zotarolimus and Diabetes-Mellitus

Diabetes mellitus (DM) and cardiovascular diseases often co-exist. Today, percutaneous coronary intervention (PCI) is the preferred revascularization procedure for majority of patients with coronary artery disease. Polymer-free amphilimus-eluting stents (AES) represent a novel elution technology in the current era of drug-eluting stents. In this analysis, we aimed to systematically compare the cardiovascular outcomes which are associated with polymer-free amphilimus-eluting stents (AES) versus the durable polymer zotarolimus-eluting stents (ZES) for the treatment of patients with DM.. Http://www.. gov, EMBASE, Web of Science, MEDLINE, Cochrane database and Google Scholar were searched for publications comparing polymer-free AES versus durable polymer ZES in patients with DM. Selective cardiovascular outcomes were assessed. Statistical analysis was carried out by the latest version of the RevMan software. Risk ratio (RR) with 95% confidence interval (CI) was used to represent the data analysis.. Four studies with a total number of 1795 participants with DM whereby 912 patients were assigned to be revascularized by the polymer-free AES and 883 patients were assigned to be revascularized by the durable polymer ZES were included in this analysis. In patients with DM, at one year, polymer-free AES were associated with significantly lower risk of major adverse cardiac events (MACEs) (RR: 0.69, 95% CI: 0.54-0.88; P = 0.002) and target lesion failure (TLF) (RR: 0.66, 95% CI: 0.48-0.91; P = 0.01) compared to durable polymer ZES. However, there was no significant change in all-cause mortality (RR: 0.79, 95% CI: 0.51-1.22; P = 0.28), cardiac death and the other cardiovascular outcomes. Similar risk of total stent thrombosis (RR: 1.13, 95% CI: 0.60-2.13; P = 0.70), including definite stent thrombosis (RR: 1.12, 95% CI: 0.38-3.31; P = 0.84), probable stent thrombosis (RR: 0.87, 95% CI: 0.37-2.09; P = 0.76), possible stent thrombosis (RR: 1.19, 95% CI: 0.50-2.87; P = 0.69) and late stent thrombosis (RR: 1.00, 95% CI: 0.17-5.72; P = 1.00) as between polymer-free AES and durable polymer ZES in patients with DM.. At 1 year follow-up, polymer-free AES were associated with significantly lower MACEs and TLF compared to durable polymer ZES in these patients with DM, without any increase in mortality, stent thrombosis and other cardiovascular outcomes. However, this analysis is only based on a follow-up time period of one year, therefore, future research should focus on the long term follow-up time period.

Topics: Cardiovascular Agents; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Risk Factors; Treatment Outcome

Patients with diabetes and coronary artery disease remain at high risk for adverse cardiovascular events after percutaneous coronary intervention. The efficacy and safety of the various drug-eluting stents (DES) in patients with diabetes is unclear.. Randomized controlled trials comparing first-generation DES [paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES)] with everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in diabetic patients were systematically searched. Efficacy [target vessel revascularization (TVR) and target lesion revascularization (TLR)] and safety [major adverse cardiac events (MACE), all-cause and cardiac mortality, myocardial infarction, stent thrombosis] outcomes were evaluated.. Eighteen randomized controlled trials comprising of 8095 patients (17,000 patient-years of follow-up) were included. Compared to first-generation DES, EES significantly decreased MACE by 18% (relative risk [RR]: 0.82, 95% confidence interval [CI]: 0.70-0.96), myocardial infarction by 43% (RR: 0.57, 95% CI: 0.39-0.84) and stent thrombosis by 46% (RR: 0.54, 95% CI: 0.35-0.82) in patients with diabetes. Moreover EES showed a trend towards reduction in rates of TLR and TVR (p=0.05). ZES was associated with 89% increased risk for TLR (RR: 1.89, 95% CI: 1.10-3.22) compared to first-generation DES. Furthermore, meta-regression analysis showed a greater magnitude of benefit of EES over first-generation DES for MACE (p=0.037) and stent thrombosis (p=0.036) in diabetic patients requiring Insulin.. In patients with diabetes and coronary artery disease undergoing stenting, EES is the most efficacious and safe DES. The outcomes data for ZES in diabetes patients were limited and further trials are needed.

