group (11.7%, follow-up period: 350±76 days) was not significantly different from that in the SES group (10.3%, p=0.645, 354±81 days, p=0.912). PES was not associated with the primary endpoint by logistic regression analysis (odds ratio: 1.15, 95% confidence interval: 0.68-1.93, p=0.605). In the DM specific sub-analysis, the primary endpoint in the PES group (19.6%) was not significantly different from that in the SES group (12.8%, p=0.105) in 148 baseline-adjusted lesions in each arm.. The mid-term angiographic outcomes after TAXUS Liberté placement for all-comer de novo native coronary stenosis and in patients with DM were not significantly different from those of SES in a Japanese daily practice environment.

Topics: Aged; Antineoplastic Agents; Coronary Angiography; Coronary Stenosis; Diabetes Complications; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Odds Ratio; Paclitaxel; Percutaneous Coronary Intervention; Propensity Score; Retrospective Studies; Sirolimus; Treatment Outcome

Topics: Cardiovascular Agents; Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus

This study aimed to analyze the use of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in an unrestricted diabetic population and to compare the performance of these two drug-eluting stents.. EES have demonstrated superiority in efficacy when compared to PES in a general population. However, it is controversial whether this superiority holds true in a diabetic population.. From March 2004 to May 2010, 968 patients with consecutive diabetes who underwent percutaneous coronary intervention and implantation of an EES (n = 388) or PES (n = 580) at our institution. In-hospital, 1-month, 6-month, and 1-year clinical outcomes were analyzed and compared. Correlates of major adverse cardiac events (MACE) were identified.. Baseline clinical characteristics were similar between stent types except for more family history of coronary artery disease in the PES group and more insulin-dependent diabetes and unstable angina at initial diagnosis in the EES group. The PES group had higher number of lesions treated, longer stents used, and a higher proportion of intravascular ultrasound and glycoprotein IIb/IIIa inhibitor use. The EES group had more type C and distal lesions. There was higher target lesion revascularization (TLR)-MACE in the PES group (3.3% vs. 1.0%, P = 0.03) as well as a higher rate of stent thrombosis (ST) (8 patients vs. 0 in the EES group, P = 0.03). ST continued to be higher in the PES group at 6 and 12 months and mortality was higher at 12 months in the PES group (9.4% vs. 5.2%, P = 0.02). After adjustment, no significant differences were found between stent types on Cox regression analysis for hazard ratios at 1-year follow-up of TLR-MACE.. In a diabetic population undergoing PCI, the use of an EES compared to PES was associated with lower rates of stent thrombosis; but after adjustment the composite TLR-MACE at 1 year was similar between both stents.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Diabetic Angiopathies; Disease-Free Survival; District of Columbia; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Proportional Hazards Models; Prosthesis Design; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes.. Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M-10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours.. After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥ 10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect.. After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients.

Topics: Animals; Apoptosis; Cardiovascular Agents; Cells, Cultured; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Endothelial Cells; Everolimus; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Necrosis; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Time Factors; Wound Healing

This study sought to study the second-generation everolimus-eluting stent (EES) as compared with first-generation sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) in diabetes mellitus (DM) patients.. There are limited data available comparing clinical outcomes in this setting with EES and SES, whereas studies comparing EES with PES are not powered for low-frequency endpoints.. All DM patients treated with EES, PES, or SES from January 18, 2007, to July 29, 2011, from the SCAAR (Swedish Coronary Angiography and Angioplasty Registery) were included. The EES was compared with SES or PES for the primary composite endpoint of clinically driven detected restenosis, definite stent thrombosis (ST), and all-cause mortality.. In 4,751 percutaneous coronary intervention-treated DM patients, 8,134 stents were implanted (EES = 3,928, PES = 2,836, SES = 1,370). The EES was associated with significantly lower event rates compared with SES (SES vs. EES hazard ratio [HR]: 1.99; 95% confidence interval (CI): 1.19 to 3.08). The same was observed when compared with PES (PES vs. EES HR: 1.33; 95% CI: 0.93 to 1.91) but did not reach statistical significance. These results were mainly driven by lower incidence of ST (SES vs. EES HR: 2.87; 95% CI: 1.08 to 7.61; PES vs. EES HR: 1.74, 95% CI: 0.82 to 3.71) and mortality (SES vs. EES HR: 2.02; 95% CI: 1.03 to 3.98; PES vs. EES HR: 1.69; 95% CI: 1.06 to 2.72). No significant differences in restenosis rates were observed between EES and SES or PES (SES vs. EES HR: 1.26; 95% CI: 0.77 to 2.08; PES vs. EES HR: 1.05; 95% CI: 0.71 to 1.55).. In all-comer DM patients the use of EES was associated with improved outcomes compared with SES and PES mainly driven by lower rates of ST and mortality. These results suggest better safety rather than efficacy with EES when compared with SES or PES.

Topics: Aged; Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Registries; Retrospective Studies; Sirolimus; Sweden

Topics: Angioplasty, Balloon, Coronary; Coronary Artery Disease; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Humans; Paclitaxel; Sirolimus

Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry.. Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed.. PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.

Topics: Aged; Angioplasty, Balloon, Coronary; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; National Heart, Lung, and Blood Institute (U.S.); Paclitaxel; Prospective Studies; Registries; Sirolimus; United States

