Real-world comparative effectiveness and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation

Abstract

Background and purpose Long-term oral anticoagulants (OACs), either vitamin K antagonists or direct oral anticoagulants (DOACs), are essential for stroke prevention in atrial fibrillation (AF). However, comparative real-world evidence among DOACs in upper-middle-income settings remains inconsistent. This study compared the effectiveness and safety of DOACs with warfarin in reducing stroke or systemic embolism (SSE), major bleeding, and all-cause mortality in patients with AF. Methods We conducted a retrospective cohort study of patients with non-valvular AF newly prescribed OACs between 2010 and 2021 using the Ramathibodi Hospital database. Inverse probability weighting (IPW) was applied to balance baseline covariates and emulate a RCT. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using IPW-adjusted Cox proportional hazards models. Results Among 5580 patients, 4237 received warfarin, 414 dabigatran, 428 rivaroxaban, 413 apixaban, and 88 edoxaban. Compared with warfarin, apixaban (HR 0.35; 95% CI 0.18, 0.67) was associated with significantly lower risks of SSE. Dabigatran (HR 0.43; 95% CI 0.23, 0.81) and rivaroxaban (HR 0.47; 95% CI 0.25, 0.90) significantly reduced the major bleeding risk. No DOAC was associated with reduced all-cause mortality. Sensitivity analyses confirmed the robustness of the findings. Conclusion Apixaban showed the most favorable profile with significant reductions in SSE and trend toward lower major bleeding compared with warfarin, supporting its preferential use for stroke prevention in this setting.