Topics: Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Sirolimus; Treatment Outcome

The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes.. The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes.. We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years.. The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%).. The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Device Approval; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Hypoglycemic Agents; Insulin; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; United States; United States Food and Drug Administration

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

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

To relate late lumen loss (LLL) after drug-eluting stent (DES) implantation to angiographic (BAR) and target vessel revascularization (TVR) in randomized clinical trials of DES.. We reviewed all clinical trials comparing different DES and having protocol-driven angiographic follow-up. We combined the data in a meta-regression analysis correlating LLL with BAR or TVR, with and without adjustment for diabetes mellitus, lesion length or reference vessel diameter. There were 15,846 patients in 29 trials (9 DES platforms) and 8697 had angiographic follow-up at a mean of 8 months. The mean age was 63 y, 28% were women and 33% had diabetes mellitus. Mean weighted in-segment LLL was 0.232mm (0.228-0.235mm), significantly higher in paclitaxel- and zotarolimus-eluting stents than in sirolimus-, everolimus- or biolimus-eluting stents. LLL was monotonically related to BAR (BAR=0.30×LLL+0.02, R(2)=0.53, P<0.0001) and TVR (TVR=0.20×LLL+0.02, R(2)=0.46, P<0.0001). Two thirds of patients with BAR had TVR. LLL remained significantly associated with BAR and TVR after multivariable adjustment. Reference vessel diameter and diabetes mellitus were inversely related to BAR.. LLL is a strong, monotonically related predictor of BAR and TVR. There is no evidence of threshold phenomenon in these relationships.

Topics: Aged; Angiography; Diabetes Complications; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Paclitaxel; Randomized Controlled Trials as Topic; Regression Analysis; Sirolimus

The elevated risk of adverse events following percutaneous coronary intervention in diabetic patients persists with newer-generation DES. The polymer-free amphilimus-eluting stent (PF-AES) possesses characteristics with a potentially enhanced performance in patients with diabetes. Data from the 1-year follow-up period has been previously published. The aim of this subanalysis was to assess long-term performance of two contemporary drug-eluting stents (DES) in a diabetic population.. In the ReCre8 trial, patients were stratified for diabetes and troponin status, and randomized to implantation of a permanent polymer zotarolimus-eluting stent (PP-ZES) or PF-AES. The primary endpoint was target-lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. Clinical outcomes between discharge and 3 years follow-up were assessed.. A total of 302 patients with diabetes were included in this analysis. After 3 years, TLF occurred in 12.5% of PP-ZES patients versus 10.0% in PF-AES patients (p = 0.46). Similarly, the separate components of TLF were comparable between the two study arms. The secondary composite endpoint of NACE was higher in the PP-ZES arm with 45 cases (29.6%) versus 30 cases (20.0%) in the PF-AES arm (p = 0.036). In the insulin-dependent diabetic population, TLF occurred in 19.1% of PP-ZES patients versus 10.4% of PF-AES patients (p = 0.21). NACE occurred in 40.4% of PP-ZES patients versus 27.1% of PF-AES patients (p = 0.10).. This subanalysis shows that the use of PF-AES results in similar clinical outcomes as compared to PP-ZES, yet some benefits of use of PF-AES in diabetic patients may prevail. Future dedicated trials should confirm these findings.

Topics: Cardiovascular Agents; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Follow-Up Studies; Humans; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Treatment Outcome

Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes.. We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44-0.96; Pnon-inferiority < 0.001; Psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46-0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups.. In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome.. ClinicalTrials.gov: NCT03321032.

Topics: Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Treatment Outcome

Topics: Adolescent; Adult; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Humans; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Treatment Outcome

