BackgroundDual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking.ObjectivesTo assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation.MethodsOverall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed.ResultsTwo-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase.ConclusionsIn prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions.

AIMS We sought to assess the performance of drug-eluting stents combining an ultrathin cobalt-chromium platform with a biodegradable polymer across categories of increasing SYNTAX score (SS). METHODS AND RESULTS Patients included in the BIOSCIENCE trial and randomly allocated to treatment with biodegradable polymer sirolimus-eluting stents (BP-SES) or durable polymer everolimus-eluting stents (DP-EES) were categorised according to SS tertiles (low <8, medium 8-15, high >15). The primary endpoint, target lesion failure (TLF), was defined as a composite of cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularisation. The patient-oriented endpoint (POCE) included death, myocardial infarction, or any repeat revascularisation. The SS was available in 2,041 out of 2,119 patients (96.3%). At two-year follow-up, patients with an SS >15 experienced higher rates of both TLF and POCE as compared to patients with medium and low SS (14.5% vs. 8.1% and vs. 5.9%, p<0.001; 22.7% vs. 14.9% and vs. 12.4%; p<0.001), respectively. Comparable rates of the composite endpoints were documented for both stent types in each category of SS. CONCLUSIONS Increasing lesion complexity as assessed by SS was associated with higher rates of TLF and POCE in a contemporary PCI population with minimal exclusion criteria. BP-SES and DP-EES showed comparable performance across the entire spectrum of CAD severity.

Drug eluting stents with biodegradable polymer have been developed to address the risk of very late adverse events. COMPARE II is one of the largest randomized studies comparing the biodegradable polymer-coated biolimus-eluting stent (BES; Nobori®) with second-generation durable polymer-coated

Background: To investigate clinical outcomes of percutaneous coronary intervention using a sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES) compared with a permanent polymer everolimus-eluting stent, Xience (PP-EES) in patients with high risk (ST-segment elevation and non-ST-segment elevation myocardial infarction) acute coronary syndromes (ACS) enrolled in the CENTURY II trial.Methods: CENTURY II is a prospective, multicenter, randomized, single blind, controlled trial comparing BP-SES and PP-EES, with primary endpoint of target lesion failure (TLF) at 9 month post-stent implantation. Out of 1123 patients enrolled in CENTURY II trial, 264 high risk ACS patients were included in this subgroup analysis, and the clinical outcomes including target lesion failure (TLF), target vessel failure (TVF), cardiac death, myocardial infarction, and stent thrombosis were evaluated at 24 months.Results: The baseline clinical, angiographic and procedural characteristics were similar between two groups. At 24 months, TLF occurred in 6.3% of patients receiving a BP-SES and 6.5% of patients receiving a PP-EES (P = 0.95); TVF was 6.3% in patients receiving a BP-SES and 9.4% in patients receiving a PP-EES (P = 0.36). There were no significant differences in cardiac death, myocardial infarction and stent thrombosis rate.Conclusions: BP-SES achieved similar safety and efficacy outcomes as PP-EES in this ACS subgroup of CENTURY II study, at 24-month follow-up. This finding is hypothesis-generating and needs to be confirmed in larger trials with longer follow-up. (C) 2016 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license

