Effectiveness and safety among direct oral anticoagulants in nonvalvular atrial fibrillation: A multi-database cohort study with meta-analysis

Br J Clin Pharmacol. 2021 Jun;87(6):2589-2601. doi: 10.1111/bcp.14669. Epub 2020 Dec 16.

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.

Keywords: atrial fibrillation; direct oral anticoagulants; epidemiology; stroke.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Brain Ischemia* / drug therapy
  • Cohort Studies
  • Dabigatran / adverse effects
  • Humans
  • Pyridones / adverse effects
  • Retrospective Studies
  • Rivaroxaban / adverse effects
  • Stroke* / drug therapy
  • Stroke* / epidemiology
  • Stroke* / prevention & control
  • Treatment Outcome
  • Warfarin

Substances

  • Anticoagulants
  • Pyridones
  • Warfarin
  • Rivaroxaban
  • Dabigatran