Very long-term outcomes according to diabetic status of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) with new-generation drug-eluting stents (DES) are scant. Both, the durable polymer zotarolimus-eluting stent (DP-ZES), the first DES to gain FDA-approval for specific use in patients with diabetes mellitus, and the polymer-free sirolimus- and probucol-eluting stent (PF-SES), with a unique design that enables effective drug release without the need of a polymer offer the potential to enhance clinical long-term outcomes especially in patients with diabetes mellitus.. We investigate 10-year clinical outcomes of the prespecified subgroups of patients with and without diabetes mellitus, randomly assigned to treatment with PF-SES versus DP-ZES in the ISAR-TEST 5 trial. The primary endpoint of interest was major adverse cardiac events (MACE), defined as the composite of all-cause death, any myocardial infarction or any revascularization. Further endpoints of interest were cardiac death, myocardial infarction related to the target vessel and target lesion revascularization as well as the individual components of the primary composite endpoint and the incidence of definite or probable stent thrombosis at 10 years.. This analysis includes a total of 3002 patients randomly assigned to PF-SES (n = 2002) or DP-ZES (n = 1000). Prevalence of diabetes mellitus was high and comparable, 575 Patients (28.7%) in PF-SES group and 295 patients (29.5%) in DP-ZES group (P = 0.66). At 10 years 53.5% of patients with diabetes mellitus and 68.5% of patients without diabetes mellitus were alive. Regarding major adverse cardiac events, PF-SES as compared to DP-ZES showed comparable event rates in patients with diabetes mellitus (74.8% vs. 79.6%; hazard ratio 0.86; 95% CI 0.73-1.02; P = 0.08) and in patients without diabetes (PF-SES 62.5% vs. DP-ZES 62.2%; hazard ratio 0.99; 95% CI 0.88-1.11; P = 0.88).. At 10 years, both new-generation DES show comparable clinical outcome irrespective of diabetic status or polymer strategy. Event rates after PCI in patients with diabetes mellitus are considerable higher than in patients without diabetes mellitus and continue to accrue over time.. ClinicalTrials.gov, NCT00598533, Registered 10 January 2008, https://clinicaltrials.gov/ct2/show/NCT00598533?term=NCT00598533 Kaplan-Meier estimates of endpoints of interest for patients with vs. without diabetes mellitus treated with PF-SES vs. DP-ZES. Bar graphs: Kaplan-Meier estimates as percentages. PF-SES: polymer-free sirolimus-eluting stent; DP-ZES: durable polymer zotarolimus-eluting stent; DM: diabetes mellitus. Comparison of event rates of individual endpoints in patients with and without diabetes mellitus treated with PF-SES vs. DP-ZES all without statistically significant differences. Comparison of event rates of individual endpoints in overall patients with vs. without diabetes mellitus significantly different (P ≤ 0.01 for all comparisons).

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Polymers; Probucol; Sirolimus; Treatment Outcome

We compared 10-year clinical outcomes in diabetes and nondiabetes patients treated with Endeavor zotarolimus-eluting (ZES) or Cypher sirolimus-eluting coronary stents (SES). A total of 1,162 patients were randomized to ZES (169 with diabetes) and 1,170 patients were randomized to SES (168 with diabetes). Patients were further stratified by diabetes status at the time of inclusion. A subgroup of patients with diabetes (n = 88) underwent angiographic re-evaluation 10 months after stent implantation. End points included a combined end point of death or myocardial infarction, and the individual end points of death, myocardial infarction, and revascularization. In patients with diabetes, we found no difference in the combined end point (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.53 to 1.24), death (OR 0.80, 95% CI 0.51 to 1.25), or in MI (OR 1.07, 95% CI 0.60 to 1.91). However, diabetics with ZES more frequently underwent coronary revascularization compared with SES patients (OR 1.93, 95% CI 1.05 to 3.66). In patients without diabetes, ZES and SES had similar 10-year rates of all end points (death: OR 1.13, 95% CI 0.93 to 1.39; MI: OR 0.80, 95% CI 0.61 to 1.05; revascularization: OR 0.81, 95% CI 0.61 to 1.09). Landmark analysis from 5 to 10 years showed no difference in outcomes between SES and ZES in either subgroup. In conclusion, at 10 years, SES and ZES performed similarly in patients with and without diabetes. Although coronary revascularization was more prevalent in diabetes patients with ZES, this may, in part, have been related to the angiographic follow-up that was offered to a subgroup of diabetes patients.

Topics: Cause of Death; Coronary Angiography; Coronary Artery Disease; Denmark; Diabetes Mellitus; Drug-Eluting Stents; Follow-Up Studies; Forecasting; Humans; Immunosuppressive Agents; Incidence; Postoperative Complications; Retrospective Studies; Risk Assessment; Sirolimus; Survival Rate