Since the introduction of drug-eluting stents, the optimum revascularization strategy in diabetic patients with multivessel coronary disease has remained controversial.. This study used multivariate logistic regression analysis and propensity score matching to compare results in 270 consecutive diabetic patients (2000-2004) with multivessel disease (> or =2 vessels with a >70% de novo stenosis involving the proximal left anterior descending coronary artery) who underwent either coronary artery bypass grafting (CABG; n=142) or implantation of a drug-eluting stent (DES; i.e. rapamycin or paclitaxel; n=128). The following clinical outcomes (i.e. major adverse cardiac or cerebrovascular events [MACCEs]) were assessed: death, nonfatal myocardial infarction (MI), stroke and repeat revascularization at 2 years.. Patients who received DESs were older (67.5+/-7 years vs. 65.3+/-8 years; P=.05) and more often had a previous MI (49.2% vs. 28.2%; P< .01), but no more often had a depressed left ventricular ejection fraction < or =45% (32.4% vs. 28.1%). Coronary anatomy was more complex in surgical patients (SYNTAX score, 25.9+/-7 vs. 18.5+/-6; P< .001) and the quality of revascularization was better (i.e. anatomically complete revascularization: 52.8% vs. 28.1%; P< .01). The incidence of MACCEs was 18.7% in the CABG group and 21.8% in the DES group (adjusted odds ratio [OR] = 0.93; 95% confidence interval [CI], 0.47-1.86). The composite endpoint of death, MI or stroke occurred in 15.8% undergoing CABG and 12.9% receiving a DES (adjusted OR = 1.19; 95% CI, 0.72-1.88). There was less need for revascularization in CABG patients (4.3% vs. 12.1%; adjusted OR = 0.42; 95% CI, 0.16-1.14; P=.09).. In an unselected population of diabetic patients with multivessel coronary disease, the principle advantage of CABG was the reduced need for revascularization. There was no difference in the rate of death, MI or stroke.

Topics: Aged; Antineoplastic Agents, Phytogenic; Cohort Studies; Coronary Artery Bypass; Coronary Disease; Diabetic Angiopathies; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Logistic Models; Male; Middle Aged; Myocardial Revascularization; Paclitaxel; Retrospective Studies; Sirolimus; Treatment Outcome

Drug-eluting stents are more effective in reducing restenosis than bare-metal stents. Less certain is the relative performance of 2 widely used drug-eluting stents-sirolimus- and paclitaxel-eluting stents-in diabetic and nondiabetic patients undergoing percutaneous coronary intervention in routine clinical practice. We therefore studied the long-term effectiveness and safety of sirolimus versus paclitaxel stents overall and stratified by the absence or presence of diabetes.. We compared sirolimus and paclitaxel stents in a propensity-score matched cohort of 2054 pairs of patients (835 matched pairs of diabetic patients and 1219 matched pairs of nondiabetic patients) undergoing percutaneous coronary intervention in Ontario between December 1, 2003 and March 31, 2006. The cohort was derived from the Cardiac Care Network of Ontario percutaneous coronary intervention registry and linked to population-based administrative health databases. In the overall cohort, there was no difference in rates of target-vessel revascularization (P=0.47), myocardial infarction (P=0.71), or death (P=0.49). As compared with paclitaxel stents, the use of sirolimus stents was associated with a significantly lower 3-year rate of target-vessel revascularization in nondiabetic patients (8.3% versus 10.0%, P=0.01), but not in diabetic patients (12.7% versus 10.3%, P=0.07). Rates of all-cause mortality were similar in patients receiving sirolimus stents versus paclitaxel stents in both the diabetic (8.4% versus 9.2%, P=0.91) and nondiabetic (4.6% versus 3.0%, P=0.22) groups.. In this large observational study, patients receiving paclitaxel and sirolimus stents had similar mortality rates, but nondiabetic patients receiving sirolimus stents were significantly less likely to require repeat revascularization.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Artery Disease; Diabetic Angiopathies; Disease-Free Survival; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Ontario; Paclitaxel; Proportional Hazards Models; Registries; Sirolimus; Tubulin Modulators

Topics: Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Meta-Analysis as Topic; Myocardial Revascularization; Paclitaxel; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Sirolimus

The diabetic patient is at high risk of coronary heart disease. He/she can benefit of revascularisation procedures, even if he/she is exposed to a higher incidence of complications after a coronary artery bypass graft or a percutaneous transluminal coronary angioplasty. The use of drug-eluting stents--paclitaxel (PES) or sirolimus (SES)--dramatically reduces the risk of restenosis as compared to bare-metal stents; nevertheless, the rate of restenosis remains almost double in diabetic patients compared to that observed in non-diabetic subjects. However, the risk of (very) late thrombosis is higher with drug-eluting stents than with bare-metal stents, in the diabetic population as in the non-diabetic population. Altogether, among diabetic patients, the incidence of major cardiovascular events is significantly reduced with drug-eluting stents. This global clinical benefit essentially results from a diminution of revascularisation procedures rather than from a reduction of myocardial infarcts or cardiovascular deaths. Comparison between SES and PES gives discordant results. Indeed, while the loss of intra-stent lumen is more important with PES than with SES, PES are associated with a lower rate of major cardiovascular events than SES. Efficacious antiplatelet therapy in the long run is mandatory in all diabetic patients treated with drug-eluting stents.

Topics: Coronary Artery Disease; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Incidence; Paclitaxel; Postoperative Complications; Risk Assessment; Sirolimus; Thrombosis

Patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are at increased risk for adverse outcomes. The use of sirolimus eluting stents (SES) has been shown to improve outcomes in diabetic patients. Since results from randomized trials were derived from selected patients scientific scrutiny under real world conditions is necessary.. 1,948 patients with DM and 4,707 patients without DM were included in the German Cypher Registry, a post-marketing survey of use of SES in Germany. In >99% of entry cases a structured clinical follow-up was completed. By angiographic criteria severity of coronary artery disease was higher in diabetic patients compared to non-diabetics. However, procedural success and in-hospital complication rates were comparable between DM- and non-DM-patients. 6 months MACE rate in the DM group was significantly higher than in the non-DM group (16.4% vs. 13.0%) but lower than expected from historical data with the use of bare metal stents (BMS).. The results with SES in diabetics are encouraging but DM remains a risk factor for poor outcome of PCI. No statement is justified whether the treatment of diabetics with SES is at least as safe as bypass surgery. This intriguing question has to be answered in a direct randomized head-to-head comparison with state of the art surgery.

