Long-term follow-up of contemporary drug-eluting stent implantation in diabetic patients: Subanalysis of a randomized controlled trial.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Clinical outcomes after permanent polymer or polymer-free stent implantation in patients with diabetes mellitus: The ReCre8 diabetes substudy.

OBJECTIVES: The purpose of this analysis was to compare target-lesion failure (TLF) of a permanent polymer zotarolimus-eluting stent (PP-ZES) versus a polymer-free amphilimus-eluting stent (PF-AES) in diabetics. BACKGROUND: The improvement of outcomes with new-generation drug-eluting stent as seen in the general population is less pronounced among diabetics. The PF-AES introduces an elution-technology with potential enhanced performance in diabetics. METHODS: In this subanalysis of the ReCre8 trial, patients were randomized to either a PP-ZES or PF-AES after stratification for diabetes and troponin status. The primary device-oriented endpoint was TLF, a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. RESULTS: In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin-dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP-ZES 7.2% vs. PF-AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP-ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP-ZES arm and 1 case in the PF-AES arm (p = .32). Regarding insulin-treated diabetics, TLF was higher in the PP-ZES arm (14.9 vs. 2.1%; p = .022). CONCLUSIONS: Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus-formulation). Future trials should confirm the potential benefit of a PF-AES in this population.

High bleeding risk in patients undergoing percutaneous coronary intervention with drug-eluting stent implantation: ReCre8 subanalysis.

Objectives: In an all-comers cohort undergoing percutaneous coronary intervention (PCI), we aimed to assess prevalence of high bleeding risk (HBR) patients and impact of HBR and dual antiplatelet therapy (DAPT) on clinical events. Background: HBR represents a complex subgroup of patients undergoing PCI. Methods: In the ReCre8 trial, patients undergoing PCI were stratified for troponin status and diabetes and randomized to a permanent polymer zotarolimus-eluting- or polymer-free amphilimus-eluting stent. Patients were treated with 12 months (troponin-positive) or one month (troponin-negative) of DAPT. We evaluated clinical outcomes in patients with and without HBR according to the Academic Research Consortium for High Bleeding Risk criteria. Results: From a total of 1488 patients included in this subanalysis, 406 patients (27.3 %) were identified as being at HBR. Among HBR patients, target-lesion failure (TLF) was similar after one year yet was higher after three years (13.3 % vs. 9.1 %; p = 0.013), compared to non-HBR patients. There was no difference in Bleeding Academic Research Consortium (BARC) 3 to 5 bleeding, however BARC 2 to 5 bleeding was higher after three years with 4.9 % vs. 3.0 % (p = 0.037). There were no differences between troponin-positive (12-months DAPT) and -negative (1-month DAPT) HBR patients with respect to ischemic and bleeding outcomes. Conclusions: In this all-comers population of PCI patients, a higher TLF rate among HBR patients at long-term follow-up was found, underlining the complexities involving treatment of HBR patients. We did not observe statistically significant differences in BARC 3 to 5 bleeding between HBR and non-HBR patients regardless of DAPT duration. Clinical trial registration: URL: http://www.clinicaltrials.gov, unique identifier: NCT02328898.

3-Year Clinical Outcomes After Implantation of Permanent-Polymer Versus Polymer-Free Stent: ReCre8 Landmark Analysis.

OBJECTIVES: The aim of this analysis was to assess long-term clinical outcomes of the polymer-free Amphilimus-eluting stent (PF-AES) compared with a latest generation permanent-polymer drug-eluting stent (DES) in an all-comers population. BACKGROUND: PF-AES possess multiple properties improving targeted drug elution without the presence of polymers. Evaluation of long-term clinical performance of PF-AES versus latest generation permanent-polymer DES has not yet been performed in a large randomized trial introducing shortened dual-antiplatelet therapy. METHODS: In this physician-initiated, multicenter, randomized, all-comers trial, patients undergoing percutaneous coronary intervention with implantation of DES were enrolled. Patients were stratified for diabetes and troponin status and randomized to implantation of a permanent-polymer zotarolimus-eluting stent (PP-ZES) or a PF-AES. Dual-antiplatelet therapy duration was 12 months in troponin-positive patients and 1 month in troponin-negative patients. A noninferiority analysis was conducted to compare the 2 arms regarding target lesion failure (TLF) between 1 and 3 years. RESULTS: A total of 1,491 patients were randomized and treated. In this landmark analysis, between 1- and 3-year follow-up, TLF occurred in 35 patients (4.9%) in the PP-ZES arm and 37 PF-AES patients (5.1%). Clinical noninferiority of the PF-AES was confirmed, with a risk difference of 0.2% (upper limit 1-sided 95% CI: 2.2%; Pnoninferiority = 0.0031). CONCLUSIONS: ReCre8 (Randomized "All-Comer" Evaluation of a Permanent Polymer Resolute Integrity Stent Versus a Polymer Free Cre8 Stent) is the first randomized, multicenter trial with a head-to-head comparison of PP-ZES compared with PF-AES to investigate clinical outcomes of these new-generation DES in an all-comers population with long-term follow-up. On the basis of the present results, PF-AES are clinically noninferior to PP-ZES regarding TLF between 1 and 3 years. (Randomized "All-Comer" Evaluation of a Permanent Polymer Resolute Integrity Stent Versus a Polymer Free Cre8 Stent; NCT02328898).

Patient-tailored antithrombotic therapy following percutaneous coronary intervention.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.

One-year clinical outcomes of patients treated with polymer-free amphilimus-eluting stents or zotarolimus-eluting stents: A propensity-score adjusted analysis.