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

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

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

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

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

The prevalence of factors that are associated with an increased risk of stent thrombosis (ST), including smoking, diabetes mellitus, and small stent size, is different in women and men who underwent percutaneous coronary intervention. Thus, gender may potentially modify the relation between stent type and the incidence of ST during long-term follow-up. We explored the data of Patient Related Outcomes With Endeavor Versus Cypher stenting Trial (PROTECT) to evaluate this hypothesis. PROTECT randomized 2,061 women and 6,648 men who underwent percutaneous coronary intervention for various indications to Endeavor zotarolimus-eluting stenting (E-ZES) or Cypher sirolimus-eluting stenting (C-SES). Dual antiplatelet therapy was prescribed for at least 3 months. Data on study end points were collected until 5 years after randomization, including ST, death, and cardiovascular events. We analyzed end points and treatment effect (E-ZES vs C-SES) in relation to gender. Women were on average 4.7 years older (65.8 vs 61.1), had a higher prevalence of insulin-dependent diabetes mellitus, were less often smokers, and had a shorter total stent length than men. At discharge and throughout follow-up, a slightly lower fraction of women were using dual antiplatelet therapy. During 5-year follow-up, definite or probable ST was observed in 36 women (1.8%) and 152 men (2.4%; log-rank p = 0.15). E-ZES reduced the incidence of ST compared with C-SES in women (hazard ratio 0.58) and men (hazard ratio 0.61), with no evidence of heterogeneity (p = 0.89). In conclusion, in PROTECT, women and men had similar cumulative incidence of ST at 5 years after stent placement. The favorable effect of the study stent E-ZES over C-SES was not modified by gender.

Topics: Aged; Antibiotics, Antineoplastic; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Sex Factors; Sirolimus; Thrombosis; Treatment Outcome

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

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

Drug-eluting stents (DES) were first used on-label - in simple patients with low clinical risk and easily accessible lesions. Currently, DES are increasingly used off-label - in complex patients undergoing percutaneous coronary interventions (PCI) with historically higher event risk. Therefore, our aim was to investigate whether patients with off-label indications for DES use had similar outcomes compared to patients who were treated for on-label indications only. We analysed two-year follow-up data of 1,387 TWENTE trial patients, treated with second-generation everolimus-eluting XIENCE V or zotarolimus-eluting Resolute stents, and compared off-label vs. on-label DES use with regard to the following clinical endpoints: cardiac death, myocardial infarction (MI), periprocedural MI (≤48 hrs), and target vessel revascularisation (TVR). Patients with off-label DES use (n=1,033; 74.5%) had more diabetes (22.9% vs. 17.5%; p=0.032), previous MI (35.9% vs. 22.3%; p<0.001), type B2/C lesions (84.7% vs. 62.7%; p<0.001), and acute coronary syndromes (57.8% vs. 33.3%; p<0.001). Nevertheless, cardiac death and TVR rates were similar to those of patients with on-label DES use (p>0.8). Following off-label DES use, there was a higher incidence of PMI (5.0% vs. 1.4%; p=0.003), of which only 1.1% reached creatine kinase levels >5x the upper limit of normal (ULN). Despite differences in risk profile, patients with off-label DES use did not differ from patients with on-label DES use in clinical endpoints other than periprocedural MI. These largely positive findings underline the favourable safety profile of second-generation DES.

Topics: Acute Coronary Syndrome; Calcinosis; Creatine Kinase; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Off-Label Use; Patient Outcome Assessment; Percutaneous Coronary Intervention; Severity of Illness Index; Sirolimus

Angiographic and clinical outcomes remain relatively unfavorable for diabetic patients even after the use of drug-eluting stent. This prospective, multicenter, randomized study compared the relative efficacy and safety of resolute zotarolimus-eluting stent (R-ZES) and sirolimus-eluting stent (SES) implantation in diabetic patients with coronary artery disease. The primary end point was noninferiority of angiographic in-segment late loss at 9 months. Clinical events were also monitored for at least 12 months. Patient recruitment was prematurely stopped after enrollment of 256 patients (127 in R-ZES group and 129 in SES) because of discontinuing production of SES. The R-ZES was noninferior to the SES for 9-month in-segment late loss (0.34 ± 0.30 vs 0.39 ± 0.43 mm; difference -0.048; 95% confidence interval -0.157 to 0.061; upper 1-sided 95% confidence interval 0.044; p <0.001 for noninferiority). In addition, in-stent late loss (0.22 ± 0.29 vs 0.21 ± 0.40 mm, p = 0.849) and the rates of in-segment (1.2% vs 6.7%, p = 0.119) and in-stent (1.2% vs 3.3%, p = 0.621) binary restenoses were similar between the 2 groups. At 12 months, there were no statistical differences between the 2 groups in the incidence of any clinical outcomes (death, myocardial infarction, stent thrombosis, ischemia-driven target lesion revascularization, ischemia-driven target vessel revascularization, and composite outcomes). In conclusion, despite having reduced power because of early study termination, our study suggests that the R-ZES has noninferior angiographic outcomes at 9 months to the SES in diabetic patients with coronary artery disease.