Topics: Aged; Angioplasty, Balloon, Coronary; Case-Control Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Cost-Benefit Analysis; Diabetes Mellitus; Diabetic Angiopathies; Drug-Eluting Stents; Equipment Safety; Female; Follow-Up Studies; Hospital Mortality; Humans; Middle Aged; Probability; Prospective Studies; Registries; Risk Assessment; Severity of Illness Index; Sirolimus; Statistics, Nonparametric; Survival Rate; Treatment Outcome

It is now emerging that, in patients who are at high risk for cardiovascular complications and, in particular, those with diabetes, the occurrence of late restenosis and thrombosis after treatment of coronary artery disease with drug-eluting stents is higher than earlier reports have suggested. Therefore, the aim of this study was to assess the prevalence of in-stent restenosis in a cohort of consecutive patients with diabetes treated for coronary disease in 2005 with drug-eluting stents [either sirolimus (58%) or paclitaxel (42%)]. The duration of follow-up was 9.0+/-3.4 months [mean+/-1 standard deviation (S.D.)]. A total of 154 patients (type 2 diabetes: 91%) were included in the study (age: 66+/-10 years), and the total number of implanted stents was 184. Two subjects died from cardiac causes, while myocardial infarction and (un)stable angina were observed in 3 (2%) and 39 (25%) patients, respectively. In-stent restenosis, appraised by angiography, was observed in 17 individuals (11%) after a mean follow-up of five months. Mean HbA(1c) in patients with restenosis was 7.6+/-1.8%. There was no difference in the rate of restenosis with sirolimus-(n=8) compared with paclitaxel-(n=9) eluting stents. Male gender, oral therapy for diabetes and stent diameter were predictors of in-stent restenosis. In conclusion, even over a medium-term period, in-stent restenosis remains a potential risk for coronary diabetic patients treated with drug-eluting devices.

Topics: Aged; Cohort Studies; Coronary Restenosis; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Retrospective Studies; Sirolimus; Survival Analysis; Treatment Outcome

This is a multicentre, open label, prospective non-randomized registry, with 9-month angiographic follow-up, conducted to evaluate the safety and effectiveness of drug-eluting stents (DES) when used in high restenosis risk patients from the real world.. From June 2004 to February 2005, a total of 1622 consecutive patients were enrolled to the Sicilian DES Registry, according to specific inclusion criteria. Both paclitaxel-eluting and sirolimus-eluting stents were used. The analysis was performed on 1472 patients because 150 patients were excluded from the study. The primary endpoint was to evaluate the rate of major adverse cardiac events (MACE) within 9 months after DES implantation. Major adverse cardiac events were defined as cardiac death, non-Q-wave or Q-wave myocardial infarction (MI) and target vessel revascularization (TVR). The secondary endpoints were procedural success, angiographic binary restenosis and stent thrombosis within 9 months post-procedure.. Patients were more frequently male; 472 (32.1%) were diabetics, of whom 130 (27.5%) were treated with insulin. Mean ejection fraction of the left ventricle was 51.5 +/- 8.7%. Multivessel disease was found and treated in 627 patients (42.6%). A total of 2439 lesions were treated with DES. Final angiographic success was achieved in 2422 (99.3%) lesions. Procedural success was achieved in 1422 (96.6%) patients. The 9-month cumulative incidence of MACE was 7.3% with 0.8% of cardiac deaths, 0.8% non-fatal MI, 7.9% TVR. Binary restenosis was observed in 101 patients (8.3%). Stent thrombosis was documented in 11 patients (0.8%).. Drug-eluting stents appear to be safe and associated with a low incidence of MACE at 9-month follow-up, even in patients selected for their complexity.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Registries; Sicily; Sirolimus

The long-term effectiveness of drug-eluting stents (DES) in unselected diabetics in routine practice is currently unclear.. To evaluate the long-term effectiveness of bare metal stents and DES in a real-world setting of diabetic patients, we analyzed 2-year follow-up data from all diabetic patients with de novo lesions enrolled in a prospective Web-based multicenter registry (Registro Regionale Angioplastiche dell'Emilia-Romagna; study period, 2002 to 2004) comprising all 13 hospitals performing percutaneous coronary interventions in the Emilia-Romagna region of Italy. Among the 1648 eligible patients treated with either bare metal stents alone (n=1089) or DES alone (n=559), 27% were insulin dependent and 83% had multivessel coronary disease. At 2 years, use of DES was associated with lower crude incidence of major adverse cardiac advents (all-cause mortality, nonfatal myocardial infarction, and target vessel revascularization) compared with bare metal stents (22.5% versus 28.1%; P=0.01). After propensity score adjustment, only target vessel revascularization appeared significantly lower in the DES group (11.6% versus 15.0%; hazard ratio, 0.66; 95% confidence interval, 0.46 to 0.96; P=0.041). Two-year angiographic stent thrombosis occurred in 1.5% DES patients and 0.7% of the bare-metal-stents patients (P=0.18). At Cox regression analysis, predictors of 2-year major adverse cardiac advents were left ventricular ejection fraction <35%, Charlson comorbidity index, insulin-dependent diabetes, and total lesion length.. In this large, real-world, diabetic population, the use of DES was associated with a moderate reduction in the 2-year risk of target vessel revascularization, a benefit that was limited to non-insulin-dependent diabetic patients. Larger long-term studies are needed to clarify the long-term effectiveness and safety of such devices in diabetic patients.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Combined Modality Therapy; Comorbidity; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Diabetes Mellitus; Diabetic Angiopathies; Female; Humans; Insulin; Italy; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Registries; Risk Factors; Sirolimus; Stents; Tacrolimus; Treatment Outcome

To investigate the outcome of a real world diabetic patient cohort treated with bare metal stents (BMS), sirolimus-, or paclitaxel-eluting stents (SES and PES, respectively). Due to the different mechanisms of action of both drugs it is currently unknown which device is the best option to treat these high-risk patients.. The study compares the 2-year clinical outcome of 708 consecutive diabetic patients (25% insulin treated) treated with either a BMS (n = 252), a SES (n = 206), or a PES (n = 250), as part of the RESEARCH and T-SEARCH registries. Target vessel revascularization was 19.5% in the BMS group, vs. 15.3% in the SES group and 9.7% in the PES group. PES (21.2%), but not SES (28.9%), were superior to BMS (29.7%) in reducing major adverse cardiac events. After propensity analyses, none of the differences remained significant. The incidence of stent thrombosis (ST) was high in both DES groups.. There was a trend towards a more favourable outcome associated with the use of PES over BMS. There was no significant difference between SES and PES in each of the clinical endpoints, and neither in the NIDDM patients, which are hypothesized to be better-off with PES.

