Comparison of the effectiveness and safety of direct oral anticoagulants: nationwide propensity score-weighted study

In the pivotal randomized controlled trials (RCTs) for patients with atrial fibrillation, direct oral anticoagulants (DOACs) had similar or even superior efficacy and safety compared to warfarin. However, RCTs comparing different DOACs are non-existent and previous observational studies have yielded conflicting results. In this nationwide cohort study, rates of any stroke or systemic embolism (stroke/SE) and major bleeding were compared between new users of apixaban, dabigatran, and rivaroxaban with atrial fibrillation from 2014-2019. Inverse probability weighting was used to yield balanced study groups and outcomes were compared using Cox regression. Stroke/SE rates were similar between patients receiving apixaban, dabigatran, and rivaroxaban. Dabigatran was associated with twofold higher rates of myocardial infarction compared to rivaroxaban (1.4 events/100-py vs 0.7 events/100-py, HR 2.21, 95% CI 1.00-4.90) and apixaban (1.4 events/100-py vs 0.7 events/100-py, HR 2.26, 95% CI 0.90-5.67), although the second comparison included the possibility of a null effect. Rivaroxaban was associated with higher major bleeding rates compared to apixaban (2.9 events/100-py vs 1.8 events/100-py, HR 1.64, 95% CI 1.13-2.37) and dabigatran (2.9 events/100-py vs 1.4 events/100-py, HR 2.18, 95% CI 1.21-3.93). Specifically, rivaroxaban had higher rates of major gastrointestinal bleeding and other major bleeding compared to apixaban. In conclusion, while stroke/SE rates were similar between DOACs, rivaroxaban was associated with higher rates of major bleeding compared to other DOACs and lower rates of myocardial infarction compared to dabigatran. These results may help guide oral anticoagulant selection, especially in patients at high risk of bleeding or myocardial infarction.