Abstract Body: Background: Stroke is the second leading cause of death worldwide, with atrial fibrillation being a significant risk factor that substantially increases the likelihood of stroke. Although many observational studies have assessed the effectiveness of apixaban, a widely used direct oral anticoagulant (DOAC), in preventing stroke in atrial fibrillation, there is limited evidence from randomized controlled trials (RCTs).

Objectives: We aimed to integrate findings from RCTs to compare the efficacy and safety of apixaban with the standard of care (SOC)—antiplatelet therapy (aspirin) or vitamin K antagonists (warfarin)—for stroke prevention in atrial fibrillation.

Methods: We analyzed the data using RevMan 5.4 with a random effects model, pooling outcomes as hazard ratios (HR) with 95% confidence intervals (CI). The primary efficacy outcome of the study was the composite endpoint of either stroke or systemic embolism. The primary safety outcome was major bleeding. Our study protocol is registered in PROSPERO (CRD42024572983).

Results: Our analysis included 6 RCTs involving 33,000 participants, an average age of 71.3 years, and follow-up periods ranging from 6 months to 3.5 years. The pooled analysis revealed a statistically significant reduction in the composite outcome of stroke or systemic embolism for patients on apixaban compared to SOC, with an HR of 0.62 (95% CI: 0.44 to 0.87, p = 0.005). No significant difference was observed in major bleeding events between apixaban and SOC, with an HR of 0.93 (95% CI: 0.63 to 1.38, p = 0.72). For secondary outcomes, apixaban did not show a significant impact on all-cause mortality (HR: 0.92; 95% CI: 0.83 to 1.03, p = 0.13) or cardiovascular mortality (HR: 0.92; 95% CI: 0.81 to 1.05, p = 0.22).

Conclusion: In patients with atrial fibrillation, apixaban was superior to aspirin or warfarin in preventing stroke or systemic embolism. However, no significant differences were found in major bleeding, all-cause mortality, or cardiovascular mortality when comparing apixaban to standard of care. Further randomized controlled trials with longer follow-ups are needed to assess the potential long-term effects and benefits of apixaban.