Topics: Case-Control Studies; Coronary Restenosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Combinations; Drug Implants; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Paclitaxel; Retrospective Studies; Sirolimus; Stents; Survival Analysis

Vascular response at edges of drug-eluting stents is still not well established, particularly in diabetic patients who are prone to aggressive atherosclerosis progression. Recently, Biolimus and Zotarolimus have demonstrated potent antiproliferative effects.. To compare the vascular responses at edges of sirolimus analogous-eluting stents in patients with and without diabetes, using intravascular ultrasound (IVUS).. 306 edges were analyzed in 153 patients treated with drug-eluting stents and divided in: diabetics (122 edges) and nondiabetics (166 edges). IVUS was performed postintervention and at 6-month follow-up and included 5 mm distal and proximal to the stented segment. Vessel, lumen, and plaque volumes were calculated. Volume variation (follow-up minus basal) was also calculated. Edge restenosis was defined as obstruction >50%.. Baseline characteristics were similar between groups. In both groups the entire lesion length was covered (stent length/lesion length ratio was 1.5 for both groups). There were no differences in edge volumes and restenosis rate between the groups. Among diabetics, there was no significant volume variation. However, in nondiabetic patients there was significant increase in vessel volume in proximal (from 67.1 +/- 22 mm(3) to 72.2 +/- 25 mm(3): P = 0.02) and distal (from 54.4 +/- 22 mm(3) to 59.8 +/- 22 mm(3): P = 0.001) edges.. Nondiabetic patients showed a significant positive vascular remodeling in proximal and distal edges of sirolimus analogous-eluting stent. This vascular mechanism was not observed in diabetic patients. Although different vascular responses were observed, restenosis rates were equivalent between the 2 groups at 6-month follow-up.

Topics: Aged; Cardiovascular Agents; Case-Control Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Observational clinical studies have shown that patients with diabetes have less favorable results after percutaneous coronary intervention compared with the non-diabetic counterparts, but its mechanism remains unclear. The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process.. Diabetic porcine model was created with an intravenous administration of a single dose of streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation served as controls (control group). At 6 months, the degree of neointimal hyperplasia was determined by repeat coronary angiography, intravascular ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-alpha protein level in the aortic intima was evaluated by Western blotting, and TNF-alpha, interleukin (IL)-1beta and IL-6 mRNA levels were assayed by reverse transcription and polymerase chain reaction.. The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were comparable between the two groups. At 6-month follow-up, the degree of in-stent restenosis (40.4 +/- 24.0% vs. 20.2 +/- 17.7%, p < 0.05), late lumen loss (0.33 +/- 0.19 mm vs. 0.10 +/- 0.09 mm, p < 0.001) by quantitative angiography, percentage of intimal hyperplasia in the stented area (26.7 +/- 19.2% vs. 7.3 +/- 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 +/- 0.76 mm2 vs. 0.41 +/- 0.18 mm2, p < 0.05) by histological examination were significantly exacerbated in the diabetic group than those in the controls. Significant increases in TNF-alpha protein and TNF-alpha, IL-1beta and IL-6 mRNA levels were observed in aortic intima in the diabetic group.. Neointimal hyperplasia persisted at least up to 6 months after SES implantation in diabetic porcine, which may be partly related to an exaggerated inflammatory response within the blood vessel wall. Our results provide theoretical support for potential direct beneficial effects of anti-diabetic and anti-inflammation medications in reducing the risk of restenosis after stenting.

Topics: Animals; Catheters, Indwelling; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Disease Models, Animal; Hyperplasia; Male; Sirolimus; Stents; Swine; Tunica Intima

Drug-eluting stents have been developed to reduce the rates of restenosis after coronary angioplasty. Several studies have demonstrated that rapamycin eluting stents are reliable and effective.. To report the experience in our Health Centre with rapamycin-eluting stents.. Forty two stents with rapamicine were implanted to 32 diabetic patients, between June 2002 and December 2004. After the procedure, subjects were clinically followed-up for an average period of 19.9+/-9.9 months, evaluating functional capacity, angina pectoris, dyspnea, need for hospital admission, acute coronary events and cardiac death. In those subjects clinically suspected to have restenosis, a coronary angiography was performed.. Twenty-nine subjects (90.6%) remained asymptomatic, two subjects (6.3%) developed angina pectoris but restenosis was ruled out, and one subject (3.1%) died.. The use of rapamycin-eluting stents in these patients was safe and successful with no evidence of clinic restenosis. These positive results are similar to those reported in the Diabetes Study.

Topics: Angioplasty; Chi-Square Distribution; Coronary Restenosis; Coronary Stenosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Reproducibility of Results; Sirolimus; Treatment Outcome

We sought to assess the frequency and causes of stent thrombosis in diabetic and nondiabetic patients after implantation of sirolimus-eluting stents.. Safety concerns about late stent thrombosis have been raised, particularly when drug-eluting stents are used in less highly selected patients than in randomized trials.. The EVASTENT study is a matched multicenter cohort registry of 1,731 patients undergoing revascularization exclusively with sirolimus stents; for each diabetic patient included (stratified as single- or multiple-vessel disease), a nondiabetic patient was subsequently included. Patients were treated with aspirin + clopidogrel for at least 3 months and were followed for 465 (range 0 to 1,062) days (1-year follow-up in 98.5%). The primary end point was a composite of stent thrombosis (according to Academic Research Consortium definitions), cardiovascular death, and nonfatal myocardial infarction (major adverse cardiac events [MACE]).. During follow-up, MACE occurred in 78 patients (4.5%), cardiac death in 35 (2.1%), and stent thrombosis in 45 (2.6%): 30 definite, 23 subacute, and 22 late, including 9 at >6 months. In univariate analysis, the 1-year stent thrombosis rate was 1.8 times higher in diabetic than in nondiabetic patients (3.2% vs. 1.7%; log rank p = 0.03), with diabetic patients with multiple-vessel disease experiencing the highest rate and nondiabetic single-vessel disease patients the lowest (4.3% vs. 0.8%; p < 0.001). In multivariate analysis, in addition to the interruption of antithrombotic treatment, independent stent thrombosis predictors were previous stroke, renal failure, lower ejection fraction, calcified lesion, length stented, and insulin-requiring diabetes.. The risk of sirolimus stent thrombosis is higher for multiple-vessel disease diabetic patients.

