Summary Background Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting ...bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. Findings The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction =0·007), and exerted a significant ischaemic benefit only in this latter group. Interpretation The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. Funding None.
Summary Background Data for the safety and efficacy of new-generation drug-eluting stents at long-term follow-up, and specifically in patients with ST-segment elevation myocardial infarction, are ...scarce. In the EXAMINATION trial, we compared everolimus-eluting stents (EES) with bare-metal stents (BMS) in an all-comer population with ST-segment elevation myocardial infarction. In this study, we assessed the 5-year outcomes of the population in the EXAMINATION trial. Methods In the multicentre EXAMINATION trial, done in Italy, Spain, and the Netherlands, patients with ST-segment elevation myocardial infarction were randomly assigned in a 1:1 ratio to receive EES or BMS. The random allocation schedule was computer-generated and central randomisation (by telephone) was used to allocate patients in blocks of four or six, stratified by centre. Patients were masked to treatment assignment. At 5 years, we assessed the combined patient-oriented outcome of all-cause death, any myocardial infarction, or any revascularisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00828087. Findings 1498 patients were randomly assigned to receive either EES (n=751) or BMS (n=747). At 5 years, complete clinical follow-up data were obtained for 731 patients treated with EES and 727 treated with BMS (97% of both groups). The patient-oriented endpoint occurred in 159 (21%) patients in the EES group versus 192 (26%) in the BMS group (hazard ratio 0·80, 95% CI 0·65–0·98; p=0·033). This difference was mainly driven by a reduced rate of all-cause mortality (65 9% vs 88 12%; 0·72, 0·52–0·10; p=0·047). Interpretation Our findings should be taken as a point of reference for the assessment of new bioresorbable polymer-based metallic stents or bioresorbable scaffolds in patients with ST-segment elevation myocardial infarction. Funding Spanish Heart Foundation.
Summary Background It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. Methods We did a ...randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov , number NCT01433627. Findings We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio RR 0·85, 95% CI 0·74–0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73–0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49–0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53–0·99; p=0·045). Interpretation In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. Funding The Medicines Company and Terumo.
Summary Background REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal ...oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. Methods We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13 200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus >99% factor IXa inhibition followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov , identifier NCT01848106 . The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. Findings 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio OR 1·05, 95% CI 0·80–1·39; p=0·72). Major bleeding was similar between treatment groups (seven <1% of 1605 receiving REG1 vs two <1% of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73–16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 6% vs 65 4%; 1·64, 1·19–2·25; p=0·002). Interpretation The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. Funding Regado Biosciences Inc.
Summary Background The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were ...powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. Methods We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. Findings Of 43 904 patients recruited in 26 trials of DES, 11 557 (26·3%) were women (mean age 67·1 years SD 10·6). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 18·6% women in the bare-metal stent group, 294 7·8% in the early-generation DES group, and 330 6·3% in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. Interpretation The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. Funding Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.
Summary Background Everolimus-eluting stent (EES) reduces the risk of restenosis in elective percutaneous coronary intervention. However, the use of drug-eluting stent in patients with ST-segment ...elevation myocardial infarction (STEMI) is still controversial. Data regarding the performance of second-generation EES in this setting are scarce. We report the 1-year result of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) trial, comparing EES with bare-metal stents (BMS) in patients with STEMI. Methods This multicentre, prospective, randomised, all-comer controlled trial was done in 12 medical centres in three countries. Between Dec 31, 2008, and May 15, 2010, we recruited patients with STEMI up to 48 h after the onset of symptoms requiring emergent percutaneous coronary intervention. Patients were randomly assigned (ratio 1:1) to receive EES or BMS. Randomisation was in blocks of four or six patients, stratified by centre and centralised by telephone. Patients were masked to treatment. The primary endpoint was the patient-oriented combined endpoint of all-cause death, any recurrent myocardial infarction, and any revascularisation at 1 year and was analysed by intention to treat. The secondary endpoints of the study included the device-oriented combined endpoint of cardiac death, target vessel myocardial infarction or target lesion revascularisation, and rates of all cause or cardiac death, recurrent myocardial infarction, target lesion or target vessel revascularisation, stent thrombosis, device and procedure success, and major and minor bleeding. This trial is registered with ClinicalTrials.gov , number NCT00828087. Findings Of the 1504 patients randomised, 1498 patients were randomly assigned to receive EES (n=751) or BMS (n=747). The primary endpoint was similar in both groups (89 11·9% of 751 patients in the EES group vs 106 14·2% of 747 patients in the BMS group; difference −2·34 95% CI −5·75 to 1·07; p=0·19). Device-oriented endpoint (44 5·9% in the EES group vs 63 8·4% in the BMS group; difference −2·57 95% CI −5·18 to 0·03; p=0·05) did not differ between groups, although rates of target lesion and vessel revascularisation were significantly lower in the EES group (16 2·1% vs 37 5·0%, p=0·003, and 28 3·7% vs 51 6·8%, p=0·0077, respectively). Rates of all cause (26 3·5% for EES vs 26 3·5% for BMS, p=1·00) or cardiac death (24 3·2% for EES vs 21 2·8% for BMS, p=0·76) or myocardial infarction (10 1·3% vs 15 2·0%, p=0·32) did not differ between groups. Stent thrombosis rates were significantly lower in the EES group (4 0·5% patients with definite stent thrombosis in the EES group vs 14 1·9% in the BMS group and seven 0·9% patients with definite or probable stent thrombosis in the EES group vs 19 2·5% in the BMS group, both p=0·019). Although device success rate was similar between groups, procedure success rate was significantly higher in the EES group (731 97·5% vs 705 94·6%; p=0·0050). Finally, Bleeding rates at 1 year were comparable between groups (29 3·9% patients in the EES group vs 39 5·2% in the BMS group; p=0·19). Interpretation The use of EES compared with BMS in the setting of STEMI did not lower the patient-oriented endpoint. However, at the stent level both rates of target lesion revascularisation and stent thrombosis were reduced in recipients of EES. Funding Spanish Heart Foundation.
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