• Madeleine Durand, Mireille E Schnitzer, Menglan Pang, Greg Carney, Sherif Eltonsy, Kristian B Filion, Anat Fisher, Min Jun, I Fan Kuo, Christel Renoux, J Michael Paterson, Jacqueline Quail, Alexis Matteau, and Canadian Network for Observational Drug Effect Studies Investigators.
• Internal Medicine Service (Durand), Centre hospitalier de l'Université de Montréal (CHUM) and CHUM Research Centre (Durand); Faculty of Pharmacy (Schnitzer) and Department of Social and Preventive Medicine (Schnitzer), Université de Montréal; Departments of Epidemiology, Biostatistics and Occupational Health (Schnitzer, Pang, Filion, Renoux), Medicine (Filion) and Neurology and Neurosurgery (Renoux), McGill University, Montréal, Que.; Departments of Anesthesiology, Pharmacology and Therapeutics (Carney, Fisher), Faculty of Medicine, University of British Columbia, Vancouver, BC; College of Pharmacy (Eltonsy, Kuo), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Clinical Epidemiology (Filion, Renoux), Lady Davis Institute, Jewish General Hospital, Montréal, Que.; The George Institute for Global Health (Jun), University of New South Wales, Sydney, Australia; ICES Central (Paterson); Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Health Quality Council (Quail) and Department of Community Health and Epidemiology (Quail), University of Saskatchewan, Saskatoon, Sask.; Cardiology Service (Matteau), CHUM and CHUM Research Centre, Montréal, Que. madeleine.durand.chum@ssss.gouv.qc.ca.
• CMAJ Open. 2020 Oct 1; 8 (4): E877-E886.

BackgroundDirect oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.MethodsWe conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009-2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses.ResultsWe included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85).InterpretationIn this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation.Trial RegistrationClinicalTrials.gov, no. NCT03596502.Copyright 2020, Joule Inc. or its licensors.

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