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Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi‐database cohort study with meta‐analysis
Author(s) -
Durand Madeleine,
Schnitzer Mireille E.,
Pang Menglan,
Carney Greg,
Eltonsy Sherif,
Filion Kristian B.,
Fisher Anat,
Jun Min,
Kuo I. Fan,
Matteau Alexis,
Paterson J. Michael,
Quail Jacqueline,
Renoux Christel
Publication year - 2021
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14669
Subject(s) - apixaban , rivaroxaban , dabigatran , medicine , atrial fibrillation , stroke (engine) , hazard ratio , warfarin , proportional hazards model , confidence interval , mechanical engineering , engineering
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.