INTRODUCTION: Atrial fibrillation (AF), a common heart rhythm abnormality, is linked to a higher risk of stroke. Traditionally, warfarin has been the primary anticoagulation treatment for reducing the stroke risk. The new standard of treatment by direct oral anticoagulants (DOACs) offers greater benefits including improved efficacy and fewer adverse effects with reduced monitoring. This study aims to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB) among patients with AF who switched from warfarin to DOACs. METHODS: This study utilized Medicare data to conduct a retrospective analysis of patients with non-valvular atrial fibrillation (NVAF) who switched from warfarin to DOACs between January 1, 2012, and December 31, 2019. Patients with NVAF aged 65 and older who switched from warfarin and had continuous health plan enrollment were included. Descriptive statistics, propensity score matching (PSM), and Cox proportional hazard (PH) models were utilized to compare the outcomes and assess risks of SE and MB across the DOAC cohorts. RESULTS: Among 1,843,495 patients with NVAF on warfarin, 171,700 switched to DOACs within 90 days of discontinuation (apixaban: 90,850
rivaroxaban: 67,698
dabigatran: 12,900). The mean follow-up period across DOAC cohorts ranged from 552 to 628 days. After PSM, apixaban showed significantly lower rates of stroke/SE compared to dabigatran (2.99% vs. 3.98%, p <
0.0001) and rivaroxaban (3.08% vs. 3.80%, p <
0.0001). MB rates were also lower with apixaban versus dabigatran (4.29% vs. 5.57%, p <
0.0001) and rivaroxaban (4.07% vs. 6.35%, p <
0.0001). Cox PH models confirmed these findings, with apixaban demonstrating lower risks of stroke/SE [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.72-0.96 vs. dabigatran
HR 0.91, 95% CI 0.85-0.96 vs. rivaroxaban] and MB (HR 0.79, 95% CI 0.71-0.89 vs. dabigatran
HR 0.68, 95% CI 0.65-0.72 vs. rivaroxaban). CONCLUSION: The risk of stroke/SE and MB varies significantly among patients with NVAF switching from warfarin to different DOACs, with apixaban presenting the lowest risk compared to dabigatran and rivaroxaban.