Topics: Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Prosthesis Design; Sirolimus; Treatment Outcome

To evaluate the differential treatment effects of zotarolimus-eluting stents (ZES), sirolimus-eluting stents (SES), and paclitaxel-eluting stents (PES) according to diabetic status.. Diabetic patients have a higher risk of ischemic complications after stenting than nondiabetic patients.. Using data from the ZEST randomized trial, comparing ZES with SES and PES, we evaluated relative outcomes among stents in diabetic and nondiabetic patients. The primary outcome was a major adverse cardiac event (MACE), defined as a composite of death, myocardial infarction, or ischemia-driven target-vessel revascularization.. Of the 2,645 patients enrolled in the ZEST trial, 760 (29%) had diabetes mellitus. Baseline clinical and angiographic characteristics were similar in the three stent groups, regardless of diabetic status. In diabetic patients, ZES showed similar rates of MACE as compared to PES (13.8% vs. 15.3%, P = 0.58), but higher rates of MACE than SES (13.8% vs. 7.7%, P = 0.05). In nondiabetic patients, ZES showed similar rates of MACE as compared to SES (10.3% vs. 10.8%, P = 0.72), whereas significantly lower rates of MACE compared to PES (10.3% vs. 15.3%, P = 0.01). In comparing the ZES and SES groups, there was a substantial interaction between diabetic status and stent types on MACE occurrence (Interaction P = 0.07). However, in comparison of ZES and PES, there were no significant interactions between diabetes and stent type on MACE (Interaction P = 0.25).. In diabetic patients, SES showed the lowest rate of MACE compared with ZES and PES. But, in nondiabetic patients, SES and ZES showed significantly lower rates of MACE than PES. ZES shows a diabetes-related interaction on MACE compared with SES, but not with PES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Republic of Korea; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

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

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

Diabetes is associated with an increased risk of major adverse cardiac events after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus treated with the second-generation Endeavor zotarolimus-eluting stent (ZES) or the first-generation Cypher Select+ sirolimus-eluting stent (SES). We randomized 2,332 patients to treatment with ZESs (n = 1,162, n = 169 diabetics) or SESs (n = 1,170, n = 168 diabetics) and followed them for 18 months. Randomization was stratified by presence/absence of diabetes. The primary end point was major adverse cardiac events defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Secondary end points included these individual end points plus all-cause mortality and target lesion revascularization. In diabetic patients, use of ZES compared to SES was associated with an increased risk of major adverse cardiac events (18.3% vs 4.8%, hazard ratio 4.05, 95% confidence interval 1.86 to 8.82), myocardial infarction (4.7% vs 0.6%, hazard ratio 8.09, 95% confidence interval 1.01 to 64.7), target vessel revascularization (14.2% vs 3.0%, hazard ratio 4.99, 95% confidence interval 1.90 to 13.1), and target lesion revascularization (12.4% vs 1.2%, hazard ratio 11.0, 95% confidence interval 2.59 to 47.1). In patients without diabetes differences in absolute risk decrease were smaller but similarly favored SES. In conclusion, implantation of ZESs compared to SESs is associated with a considerable increased risk of adverse events in patients with diabetes at 18-month follow-up.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Retreatment; Risk Assessment; Sirolimus

Patients with diabetes have more extensive coronary disease, resulting in higher risks of adverse clinical events following stenting. In all-comer patients, contemporary DES have shown excellent safety and efficacy, but data on diabetic patients are scarce. Separately for the BIO-RESORT and BIONYX trials, we assessed the 2-year clinical outcomes of diabetic patients, treated with various contemporary drug-eluting stents (DES).. We performed two prespecified secondary analyses of two randomized DES trials, which both stratified for diabetes. The main endpoint was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. Follow-up was finished before the COVID-19 pandemic.. In BIO-RESORT, 624/3514 (17.8%) had diabetes: 211 received Orsiro sirolimus-eluting stents (SES), 203 Synergy everolimus-eluting stents (EES), and 210 Resolute Integrity zotarolimus-eluting stents (RI-ZES). TVF did not differ between SES (10.2%) and EES (10.0%) versus RI-ZES (12.7%) (SES vs. RI-ZES HR:0.78, 95%-CI [0.44-1.40]; p = 0.40, EES vs. RI-ZES HR:0.79, 95%-CI [0.44-1.40]; p = 0.42). In BIONYX, 510/2488 (20.5%) patients had diabetes: 250 received SES and 260 Resolute Onyx zotarolimus-eluting stents (RO-ZES). There was no difference in TVF between SES (10.7%) versus RO-ZES (12.2%) (HR:0.88, 95%-CI [0.52-1.48]; p = 0.63).. There was no difference in 2-year clinical outcome among patients with diabetes, who were treated with SES, or EES, versus RI-ZES. In addition there was no difference in clinical outcome in diabetic patients, who were treated with SES versus RO-ZES. These findings may be considered as a signal of safety and efficacy of the studied DES in patients with diabetes.

