Related Experiment Video
Updated: Aug 23, 2025
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With
Wallis C Y Lau1, Carmen Olga Torre2, Kenneth K C Man1
1Research Department of Practice and Policy, University College London School of Pharmacy, London, United Kingdom, Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom, Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, and Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong (W.C.Y.L., K.K.C.M.).
Background:
Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC.
Objective:
To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice.
Design:
Multinational population-based cohort study.
Setting:
Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States.
Participants:
Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription.
Measurements:
Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model.
Results:
A total of 527 226 new DOAC users met the inclusion criteria (apixaban, n = 281 320; dabigatran, n = 61 008; edoxaban, n = 12 722; and rivaroxaban, n = 172 176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95% CI, 0.70 to 0.94]), edoxaban (HR, 0.77 [CI, 0.66 to 0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66 to 0.79]). No substantial differences were observed for other outcomes or DOAC-DOAC comparisons. The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 [CI, 0.64 to 0.82]), those receiving a reduced dose (HR, 0.68 [CI, 0.61 to 0.77]), and those with chronic kidney disease (HR, 0.68 [CI, 0.59 to 0.77]).
Limitation:
Residual confounding is possible.
Conclusion:
Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials.
Primary Funding Source:
None.
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