Madeleine Durand1, Mireille E Schnitzer2,3,4, Menglan Pang4, Greg Carney5, Sherif Eltonsy6, Kristian B Filion4,7,8, Anat Fisher, Min Jun9, I Fan Kuo10, Alexis Matteau5,11, J Michael Paterson12, Jacqueline Quail13,14, Christel Renoux4,7,15. 1. Internal Medicine service, Centre Hospitalier de l'Université de Montréal (CHUM) and CHUM Research Center, Montreal, QC, Canada. 2. Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada. 3. Department of Social and Preventive Medicine, Université de Montréal, Montreal, QC, Canada. 4. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. 5. Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. 6. College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Canada. 7. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada. 8. Department of Medicine, McGill University, Montreal, QC, Canada. 9. The George Institute for Global Health, University of New South Wales, Sydney, Australia. 10. College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. 11. Cardiology service, Centre Hospitalier de l'Université de Montréal (CHUM) and CHUM Research Center, Montreal, QC, Canada. 12. ICES, Toronto, ON, Canada (JMP). Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. 13. Health Quality Council, Saskatoon, SK, Canada. 14. Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, SK, Canada. 15. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Abstract
AIMS: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). METHODS: We conducted multicentre matched cohort studies with secondary meta-analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across 9 administrative healthcare databases. We included adults with NVAF initiating anticoagulation therapy (dabigatran, rivaroxaban or apixaban), and constructed 3 cohorts to compare DOACs pairwise. The primary outcome was pooled hazard ratio (pHR) of ischaemic stroke or systemic thromboembolism. Secondary outcomes included pHR of major bleeding, and a composite of stroke, major bleeding, or all-cause mortality. We used proportional hazard Cox regressions models, and pooled estimates were obtained with random effect meta-analyses. RESULTS: The cohorts included 73 414 new users of dabigatran, 92 881 of rivaroxaban, and 61 284 of apixaban. After matching, the pHRs (95% confidence intervals) comparing rivaroxaban initiation to dabigatran were: 1.11 (0.93, 1.32) for ischaemic stroke or systemic thromboembolism, 1.26 (1.09, 1.46) for major bleeding, and 1.17 (1.05, 1.30) for the composite endpoint. For apixaban vs dabigatran, they were: 0.91 (0.74, 1.12) for ischaemic stroke or systemic thromboembolism, 0.89 (0.75, 1.05) for major bleeding, and 0.94 (0.78 to 1.14) for the composite endpoint. For apixaban vs rivaroxaban, they were: 0.85 (0.74, 0.99) for ischaemic stroke or systemic thromboembolism, 0.61 (0.53, 0.70) for major bleeding, and 0.82 (0.76, 0.88) for the composite endpoint. CONCLUSION: We found that apixaban use is associated with lower risks of stroke and bleeding compared with rivaroxaban, and similar risks compared with dabigatran.
AIMS: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). METHODS: We conducted multicentre matched cohort studies with secondary meta-analysis to assess safety and effectiveness of dabigatran, rivaroxaban and apixaban across 9 administrative healthcare databases. We included adults with NVAF initiating anticoagulation therapy (dabigatran, rivaroxaban or apixaban), and constructed 3 cohorts to compare DOACs pairwise. The primary outcome was pooled hazard ratio (pHR) of ischaemic stroke or systemic thromboembolism. Secondary outcomes included pHR of major bleeding, and a composite of stroke, major bleeding, or all-cause mortality. We used proportional hazard Cox regressions models, and pooled estimates were obtained with random effect meta-analyses. RESULTS: The cohorts included 73 414 new users of dabigatran, 92 881 of rivaroxaban, and 61 284 of apixaban. After matching, the pHRs (95% confidence intervals) comparing rivaroxaban initiation to dabigatran were: 1.11 (0.93, 1.32) for ischaemic stroke or systemic thromboembolism, 1.26 (1.09, 1.46) for major bleeding, and 1.17 (1.05, 1.30) for the composite endpoint. For apixaban vs dabigatran, they were: 0.91 (0.74, 1.12) for ischaemic stroke or systemic thromboembolism, 0.89 (0.75, 1.05) for major bleeding, and 0.94 (0.78 to 1.14) for the composite endpoint. For apixaban vs rivaroxaban, they were: 0.85 (0.74, 0.99) for ischaemic stroke or systemic thromboembolism, 0.61 (0.53, 0.70) for major bleeding, and 0.82 (0.76, 0.88) for the composite endpoint. CONCLUSION: We found that apixaban use is associated with lower risks of stroke and bleeding compared with rivaroxaban, and similar risks compared with dabigatran.
Authors: Benjamin J R Buckley; Deirdre A Lane; Peter Calvert; Juqian Zhang; David Gent; C Daniel Mullins; Paul Dorian; Shun Kohsaka; Stefan H Hohnloser; Gregory Y H Lip Journal: J Clin Med Date: 2022-06-30 Impact factor: 4.964
Authors: Sylvie Perreault; Alice Dragomir; Robert Côté; Aurélie Lenglet; Simon de Denus; Marc Dorais; Brian White-Guay; James Brophy; Mireille E Schnitzer; Marie-Pierre Dubé; Jean-Claude Tardif Journal: Front Pharmacol Date: 2022-01-14 Impact factor: 5.810