Topics: Biodegradable Plastics; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Humans; Multicenter Studies as Topic; Prosthesis Design; Randomized Controlled Trials as Topic; Research Design; Sirolimus

Objective To evaluate the 1-year clinical outcomes of patients who received the Resolute Onyx™ stent. Methods This was a single-centre, retrospective registry analysis that reviewed the clinical data from all patients who were implanted with a Resolute Onyx™ stent between March 2015 and February 2016. Clinical follow-up was performed at 1 year post-implantation. Results A total of 252 patients received a Resolute Onyx™ stent and two patients were lost to follow-up. The mean age of the cohort was 66.9 years and 113 (45.2%) had diabetes mellitus. Thirty-eight patients (15.2%) had left main disease and 73 (29.2%) had three-vessel disease. A total of 175 patients (70.0%) had small vessel disease (<2.75 mm) and 210 (84.0%) had long lesions (>20 mm). The 1-year target lesion failure was 4.4% (11 of 250), cardiovascular death occurred in eight patients (3.2%), ischaemia-driven target lesion revascularization was undertaken in five patients (2.0%) and stent thrombosis occurred in one patient (0.4%). Conclusion The Resolute Onyx™ stent showed a favourable 1-year clinical performance in a real-world population.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Registries; Retrospective Studies; Sirolimus; Survival Analysis; Time Factors; Treatment Outcome

To assess clinical outcomes of Amphilimus Sirolimus-Eluting Stents (A-SES) as compared to Zotarolimus-Eluting Stents (ZES) in complex real-world diabetic patients.. Patients with diabetes mellitus represent one of the most challenging scenarios with high rates of restenosis and stent thrombosis in the current era of drug-eluting stents. Hence, we assessed the safety of A-SES versus ZES in complex diabetic patients.. In this observational study, we analyzed all consecutive patients with diabetes mellitus referred to our center from November 2012 to November 2014. The primary outcome was target-lesion failure at 1-year follow-up.. A total of 165 consecutive diabetic patients underwent percutaneous coronary intervention with A-SES or ZES for stable coronary artery disease in our tertiary center. Using the Kaplan Meier method the cumulative incidence of target-lesion failure was 6.7% (5.9% A-SES versus 7.5% ZES, p=0.19) at 1-year follow-up. Event-free survival at 1year follow-up was similar (89.4% A-SES vs. 83.3% ZES, p=0.29). Interestingly, we did not find any cases of definite-, and only one case of probable stent thrombosis in this high risk cohort.. In this real-world registry, A-SES and ZES seems to be associated with promising 1-year clinical safety outcomes following PCI in a contemporary cohort of high-risk diabetic patients. Our results should be considered hypothesis generating, as the clinical safety of A-SES has to be confirmed in a large trial.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Netherlands; Percutaneous Coronary Intervention; Progression-Free Survival; Prosthesis Design; Registries; Retrospective Studies; Risk Factors; Sirolimus; Time Factors

To date, it remains unknown whether different types of new-generation drug-eluting stents have a differential impact on long-term outcomes in diabetic patients.. In this historical cohort study (two Italian centers), we analyzed 400 diabetic patients with 553 coronary lesions treated with new-generation CoCr zotarolimus-eluting stents (R-ZES: 136 patients, 196 lesions) or everolimus-eluting stents (EES: 264 patients, 357 lesions) between October 2006 and August 2012. Primary endpoint was the occurrence of major adverse cardiac events (MACE) over a 2-year follow-up period. MACE was defined as all-cause mortality, any myocardial infarction (MI) and/or target lesion revascularization (TLR). Multivessel revascularization, intervention for restenotic lesion and use of intravascular ultrasound were significantly higher in the R-ZES group, whereas small stent (≤2.5 mm) deployment was significantly higher in the EES group. At 2-year follow-up, there was no significant difference in occurrence of MACE (R-ZES vs EES: 22.8% vs 18.9%, P = 0.39). Similarly, no significant differences were observed in the composite endpoint of all-cause mortality/MI (10.0% vs 10.3%, P = 0.86) or TLR (12.4% vs 7.4%, P = 0.11). Adjustment for confounders and baseline propensity-score matching did not alter the aforementioned associations.. After 2 years of follow up similar outcomes (MACE, all-cause mortality/MI, TLR) were observed in real-world diabetic patients, including those with complex lesions and patient characteristics, treated with R-ZES and EES.

