Direct Comparison of Dabigatran, Rivaroxaban, and Apixaban for Effectiveness and Safety in Nonvalvular Atrial Fibrillation

Chest. 2016 Dec;150(6):1302-1312. doi: 10.1016/j.chest.2016.07.013. Epub 2016 Sep 28.


Background: The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation (AF). Patients and clinicians now have a choice between different NOACs, but there is no direct comparative effectiveness evidence to guide decision-making. We aimed to compare the effectiveness and safety of dabigatran, rivaroxaban, and apixaban in clinical practice.

Methods: Using a large US administrative claims database, we created three one-to-one propensity-score-matched cohorts of patients with nonvalvular AF who were users of dabigatran, rivaroxaban, or apixaban between October 1, 2010 and February 28, 2015 (rivaroxaban vs dabigatran, n = 31,574; apixaban vs dabigatran, n = 13,084; and apixaban vs rivaroxaban, n = 13,130). The primary outcomes were stroke and systemic embolism (effectiveness) and major bleeding (safety) that occurred during treatment. Cox proportional hazards models were used to compare outcomes in propensity-score-matched cohorts.

Results: We found no differences between the three NOACs in the risk of stroke or systemic embolism (hazard ratio [HR], 1.00; 95% CI, 0.75-1.32 for rivaroxaban vs dabigatran; HR, 0.82; 95% CI, 0.51-1.31 for apixaban vs dabigatran; and HR, 1.05; 95% CI, 0.64-1.72 for apixaban vs rivaroxaban). Apixaban was associated with a lower risk of major bleeding (HR, 0.50; 95% CI, 0.36-0.70; P < .001 vs dabigatran and HR, 0.39; 95% CI, 0.28-0.54; P < .001 vs rivaroxaban). Rivaroxaban was associated with an increased risk of major bleeding (HR, 1.30; 95% CI, 1.10-1.53; P < .01) and intracranial bleeding (HR, 1.79; 95% CI, 1.12-2.86; P < .05) compared with dabigatran.

Conclusions: Dabigatran, rivaroxaban, and apixaban appear to have similar effectiveness, although apixaban may be associated with a lower bleeding risk and rivaroxaban may be associated with an elevated bleeding risk.

Keywords: atrial fibrillation; bleeding; non-vitamin K antagonist oral anticoagulants; stroke.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antithrombins / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Cerebral Hemorrhage / chemically induced
  • Dabigatran / therapeutic use*
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Propensity Score
  • Pyrazoles / therapeutic use*
  • Pyridones / therapeutic use*
  • Retrospective Studies
  • Rivaroxaban / therapeutic use*
  • Stroke / prevention & control*
  • United States


  • Antithrombins
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
  • Dabigatran