AIMSOur aim was to compare the safety and efficacy of a novel, ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) with a thin strut, durable polymer everolimus-eluting stent (DP-EES) in a pre-specified subgroup of patients with acute ST-segment elevation myocardial infarction (STEMI) enrolled in the BIOSCIENCE trial.METHODS AND RESULTSThe BIOSCIENCE trial is an investigator-initiated, single-blind, multicentre, randomised non-inferiority trial (NCT01443104). Randomisation was stratified according to the presence or absence of STEMI. The primary endpoint, target lesion failure (TLF), is a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation within 12 months. Between February 2012 and May 2013, 407 STEMI patients were randomly assigned to treatment with BP-SES or DP-EES. At one year, TLF occurred in seven (3.4%) patients treated with BP-SES and 17 (8.8%) patients treated with DP-EES (RR 0.38, 95% CI: 0.16-0.91, p=0.024). Rates of cardiac death were 1.5% in the BP-SES group and 4.7% in the DP-EES group (RR 0.31, 95% CI: 0.08-1.14, p=0.062); rates of target vessel myocardial infarction were 0.5% and 2.6% (RR 0.18, 95% CI: 0.02-1.57, p=0.082), respectively, and rates of clinically indicated target lesion revascularisation were 1.5% in the BP-SES group versus 2.1% in the DP-EES group (RR 0.69, 95% CI: 0.16-3.10, p=0.631). There was no difference in the risk of definite stent thrombosis.CONCLUSIONSIn this pre-specified subgroup analysis, BP-SES was associated with a lower rate of target lesion failure at one year compared to DP-EES in STEMI patients. These findings require confirmation in a dedicated STEMI trial.

BackgroundNo data are available on the long‐term performance of ultrathin strut biodegradable polymer sirolimus‐eluting stents (BP‐SES). We reported 2‐year clinical outcomes of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus‐Eluting Stent Versus Durable Polymer Everolimus‐Eluting Stent for Percutaneous Coronary Revascularisation) trial, which compared BP‐SES with durable‐polymer everolimus‐eluting stents (DP‐EES) in patients undergoing percutaneous coronary intervention. Methods and ResultsA total of 2119 patients with minimal exclusion criteria were assigned to treatment with BP‐SES (n=1063) or DP‐EES (n=1056). Follow‐up at 2 years was available for 2048 patients (97%). The primary end point was target‐lesion failure, a composite of cardiac death, target‐vessel myocardial infarction, or clinically indicated target‐lesion revascularization. At 2 years, target‐lesion failure occurred in 107 patients (10.5%) in the BP‐SES arm and 107 patients (10.4%) in the DP‐EES arm (risk ratio [RR] 1.00, 95% CI 0.77–1.31, P=0.979). There were no significant differences between BP‐SES and DP‐EES with respect to cardiac death (RR 1.01, 95% CI 0.62–1.63, P=0.984), target‐vessel myocardial infarction (RR 0.91, 95% CI 0.60–1.39, P=0.669), target‐lesion revascularization (RR 1.17, 95% CI 0.81–1.71, P=0.403), and definite stent thrombosis (RR 1.38, 95% CI 0.56–3.44, P=0.485). There were 2 cases (0.2%) of definite very late stent thrombosis in the BP‐SES arm and 4 cases (0.4%) in the DP‐EES arm (P=0.423). In the prespecified subgroup of patients with ST‐segment elevation myocardial infarction, BP‐SES was associated with a lower risk of target‐lesion failure compared with DP‐EES (RR 0.48, 95% CI 0.23–0.99, P=0.043, Pinteraction=0.026). ConclusionsComparable safety and efficacy profiles of BP‐SES and DP‐EES were maintained throughout 2 years of follow‐up. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Background— 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. Methods and Results— 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). Conclusions— 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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01443104.

Background Biodegradable polymers for release of antiproliferative drugs from metallic drug-eluting stents aim to improve long-term vascular healing and efficacy. We designed a large scale clinical trial to compare a novel thin strut, cobalt-chromium drug-eluting stent with silicon carbide-coating releasing sirolimus from a biodegradable polymer (O-SES, Orsiro; Biotronik, Bulach, Switzerland) with the durable polymer-based Xience Prime/Xpedition everolimus-eluting stent (EES) (Xience Prime/Xpedition stent, Abbott Vascular, IL) in an all-comers patient population.Design The multicenter BIOSCIENCE trial (NCT01443104) randomly assigned 2,119 patients to treatment with biodegradable polymer sirolimus-eluting stents (SES) or durable polymer EES at 9 sites in Switzerland. Patients with chronic stable coronary artery disease or acute coronary syndromes, including non-ST-elevation and ST-elevation myocardial infarction, were eligible for the trial if they had at least 1 lesion with a diameter stenosis >50% appropriate for coronary stent implantation. The primary end point target lesion failure (TLF) is a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization within 12 months. Assuming a TLF rate of 8% at 12 months in both treatment arms and accepting 3.5% as a margin for noninferiority, inclusion of 2,060 patients would provide more than 80% power to detect noninferiority of the biodegradable polymer SES compared with the durable polymer EES at a 1-sided type I error of 0.05. Clinical follow-up will be continued through 5 years.Conclusion The BIOSCIENCE trial will determine whether the biodegradable polymer SES is noninferior to the durable polymer EES with respect to TLF.

Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent.We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104.Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority &amp;lt;0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014).In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study.Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland.

To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure (HF) and preserved LVEF ( HFpEF). Patients with HFpEF (LVEF 45; n 123) and HF with reduced LVEF (HFrEF; LVEF 45; n 499) with age 60 years, NYHA class II, and elevated NT-proBNP (400 ng/L or 800 ng/L depending on age) were randomized to medical therapy titrated only to reduce symptoms to NYHA II (symptom-guided) or also to reduce NT-proBNP below the inclusion threshold (NT-proBNP-guided) during a 6-month period. Patients were followed for an additional 12 months. Despite similar treatment escalation, NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF. Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF (P 0.02), while survival and HF hospitalization-free survival did not differ. Among HFpEF patients, NT-proBNP reduction and symptom relief were similar in the symptom-guided (n 59) and NT-proBNP-guided (n 64) group despite more aggressive treatment in the NT-proBNP-guided group. In contrast to effects in HFrEF, NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF, with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival, 0.03 for survival, and 0.01 for HF hospitalization-free survival. Outcomes in HFpEF were not better than in HFrEF, and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF. These preliminary findings suggest that, in contrast to HFrEF, NT-proBNP-guided therapy may not be beneficial in HFpEF.

Background In the BAsel Stent Kosten Effektivitats Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal stents (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known.Methods In BASKET-PROVE II, 2,400 patients with de novo lesions in native vessels >= 3 mm in diameter are randomized 1: 1: 1 to receive a conventional DES, a DES with a biodegradable polymer, or a BMS with biocompatible coating. In addition to aspirin, stable patients with BMS will receive prasugrel for 1 month, whereas all others will receive prasugrel for 12 months. The primary end point will be combined cardiac death, nonfatal myocardial infarction, and target vessel revascularization up to 2 years. Secondary end points include stent thrombosis and major bleeding. The primary aim is to test (1) the noninferiority of a biodegradable-polymer DES to a conventional DES and (2) the superiority of both DESs to BMS. A secondary aim is to compare the outcomes with those of BASKET-PROVE regarding the effects of prasugrel-based vs clopidogrel-based antiplatelet therapy.Results By the end of 2010, 878 patients (37% of those planned) were enrolled.Conclusions This study will test the comparative long-term safety and efficacy of newest-generation stents on the background of contemporary antiplatelet therapy in a large all-comer population undergoing large native coronary artery stenting. (Am Heart J 2012;163:136-141.e1.)

Background Acute decompensated heart failure (ADHF) causes a substantial burden for health care systems. Data to rationally define the need for hospitalization or the appropriate length of stay (LOS) is limited. Our aim was to personalize length of stay in patients admitted to hospital for acute decompensated heart failure. Methods Consecutive patients with ADHF presenting to our emergency department were prospectively followed. We daily conducted a multidisciplinary risk assessment and compared proposed with actually observed triage decisions. Results At presentation, all patients required hospitalization. Median LOS was 11 days including 1 day after reaching medical stability. In 42.7% of patients, hospitalization was prolonged after medical stability mainly for nursing and organizational reasons. Within 30 days of enrollment, 7 (9.3%) patients were rehospitalized, 3 of them for persisting or relapsing heart failure. Conclusions There appears to be potential to shorten inhospital stay in patients with ADHF mainly by providing post discharge ambulatory nursing care in order to improve resource utilization and to diminish “hospitalization-associated disability”.