Paolo Zocca

Thin composite wire strut, durable polymer-coated (Resolute Onyx) versus ultrathin cobalt–chromium strut, bioresorbable polymer-coated (Orsiro) drug-eluting stents in allcomers with coronary artery disease (BIONYX): an international, single-blind, randomised non-inferiority trial

BACKGROUND During the past decade, many patients had zotarolimus-eluting stents implanted, which had circular shape cobalt-chromium struts with limited radiographic visibility. The Resolute Onyx stent was developed to improve visibility while reducing strut thickness, which was achieved by using a novel composite wire with a dense platinum-iridium core and an outer cobalt-chromium layer. We did the first randomised clinical trial to assess the safety and efficacy of this often-used stent compared with the Orsiro stent, which consists of ultrathin cobalt-chromium struts. METHODS We did an investigator-initiated, assessor-blinded and patient-blinded, randomised non-inferiority trial in an allcomers population at seven independently monitored centres in Belgium, Israel, and the Netherlands. Eligible participants were aged 18 years or older and required percutaneous coronary intervention with drug-eluting stents. After guide wire passage with or without predilation, members of the catheterisation laboratory team used web-based computer-generated allocation sequences to randomly assign patients (1:1) to either the Resolute Onyx or the Orsiro stent. Randomisation was stratified by sex and diabetes status. Patients and assessors were masked to allocated stents, but treating clinicians were not. The primary endpoint was target vessel failure at 1 year, a composite of cardiac death, target-vessel-related myocardial infarction, and target vessel revascularisation, and was assessed by intention to treat (non-inferiority margin 2·5%) on the basis of outcomes adjudicated by an independent event committee. This trial is registered with ClinicalTrials.gov, number NCT02508714. FINDINGS Between Oct 7, 2015, and Dec 23, 2016, 2516 patients were enrolled, 2488 of whom were included in the intention-to-treat analysis (28 withdrawals or screening failures). 1243 participants were assigned to the Resolute Onyx group, and 1245 to the Orsiro group. Overall, 1765 (70·9%) participants presented with acute coronary syndromes and 1275 (51·2%) had myocardial infarctions. 1-year follow-up was available for 2478 (99·6%) patients. The primary endpoint was met by 55 (4·5%) patients in the Resolute Onyx group and 58 (4·7%) in the Orsiro group. Non-inferiority of Resolute Onyx to Orsiro was thus established (absolute risk difference -0·2% [95% CI -1·9 to 1·4]; upper limit of the one-sided 95% CI 1·1%; pnon-inferiority=0·0005). Definite or probable stent thrombosis occurred in one (0·1%) participant in the Resolute Onyx group and nine (0·7%) in the Orsiro group (hazard ratio 0·11 [95% CI 0·01-0·87]; p=0·0112). INTERPRETATION The Resolute Onyx stent was non-inferior to Orsiro for a combined safety and efficacy endpoint at 1-year follow-up in allcomers. The low event rate in both groups suggests that both stents are safe, and the very low rate of stent thrombosis in the Resolute Onyx group warrants further clinical investigation. FUNDING Biotronik and Medtronic.

Long‐Term Outcome of Consecutive Patients With Previous Coronary Bypass Surgery, Treated With Newer‐Generation Drug‐Eluting Stents

Background Percutaneous coronary intervention (PCI) in patients with previous coronary artery bypass grafting (CABG) is associated with adverse clinical events. Although newer generation drug‐eluting stents showed favorable short‐term safety profiles, there is a lack of long‐term outcome data. We evaluated the impact of previous CABG on 5‐year clinical outcomes of patients treated with PCI using newer‐generation drug‐eluting stents. Methods and Results In this patient‐level pooled analysis of the prospective TWENTE (The Real‐World Endeavor Resolute versus Xience V Drug‐Eluting Stent Study in Twente) trial and nonenrolled TWENTE registry, we assessed a consecutive series of patients who underwent PCI with newer‐generation drug‐eluting stents for non–ST‐segment–elevation acute coronary syndromes or stable angina. Of all 1709 patients, 202 (11.8%) had a history of CABG. Patients with previous CABG had significantly higher 5‐year rates of cardiac death (10.4% versus 4.3%; P<0.001) and target vessel revascularization (25.0% versus 8.1%; P<0.001). These differences remained statistically significant after adjustment for differences in baseline characteristics. Landmark analysis revealed that from 1‐ to 5‐year follow‐up, the rates of cardiac death (8.1% versus 3.2%; P<0.001) and target vessel revascularization (17.1% versus 5.9%; P<0.001) were significantly higher in patients with previous CABG. Among patients with a history of CABG, PCI of an obstructed vein graft was associated with a higher rate of 5‐year target vessel revascularization (P=0.003). Conclusions At 5‐year follow‐up after PCI with newer‐generation drug‐eluting stents, the risk of cardiac death and target vessel revascularization was significantly higher in patients with previous CABG. The target vessel revascularization rate was highest in patients who underwent PCI of obstructed vein grafts.

