Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.

Abstract

BACKGROUND: Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months. METHODS: In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1:1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2·5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395. FINDINGS: Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1·09 [95% CI 0·80-1·50]; p=0·5840). INTERPRETATION: A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach. FUNDING: Janssen Research & Development and Bayer AG.

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10.1016/S0140-6736(17)30751-1

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Ohman, E Magnus, Matthew T Roe, P Gabriel Steg, Stefan K James, Thomas J Povsic, Jennifer White, Frank Rockhold, Alexei Plotnikov, et al. (2017). Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet, 389(10081). pp. 1799–1808. 10.1016/S0140-6736(17)30751-1 Retrieved from https://hdl.handle.net/10161/15450.

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Ohman

Erik Magnus Ohman

Professor of Medicine

Dr. Ohman, Professor of Medicine, received medical degrees from the Royal College of Surgeons in Ireland and the National University of Ireland (1984, Fellowship 1984-1987), and completed his training in cardiology at Duke University (1987-1991), where he has remained on faculty. In 2001, he became Chief of Cardiology at the University of North Carolina at Chapel Hill, where he founded the UNC Heart Center and became its first director. In 2005 he returned to Duke to pursue his interest in advanced coronary disease as the Director of the Program for Advanced Coronary Disease. Since that time, he has been appointed to Associate Director of the Duke Heart Center, the Kent and Siri Rawson Director for the Program for Advanced Coronary Disease, and most recently, Vice-Chair of Development and Innovation in the Department of Medicine.

Dr. Ohman’s clinical and research interests include interventional cardiology and high-risk supported PCI, and treatment of patients with advanced/complex coronary disease. He has researched how to improve patient care through the use of guidelines-based therapies and adherence, and examining global cardiovascular risk and health. He has been a participant on numerous guidelines writing committees, served on the ACC/AHA oversight committee for guidelines development, and has served on the steering committees for trials on ST-elevation myocardial infarction and non-ST-elevation ACS. He is a consultant to the National Institutes of Health, and a consultant for the FDA Advisory Panel for Cardiovascular Devices. 

Dr. Ohman has published over 600 peer-reviewed papers and three books in cardiovascular medicine. He holds three U.S. patents in reperfusion therapy. He is an associate editor for the American Heart Journal and serves on the editorial boards of the Journal of the American College of Cardiology and the American Journal of Cardiology.  He is a Fellow of the Royal College of Physicians in Ireland, the Royal Society of Medicine (U.K.), the European Society of Cardiology, the Society of Cardiac Angiography and Interventions, and the American College of Cardiology. 


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