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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Journal articlePermalink
https://hdl.handle.net/10161/15450Published Version (Please cite this version)
10.1016/S0140-6736(17)30751-1Publication Info
Ohman, E Magnus; Roe, Matthew T; Steg, P Gabriel; James, Stefan K; Povsic, Thomas
J; White, Jennifer; ... Gibson, C Michael (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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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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 ad
Thomas Joseph Povsic
Professor of Medicine
Frank Wesley Rockhold
Professor of Biostatistics & Bioinformatics
Frank is a full time Professor of Biostatistics and Bioinformatics and Faculty Director
for Biostatistics at Duke University Medical Center, Affiliate Professor of Biostatistics
at Virginia Commonwealth University, and Strategic Consultant at Hunter Rockhold,
Inc. His 40+-year career includes senior research positions at Lilly, Merck, and
GlaxoSmithKline, where he retired as Chief Safety Officer and Senior Vice President
of Global Clinical Safety and Pharmacovigilance. He h
Matthew Todd Roe
Adjunct Professor in the Department of Medicine
My clinical activities focus upon general, preventive, and acute care cardiology.
I round regularly on the inpatient general cardiology and coronary care unit (CCU)
services and i have a particular interest in the treatment and management of patients
with acute myocardial infarction and cardiogenic shock. In my outpatient clinic,
I care for patients with a variety of cardiovascular conditions include chronic coronary
artery disease, hypertension, hyperlipidemia, atrial fibrillation,
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