Topics: Aged; Angioplasty, Balloon, Coronary; Antibiotics, Antineoplastic; Blood Vessel Prosthesis Implantation; Case-Control Studies; Coronary Disease; Diabetic Angiopathies; Disease-Free Survival; Drug Delivery Systems; Female; Humans; Insulin; Male; Middle Aged; Prospective Studies; Registries; Risk Factors; Sirolimus; Stents; Thrombosis; Treatment Outcome

Diabetes mellitus is associated with an increased risk of restenosis, stent thrombosis, and death after percutaneous coronary interventions. Little is known about the late outcome of patients with diabetes mellitus who receive drug-eluting stents (DES).. This study includes a prospective database of 2557 consecutive patients with coronary artery disease who underwent DES implantation in native coronary arteries in 2 German hospitals. The primary end points of the study were mortality and clinical restenosis (target lesion revascularization). Secondary end points were binary angiographic restenosis, stent thrombosis, and the composite of death or myocardial infarction.. Within a median follow-up period of 2.3 years, stent thrombosis occurred in 14 patients with diabetes versus 17 patients without diabetes: 3-year Kaplan-Meier estimates of stent thrombosis were 2.2% versus 1.0%, with a relative risk of 2.17 (95% CI 1.09-4.33, P = .027). Binary angiographic restenosis was observed in 87 patients with diabetes and 208 patients without diabetes (15.2% vs 13.5%, P = .32). Target lesion revascularization was needed in 93 patients with diabetes and 219 patients without diabetes (12.8% vs 12.0%, P = .56). There were 93 deaths among diabetic patients versus 118 deaths among nondiabetic patients: 3-year Kaplan-Meier estimates of mortality were 17.3% versus 7.8%, with a relative risk of 2.10 (95% CI 1.61-2.74, P < .001). After adjustment in the multivariable analyses, diabetes remained an independent predictor of 3-year mortality with a hazard ratio of 1.63 (95% CI 1.23-2.17, P < .001), but not of angiographic (P = .92) or clinical restenosis (P = .97).. Although DES attenuate diabetes-associated excess risk of restenosis, risk of death and thrombotic complications remains higher in patients with diabetes than in nondiabetic patients in the DES era.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Coronary Thrombosis; Diabetic Angiopathies; Follow-Up Studies; Humans; Immunosuppressive Agents; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Proportional Hazards Models; Risk Factors; Sirolimus; Stents; Survival Analysis; Treatment Outcome

Topics: Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Patients with metabolic syndrome (MS) are at increased risk for cardiovascular events. Although the number of patients with MS requiring coronary revascularization is increasing rapidly, the impact of MS on clinical events and restenosis in patients who undergo stent placement is not well defined. Seven hundred thirty-four consecutive patients with 734 de novo coronary lesions (<50 mm lesion length, reference vessel diameter <3.5 mm) were enrolled in this study. Four hundred thirty-seven patients were treated with bare-metal stents, and 297 patients were treated with sirolimus-eluting stents. Patients with bifurcation lesions, left main lesions, and ST-segment-elevation myocardial infarctions were excluded from the study. Patients were categorized into 3 groups: those with (1) diabetes mellitus (DM), (2) MS without DM, and (3) no MS and no DM. MS was defined according to American Heart Association and National Heart, Lung, and Blood Institute criteria (the presence of > or =3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, and increased fasting glucose). Clinical follow-up was performed for > or =1 year (mean 27.5 +/- 18.1 months). One hundred sixty-four patients (22%) had DM, 180 patients (25%) had MS without DM, and 390 patients (53%) had no MS and no DM. Baseline clinical and angiographic parameters were comparable among the 3 groups, including lesion length and reference vessel diameter. In patients treated with bare-metal stents, the rates of major adverse cardiac events (MACEs) at 12 months were 14% in patients without DM or MS, 18% in those with MS but no DM, and 33% in those with DM (p = 0.046). In patients treated with sirolimus-eluting stents, the MACE rates were 3% in patients without DM or MS, 4% in those with MS, and 13% in those with DM (p = 0.034). DM (odds ratio 2.14, 95% confidence interval 1.48 to 3.07, p <0.001) and bare-metal stent (odds ratio 2.51, 95% confidence interval 1.49 to 4.22, p <0.001) implantation were independent predictors of MACEs during follow-up, whereas MS was not predictive. Similarly, MS was not a predictor of target lesion revascularization. In conclusion, patients with MS did not have an increased risk for target lesion revascularization or a greater MACE rate compared with control patients during a 12 month follow-up period after bare-metal or drug-eluting stent placement. In contrast, DM is associated with significantly increased event rates.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetic Angiopathies; Female; Humans; Immunosuppressive Agents; Male; Metabolic Syndrome; Middle Aged; Retrospective Studies; Sirolimus; Stents

The objective of our study is to evaluate the long-term results of coronary angioplasty using active stents in a population of diabetic patients. This is a single-centre study on a consecutive series of 122 diabetic patients (40% of them insulin dependent) who between January 2003 and June 2004 underwent angioplasty with implantation of an active stent (sirolimus Cypher(R) or paclitaxel Taxus(R)) for one or more de novo coronary lesions. The mean age was 66 +/- 10 years and a total of 171 coronary segments were treated. The lesions treated were complex (type B2 + C) in 69% of the cases, with a mean stent length of 21 +/- 15 mm and a mean stent diameter of 2.7 +/- 0.3 mm. Follow-up at two years for 119 patients (3 lost to follow-up) revealed a mortality rate of 4.2%, and a myocardial infarction rate of 7.5%. The rates for revascularisation of the target lesion and the target vessel were 11.4% and 17.8% respectively, with a rate of major cardiac events of 22.5%. During this period, 25.2% of the patients underwent revascularisation of at least one vessel. This study confirms the benefits of using active stents for revascularisation of the target lesion in diabetic patients. However, it serves as a reminder that the progression of coronary atheroma is global, and that the prognosis for these patients depends essentially upon managing risk factors, and particularly on controlling their diabetes.