Bioresorbable Polymer-Coated Orsiro Versus Durable Polymer-Coated Resolute Onyx Stents (BIONYX) : Rationale and design of the randomized TWENTE IV multicenter trial

Aim The aim was to compare in a noninferiority trial the efficacy and safety of 2 contemporary drug‐eluting stents (DESs): a novel, durable polymer‐coated stent versus an established bioabsorbable polymer‐coated stent. Methods and results The BIONYX trial (ClinicalTrials.gov‐no.NCT02508714) is an investigator‐initiated, prospective, randomized, patient‐ and assessor‐blinded, international, multicenter study in all‐comer patients with all types of clinical syndromes and lesions who require percutaneous coronary interventions with DES. Patients at 7 study sites in the Netherlands, Belgium, and Israel were randomly assigned (1:1, stratified for gender and diabetes mellitus) to treatment with the novel, zotarolimus‐eluting, durable polymer‐coated Resolute Onyx stent that has a radiopaque, thin‐strut, CoreWire stent platform versus the sirolimus‐eluting, bioresorbable polymer‐coated Orsiro stent (reference device) that has a very thin‐strut, cobalt‐chromium stent backbone. The primary end point is the 1‐year incidence of the composite clinical end point target vessel failure consisting of cardiac death, target vessel–related myocardial infarction, or clinically indicated target vessel revascularization. A power calculation, assuming a target vessel failure rate of 6.0% (noninferiority margin 2.5%), revealed that 2,470 study patients would give the study 80% power (&agr; level 5%), allowing for up to 3% loss to follow‐up. The first patient was enrolled on October 7, 2015; on December 23, 2016, the last patient entered the study. Conclusions BIONYX is a large‐scale, prospective, randomized, international, multicenter trial comparing a novel DES with durable coating versus a reference DES with biodegradable coating in all‐comers. The study is the first randomized assessment of the Resolute Onyx stent, which is an often‐used DES outside the United States.

TCT-357 Impact of Gender and Age on 3-Year Clinical Outcome and Chest Pain of Patients With Coronary Artery Disease Treated With Contemporary Drug-Eluting Stents: A Patient-Level Pooled Analysis

BACKGROUND Women report more often chest pain following percutaneous coronary intervention (PCI), yet little is known about the impact of age on these symptoms. We aimed to assess age and gender-related differences in chest pain following PCI with newergeneration drug-eluting stents (DES). METHODS A patient-level pooled analysis of the TWENTE and DUTCH PEERS randomized trials (NCT01066650; NCT01331707) was performed, in which patients were treated with newer generation permanent polymer DES. The primary endpoint of both studies was target vessel failure (TVF); secondary endpoints included MACE (composite of any death, any myocardial infarction (MI), emergent CABG or target lesion revascularization) and POCE (composite of any death, any MI and any revascularization). RESULTS Clinical follow-up was available in 3,188 patients (99.8%). Women had more risk factors including diabetes (24.2% vs. 17.8%, p65 years. Women 65 years, both women and men reported similar levels of chest pain at rest or mild exertion (8.8% and 8.7%, p=0.76); in this subgroup gender did not independently predict chest pain (adjusted OR 1.27 95%-CI:0.8-1.9, p=0.26). Nevertheless, in women and men similar 3-year rates of TVF, MACE, and POCE were found (11.6% vs. 11.3%, p=0.81; 13.6% vs. 12.5%, p=0.43; 18.8% vs. 18.0%, p=0.60, respectively). CONCLUSION While for both genders the incidence of adverse cardiovascular events was low and similar, women