30 Nov 2020 Effectiveness and Safety among Direct Oral Anticoagulants in Non Valvular Atrial Fibrillation: A Multi‐Database Cohort Study with Meta‐Analysis
British Journal of Clinical Pharmacology, November 2020
Madeleine Durand, Mireille E. Schnitzer, Menglan Pang, Greg Carney, Sherif Eltonsy, Kristian B. Filion, Anat Fisher, Min Jun, I. fan Kuo, Alexis Matteau, J. Michael Paterson, Jacqueline Quail, Christel Renoux for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators
Abstract
Background: There are conflicting signals in the literature about comparative safety and effectiveness of direct oral anticoagulants (DOACs) for non‐valvular atrial fibrillation (NVAF).
Methods: We conducted multi‐center 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 ischemic 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 ischemic 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 ischemic 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 ischemic 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.
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