Topics: Aged; Coronary Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Paclitaxel; Sirolimus; Survival Analysis; Treatment Outcome

Endothelial dysfunction has been related both to progression of atherosclerotic disease and to future cardiovascular events. We assessed local epicardial endothelial function 6 months after sirolimus-eluting stent (SES) or bare metal stent (BS) implantation.. In 12 patients (seven SES, five BS), endothelium-dependent vasomotion of a coronary segment 15 mm in length, starting 2 mm distal to the stent, was assessed with quantitative coronary angiography immediately after the procedure and at 6 months follow-up, after intracoronary infusion of acetylcholine. Intravascular ultrasound (IVUS) was performed and coronary flow reserve (CFR) assessed in all patients. At follow-up significant vasoconstriction was seen in SES (median 32% diameter reduction from baseline) but not in BS (median 2% reduction) patients after acetylcholine infusion (P=0.03 for SES vs. BS); endothelium-independent vasodilatation to nitrates did not differ significantly between groups (20% SES, 5% BS, P=0.14). IVUS revealed no late unhealed dissections and CFR was comparable between groups (SES 3.1 vs. BS 3.2, n.s.).. SES implantation may have an adverse effect on local endothelium-dependent vasomotor responses compared with BS implantation at 6 months. Long-term clinical consequences of this observation are still unknown.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Vasospasm; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Nitroglycerin; Prospective Studies; Sirolimus; Stents; Vasodilation; Vasodilator Agents

An intraluminal echolucent tissue, dubbed "black hole," has been identified by intravascular ultrasonography after intracoronary brachytherapy. This study reports the characteristics and incidence of the black hole in patients treated with drug-eluting stent implantation using a sirolimus-eluting stent (SES). We included intravascular ultrasound data from the Compassionate Use of Sirolimus-Eluting Stent (SECURE, n = 61 lesions) registry, a study involving patients in whom previous brachytherapy had failed, and the DIABETES trial (n = 165 lesions), a multicenter, randomized study comparing SES versus bare metal stents in diabetic patients. Intravascular ultrasound follow-up was scheduled at 8 months (SECURE trial, post-brachytherapy population) and 9 months (DIABETES trial). In the SECURE population, a black hole was observed in 10 patients (19.6%). Seven black hole segments had significant intimal hyperplasia (> 10%). A black hole accounted for 27% of total intraluminal tissue. In the DIABETES trial, 2 patients (2.5%) in the SES group and none in the bare metal stent group showed echolucent intimal hyperplasia. In conclusion, a black hole occurred frequently after implantation of a SES in patients in whom intracoronary brachytherapy had previously failed. Black holes were also identified in a nonirradiated population, although the incidence was lower than in the post-brachytherapy patients. Bare metal stents were not associated with this phenomenon.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Brachytherapy; Coronary Disease; Coronary Vessels; Diabetic Angiopathies; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Sirolimus; Stents; Tunica Intima; Ultrasonography, Interventional

There is a clear need for a large multicentre trial comparing the efficacy of the two available drug eluting stents, sirolimus and paclitaxel, in diabetic patients with multivessel disease.

Topics: Catheterization; Coronary Stenosis; Diabetic Angiopathies; Drug Implants; Humans; Immunosuppressive Agents; Paclitaxel; Sirolimus; Stents

We sought to determine if the angiographic pattern of in-stent restenosis in drug-eluting stents (DES) maintains its prognostic importance.. The pattern of restenosis in the bare-metal stent era had a significant impact on therapeutic outcomes.. We identified a total of 250 consecutive restenotic lesions in 203 patients (66.4% sirolimus-eluting stents and 33.6% paclitaxel-eluting stents). We divided these lesions into two groups: focal, defined as < or =10 mm, 163 lesions (65.2%); and nonfocal, which were diffuse, proliferative, or obstructive, 87 lesions (34.8%). The end points analyzed were angiographic restenosis and target lesion revascularization (TLR).. Diabetes was the only clinical variable associated with the pattern of restenosis (28.8% focal compared with 52.9% diffuse; p = 0.0001). Angiographic follow-up of the treatment of restenosis was available in 61.2% of the lesions and was similar between the two groups. The rate of angiographic restenosis was 17.8% in the focal group and 51.1% in the nonfocal group (p = 0.0001). The incidence of TLR also increased with the type of restenosis treated (9.8% and 23%, respectively; p = 0.007). An adjusted multivariate analysis revealed that the pattern of restenosis remained associated with both the occurrence of restenosis and TLR (odds ratio [OR] 5.1 [95% confidence interval (CI) 1.1 to 23], p = 0.03; and OR 3.61 [95% CI 1.2 to 10.9], p = 0.02; respectively).. Similar to bare-metal stent data, the angiographic pattern of restenosis following DES implantation is prognostically important. Diabetes is a significant predictor of the pattern of restenosis in the DES era.

Topics: Combined Modality Therapy; Coronary Restenosis; Diabetic Angiopathies; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Paclitaxel; Prognosis; Prospective Studies; Sirolimus; Stents

This study sought to analyze the cost of percutaneous coronary interventions with use of sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) in patients at high risk of restenosis.. Recent studies have shown different clinical efficacy with these drug-eluting stents. Whether this difference extends on cost estimates between the 2 stents is not known.. We included 450 patients with diabetes mellitus and in-stent restenosis from 2 randomized studies comparing SES with PES. Assigned costs for the economic evaluation were the initial hospitalization and all subsequent cardiac-related inpatient/outpatient health resources during 9 to 12 months of clinical follow-up. The economic evaluation was performed from the health insurance system's perspective.. There were no differences between the 2 study groups regarding mortality (p = 0.78) and myocardial infarction rates (p = 0.76). Target lesion revascularization was performed in 16 patients (7.1%) in the SES group and in 34 patients (15.1%) in the PES group (p = 0.01). Initial hospital costs were not significantly different between the 2 stents (p = 0.53). The follow-up costs were, however, different: 2,684 +/- 2,072 euros per patient treated with SES and 4,527 +/- 6,466 euros per patient treated with PES (p < 0.001). Total costs also differed at the end of the follow-up: 8,924 +/- 3,077 euros per patient treated with SES and 10,903 +/- 7,205 euros per patient treated with PES (p < 0.001).. In patients at high risk of restenosis, use of SES is associated with lower costs compared with PES. The cost savings are mainly due to the reduced need of repeat revascularization procedures with SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Disease; Coronary Restenosis; Cost Savings; Costs and Cost Analysis; Diabetic Angiopathies; Female; Germany; Health Services; Hospital Costs; Hospitalization; Humans; Male; Middle Aged; Paclitaxel; Randomized Controlled Trials as Topic; Sirolimus