Topics: Aged; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Japan; Male; Percutaneous Coronary Intervention; Postoperative Complications; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

This study compared safety and efficacy of first- and second-generation DES in an unrestricted, real-life population of diabetic patients undergoing PCI.. The study was a subanalysis of diabetic patients from the all-comer Katowice-Zabrze Registry of patients undergoing PCI with the implantation of either first- (Paclitaxel-, Sirolimus-eluting stents) or second-generation DES (Zotarolimus-, Everolimus-, Biolimus-eluting stents). Efficacy defined as major adverse cardiac and cerebrovascular events (MACCE: death, myocardial infarction, target vessel revascularization, stroke) and safety defined as stent thrombosis (ST) were evaluated at 1 year.. From the total of 1916 patients, 717 were diabetics. Among them, 257 (36%) were treated with first-generation DES (230 [89%] Paclitaxel-eluting stents, 27 [11%] Sirolimus-eluting stents), 460 with second-generation DES (171 [37%] Zotarolimus-eluting stents, 243 [53%] Everolimus-eluting stents, 46 [10%] Biolimus-eluting stents). Rate of MACCE was equal in both groups (p=0.54). Second-generation DES had a better safety profile than first-generation DES (log-rank for cumulative ST at 1 year p<0.001). First-generation DES was a risk factor for ST (HR 5.75 [1.16-28.47], p=0.03) but not for MACCE (HR 0.89 [0.6-1.32], p=0.57).. In a real-life setting of diabetic patients undergoing PCI, second-generation DES had lower risk of ST and similar MACCE rate compared to first-generation DES.

Topics: Aged; Angiography; Coronary Stenosis; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Paclitaxel; Percutaneous Coronary Intervention; Poland; Proportional Hazards Models; Registries; Retrospective Studies; Sirolimus; Stents; Thrombosis; Treatment Outcome

Topics: Cardiovascular Agents; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Female; Humans; Male; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus

To retrospectively evaluate the 12-month effectiveness of the Endeavor zotarolimus-eluting stent (ZES) in diabetic versus non-diabetic patients enrolled in the E-Five Registry.. The E-Five Registry is a prospective, multicentre registry of 8314 patients presenting with symptomatic coronary artery disease treated with the Endeavor (ZES). Patients were treated at 188 centres located in 37 countries across Europe, Latin America and Asia Pacific.. There were 2721 (32.7%) patients with diabetes (DM) and among these patients 682 were insulin-treated (ITDM) and 2039 were non-insulin-treated diabetic patients (NITDM). Interventions All enrolled patients received an Endeavor ZES and were followed for 12 months.. The primary outcome measure was major adverse cardiac event (MACE) at 12 months. Secondary endpoints included target lesion revascularisation (TLR), target vessel revascularisation (TVR), target vessel failure (TVF) and stent thrombosis.. Compared with non-DM patients, DM patients had higher rates of MACE (9.7% vs 6.4%, p<0.001), TLR (5.3% vs 4.0%, p=0.028) and Academic Research Consortium (ARC) definite and probable stent thrombosis (1.5% vs 0.9%, p=0.041). Compared with non-DM patients, ITDM patients had higher rates of MACE (12.6% vs 6.4%, p<0.001). ITDM patients had higher rates of death (6.7% vs 1.7%, p<0.001), cardiac death (4.5% vs 1.2%, p<0.001) and TLR (6.5% vs 4.0%, p=0.011) than non-DM patients.. The Endeavor ZES performed well in DM patients; however, DM patients experienced higher rates of adverse clinical events compared with non-DM patients. TRIAL REG NO:. http://www.clinicaltrials.gov; Unique identifier: NTC00623441.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Epidemiologic Methods; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Registries; Sirolimus; Thrombosis; Treatment Outcome