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution-technology in coronary stenting. We aimed to assess 1-year clinical outcomes of PF-AES as compared to latest-generation permanent polymer zotarolimus-eluting stents (PP-ZES) in a real-world all-comers setting. METHODS: A prospective registry of patients treated with either PF-AES or PP-ZES between 2014 and 2016 was conducted. The primary outcome was defined as major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcome was defined as target-lesion failure (TLF) at 1 year. To account for measured confounders, a propensity-score adjusted Cox proportional-hazard model was built to evaluate clinical outcomes. RESULTS: A total of 734 consecutive patients with 1,269 DES implantations were enrolled. The population was characterized by 28% diabetes, 24% ST-segment elevation myocardial infarction, and a high number of complex lesions (69%). The rate of MACCE was 11.5% for PF-AES and 13.6% for PP-ZES, plog-rank = 0.11. TLF was numerically lower in PF-AES as compared to PP-ZES (5.4 vs. 6.1%, plog-rank = 0.68). After propensity-score adjustment, PF-AES showed a trend toward a lower rate of MACCE and a favorable rate of TLF as compared to PP-ZES (HR 0.70; 95%CI 0.45 to 1.10, P = 0.12; and HR 0.88; 95%CI 0.47 to 1.65, P = 0.68, respectively). Rates of definite ST were low (0.8 vs. 0.3%, plog-rank = 0.62). CONCLUSIONS: Our study suggests that implantation of PF-AES was safe and effective in real-world patients, with low-rates of MACCE and TLF at 1 year. Our data needs to be confirmed by a large trial to evaluate the clinical outcomes of this novel polymer-free, eluting-technology used in PF-AES.

Randomized All-Comers Evaluation of a Permanent Polymer Zotarolimus-Eluting Stent Versus a Polymer-Free Amphilimus-Eluting Stent.

BACKGROUND: Polymer-free amphilimus-eluting stents (PF-AES) represent a novel elution technology in the current era of drug-eluting stents. The clinical safety and efficacy of PF-AES as compared with latest-generation permanent-polymer zotarolimus-eluting stents (PP-ZES) have not yet been investigated in a large randomized trial. METHODS: In this physician-initiated, prospective, multicenter, randomized, noninferiority trial, an all-comers population requiring percutaneous coronary intervention was enrolled across 3 European sites. Randomization (1:1 ratio) to PP-ZES or PF-AES was performed after stratification for troponin status and diabetes mellitus. In both treatment arms, troponin-positive patients were planned for 12-month dual antiplatelet therapy, whereas troponin-negative patients were planned for 1-month dual antiplatelet therapy. Outcome assessors were blinded to the allocated treatment. The device-oriented primary end point of target-lesion failure was defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization at 12-months as analyzed by modified intention-to-treat (80% power, and a 3.5% noninferiority margin). RESULTS: In total, 1502 patients were randomized and 1491 treated with the assigned stent and available for follow-up. The primary end point occurred in 42 (5.6%) of the 744 patients receiving PP-ZES versus 46 (6.2%) of the 747 patients receiving PF-AES. PF-AES were clinically noninferior to PP-ZES (risk difference, 0.5%; upper limit 1-sided 95% confidence interval, 2.6%; Pnoninferiority=0.0086). Cardiac death occurred in 10 (1.3%) versus 10 patients (1.3%; P value for difference, 1.00), target-vessel myocardial infarction occurred in 18 (2.4%) versus 17 patients (2.3%; P value for difference, 0.87), and target-lesion revascularization occurred in 22 (2.9%) versus 20 patients (2.6%; P value for difference, 0.75) for PF-AES as compared with PP-ZES. Overall, definite or probable stent thrombosis occurred in 1.0%. CONCLUSIONS: PF-AES were noninferior to PP-ZES regarding target-lesion failure at 12 months. Findings regarding the secondary end point and prespecified subgroups were generally consistent with that of the primary end point. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02328898.

Rationale and design of amphilimus sirolimus-eluting stents versus zotarolimus-eluting stents in all-comers requiring percutaneous coronary intervention (ReCre8): A multicenter randomized clinical trial.

BACKGROUND: Amphilimus sirolimus-eluting stents (A-SES) represent a novel elution technology in the current era of drug-eluting stents with promising results in patients with diabetes mellitus. At present no large trial has been designed to evaluate clinical outcomes of A-SES as compared to new-generation drug-eluting stents in unselected patients. Accordingly, we designed this trial to evaluate clinical noninferiority of A-SES as compared with zotarolimus-eluting stents (ZES) in a real-world, all-comers setting. STUDY DESIGN: ReCre8 is a prospective multicenter randomized clinical trial evaluating the clinical outcomes of A-SES as compared with ZES in all-comers requiring percutaneous coronary intervention. Patients are randomized 1:1 to receive either A-SES or ZES. On-site block-randomization is stratified by diabetes mellitus, and troponin status to perform prespecified subanalyses. Patients receive 1-month of dual antiplatelet therapy (DAPT) when troponin-negative, or 12-months of DAPT when troponin-positive. The primary endpoint is target-lesion failure at 1-year follow-up. A total of 1,532 patients will be enrolled to demonstrate clinical noninferiority of A-SES with at least 80% power, a noninferiority margin of 3.5% and a type-I-error of 0.05. CONCLUSIONS: ReCre8 (NCT02328898) is the first randomized multicenter trial with a head-to-head comparison of A-SES as compared with ZES to investigate the clinical safety and efficacy of these new-generation DES in a real-world, all-comers population.

Clinical outcomes of complex real-world diabetic patients treated with amphilimus sirolimus-eluting stents or zotarolimus-eluting stents: A single-center registry.

OBJECTIVE: To assess clinical outcomes of Amphilimus Sirolimus-Eluting Stents (A-SES) as compared to Zotarolimus-Eluting Stents (ZES) in complex real-world diabetic patients. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.