Topics: Coronary Restenosis; Diabetic Angiopathies; Disease-Free Survival; Drug Combinations; Drug Implants; Eptifibatide; Follow-Up Studies; Humans; Immunosuppressive Agents; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Sirolimus; Stents; Tirofiban; Tyrosine

The aim of this research was to evaluate the plaque prolapse (PP) phenomenon after bare-metal (BMS) and drug-eluting stent (DES) implantation in patients with diabetes mellitus using 3-dimensional volumetric intravascular ultrasound (IVUS).. Plaque prolapse has been observed in up to 22% of patients treated with BMS. Diabetic patients have a larger atherothrombotic burden and may be more prone to have PP. However, the incidence of PP and its clinical impact after DES implantation is unknown.. Three-dimensional IVUS was performed after intervention and at 9-month follow-up in 168 patients with diabetes (205 lesions) treated with bare BX Velocity stents ((BX Velocity/Sonic, Cordis, Johnson & Johnson) (BMS, n = 65), sirolimus-eluting stents (Cypher, Cordis) (SES, n = 69), and paclitaxel-eluting stents (Taxus, Boston Scientific, Natick, Massachusetts) (PES, n = 71). Intravascular ultrasound data at the sites of PP were compared with stented segments without PP in each lesion. Outcomes were evaluated at 9- and 12-month follow-up.. There were 42 sites of PP (BMS = 11, SES = 11, PES = 20, p = NS) in 34 stented segments of 205 (16.6%) lesions. Plaque prolapse was more frequent in the right coronary artery and in chronic total occlusion lesions. Post-procedure PP volume was 1.95 mm3 in BMS, 2.96 mm3 in SES, and 4.53 mm3 in PES. At follow-up, tissue volume increased at PP sites in both BMS and PES, but not after SES. Neointimal proliferation was similar between PP and non-PP sites. Stent thrombosis and restenosis rates were similar between PP and non-PP lesions.. The incidence of PP after implantation of new generation tubular stents in patients with diabetes remains high. Drug-eluting stent implantation was not associated with increased risk of PP. Plaque prolapse was not associated with stent thrombosis or increased neointimal proliferation.

Topics: Aged; Chronic Disease; Coronary Disease; Coronary Stenosis; Diabetic Angiopathies; Drug Delivery Systems; Equipment Design; Female; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Male; Metals; Middle Aged; Multicenter Studies as Topic; Paclitaxel; Prolapse; Randomized Controlled Trials as Topic; Risk Assessment; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

Diabetic patients frequently have small-diameter vessels, which increases their risk of restenosis. The aim of this study was to determine the efficacy of sirolimus-eluting stent implantation in these high-risk patients following percutaneous coronary intervention.. Our study population comprised a subset of 85 diabetic patients from the DIABETES (DIABETes and sirolimus Eluting Stent) trial who had very small vessels, defined as those with a reference diameter < or =2.25 mm. In the 100 lesions treated, 49 sirolimus-eluting stents and 51 bare-metal stents were used. Glycoprotein IIb/IIIa inhibitors were used as recommended by the protocol and dual antiplatelet therapy was administered for 1 year.. Baseline clinical and angiographic characteristics were comparable in the two groups. The patients' mean age was 66 (9) years, 42% were women, and 37% were insulin-dependent. On average, the lesion length was 15.0 (9.0) mm and the reference diameter was 1.9 (0.2) mm. At 9-month follow-up, both late lumen loss and the restenosis rate were significantly lower in the sirolimus-eluting stent group than in the bare-metal stent group, at -0.03 (0.3) mm vs 0.44 (0.5) mm (P< .001), and 9.1% vs 39.1% (P=.001), respectively. These differences were also observed in the subgroup of insulin-dependent patients. At 1-year follow-up, the stent thrombosis rate was 0% in the sirolimus-eluting stent group, whereas two patients in the bare-metal stent group presented with stent thrombosis.. Sirolimus-eluting stent implantation in diabetics with very small vessels is safe and effective, even in insulin-dependent patients.

Topics: Aged; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Clinical Trials as Topic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Data Interpretation, Statistical; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Patient Selection; Platelet Aggregation Inhibitors; Risk Factors; Sirolimus; Stents; Survival Analysis; Time Factors; Ultrasonography; Video Recording

Restenosis rate is lower after sirolimus-eluting stent (SES) implantation than after bare metal stent (BS) implantation. We evaluated the impact of SES implantation on immediate and 12-month outcome in diabetic patients with multivessel coronary artery disease (MVD).. From April 2002 to September 2003, 100 consecutive diabetic patients with MVD without previous myocardial revascularization underwent successful elective percutaneous coronary intervention (PCI) with SES on native coronary arteries at our institutions. A group (n = 122) of consecutive diabetic patients with MVD treated with BS implantation (BS group) for de novo lesions was selected from our database and matched with the SES group. Major adverse cardiac events (MACEs) during hospital stay and at follow-up included nonfatal myocardial infarction, death, bypass surgery, and re-PCI.. At 12 +/- 4 months, MACEs occurred in 25% of patients in the SES group and in 44% of those in the BS group (P = .003, OR .72, 95% CI 0.57-0.91). Need for repeat intervention (re-PCI or bypass surgery) occurred in 17% of patients in the SES group and in 41% of those in the BS group (P < .001, OR .67, 95% CI 0.52-0.86). No significant difference in the rate of death and myocardial infarction was observed. In the SES group, the independent predictors of MACEs at follow-up were premature clopidogrel discontinuation (hazard ratio 20.62, 95% CI 1.60-264.97, P = .020) and chronic renal insufficiency (hazard ratio 4.73, 95% CI 1.99-11.25, P = .0004).. As compared with BS implantation, SES implantation favorably influences outcome in diabetic patients with MVD, mainly by reducing the need for new revascularization.

Topics: Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Carriers; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Postoperative Complications; Sirolimus; Stents; Time Factors

In the treatment of coronary stenosis, evolution after PTCA is not as good in diabetic patients compared to non diabetic ones, whatever the treatment used. We now have data of large clinical studies which show good results of drug loaded stents in diabetic patients, especially with either a cytostatic drug (sirolimus) or a cytotoxic one (paclitaxol). In the RAVEL study, among the 44 diabetic patients, 19 had sirolimus stenting with a restenosis rate of 0% vs a restenosis rate of 40% for the 25 patients with standard stents. In the 279 diabetic patient group of the SIRIUS study, the restenosis rate (50% or more stenosis rate) was 17.6% when sirolimus stenting was used vs 50.5% for the patients with standard stenting and at 9 months and target lesion revascularisation was from 22.3% with bare metal stents, compared to 6.9% with sirolimus eluting stents. In the TAXUS IV study, the advantage was evident in diabetic patients with a restenosis rate 80% lower in patients treated with oral anti diabetic therapy and 82% in patients treated with insulin. In the TAXUS VI study, the target lesion revascularisation rate of diabetic patients was 2.6% when taxus MR (modified release) was used, vs 22.6% with standard stents. The event which until now made PTCA different from surgery was restenosis, especially in diabetic patients. The analysis of use of recent active stenting registries has shown that diabetic patients have now much better long term results than previously reported.

Topics: Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Humans; Immunosuppressive Agents; Sirolimus; Stents

Drug-eluting stents are designed to reduce the risk of major adverse cardiac events after percutaneous coronary intervention by inhibiting cellular proliferation and reducing restenosis of the coronary artery. In high-risk lesions, drug-eluting stents may limit restenosis and the need for repeat revascularization. In optimal lesions, they may eliminate restenosis completely. Drug-eluting stents have made percutaneous intervention a safe and definitive treatment for coronary artery disease.

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

Topics: Clinical Trials as Topic; Coronary Restenosis; Diabetic Angiopathies; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Sirolimus; Treatment Outcome

Drug eluting stents have been shown to reduce the rate of in-stent restenosis in cases where single lesions are treated. The performance of these stents, in patients with multivessel disease and complex lesions, however, remains unknown. Our experience with sirolimus eluting stents in such patients is presented.. This study includes all consecutive patients treated at San Raffaele Hospital and EMO Centro Cuore Columbus, Milan, Italy treated with sirolimus eluting stents.. Between April 2002 and March 2003, 486 patients with 1027 lesions were treated (437 males, 49 females) with a mean (SD) age of 62.2 (10.5) years. Of all patients studied, 19.1% had single vessel disease, 33.8% had two vessel disease, and 47.1% had three vessel disease. Of the whole study group, 20.3% of patients had diabetes mellitus. A mean (SD) of 2.3 (0.4) stents per patient and 1.1 (0.2) stents per lesion were implanted. The baseline mean reference diameter was 2.7 (0.6) mm with a mean minimal luminal diameter of 0.9 (0.5) mm. Post-stenting, the acute gain was 1.8 (0.6) mm. During hospital stay one patient died (0.2%) and 13 (2.7%) patients had in-hospital myocardial infarction (MI). One patient required urgent repeat percutaneous coronary intervention. Six months clinical follow up was performed in all 347 eligible patients. Six months mortality was 2.0% (n = 7) and acute MI occurred in 0.3% (n = 1). Target lesion revascularisation occurred in 9.5% (n = 33) of the patients and target vessel revascularisation (TVR) in 11.5% (n = 40) of the patients. Major adverse cardiac event rate was 13.8% (n = 48). TVR was 4.5% for single vessel disease and 13.2% for multivessel disease. Diabetes mellitus was the only significant predictor for TVR.. The use of drug eluting stents in single and multivessel coronary disease produces good short and medium term results with a low rate of revascularisation. Longer term follow-up is required to confirm these observations.

Topics: Adult; Aged; Aged, 80 and over; Coronary Restenosis; Diabetic Angiopathies; Drug Implants; Female; Humans; Immunosuppressive Agents; Length of Stay; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Platelet Glycoprotein GPIIb-IIIa Complex; Retrospective Studies; Sirolimus; Stents; Survival Analysis; Treatment Outcome

For recurrent in-stent restenosis (ISR), surgical revascularization or brachytherapy is still the principal therapeutic options. The present investigation explores the efficacy of a sirolimus-eluting stent to prevent restenosis in these lesions with a high risk of recurrence. In 22 consecutive patients with a recurrent and diffuse ISR, a sirolimus-eluting stent was implanted to cover the restenotic lesion. All patients were followed clinically for at least 1 year and underwent a repeat angiography after 7 months. A quantitative coronary angiographic analysis was done. The target vessel failure was 14% in the sirolimus-eluting stent group, with an angiographic late loss of only 0.39 +/- 0.54. No subacute stent thrombosis was observed, and the 1-year event-free survival was 86%. The three cases with restenosis were all focal and could be successfully treated by additional drug-eluting stent implantation. This study showed the efficacy of a sirolimus-eluting stent for the prevention of restenosis in a worst-case scenario of recurrent and diffuse ISR. The observed restenosis rate is lower than that reported after brachytherapy and suggests that sirolimus-eluting stents are a promising treatment option for ISR.

Topics: Aged; Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Recurrence; Sirolimus; Stents

Topics: Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Restenosis; Coronary Stenosis; Diabetic Angiopathies; Humans; Immunosuppressive Agents; Risk Factors; Sirolimus; Stents

Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration.

Topics: Adult; Calcineurin Inhibitors; Child; Diabetic Angiopathies; Endothelium, Vascular; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Sirolimus; Thrombosis