Factor XI/XIa inhibitors reduced major bleeding risk by 61% (RR 0.39) versus Factor Xa inhibitors in AF patients, with no difference in mortality or adverse events.
Do Factor XI/XIa inhibitors reduce major bleeding compared to Factor Xa inhibitors in patients with atrial fibrillation requiring stroke prevention?
Factor XI/XIa inhibitors significantly reduce the risk of major bleeding compared to Factor Xa inhibitors in patients with atrial fibrillation, without differences in all-cause mortality or overall adverse events.
Abstract Background Stroke prevention in atrial fibrillation (AF) patients is commonly managed with direct oral anticoagulants (DOACs), which carry an inherent risk of bleeding. We aimed to compare the safety of Factor XI/XIa inhibitors to DOACs, specifically focusing on the risk of major bleeding complications. Purpose We conducted a meta-analysis to assess the safety and efficacy of Factor XI/XIa inhibitors in patients with AF requiring stroke prevention. Methods We conducted a systematic search of different databases for randomized controlled trials (RCTs) comparing Factor XI/XIa to DOACs for stroke prophylaxis in AF Patients. Statistical analysis was performed using R, with Risk Ratios (RR) calculated using a random-effects model. Heterogeneity was assessed using I² and Chi² indices. Results Three RCTs comprising 16,772 patients with AF were included. Of the participants studied, 8,728 (52%) received Factor XI/XIa inhibitors, and 8,044 (48%) received DOACs. Overall, Factor XI/XIa inhibitors were associated with a significantly lower risk of major bleedings (RR 0.39, 95% confidence interval CI 0.29–0.53; p 0.01; I² = 2.8%) compared to Factor Xa inhibitors. There was no significant difference in all-cause mortality between the groups (RR 0.85, 95% CI 0.63–1.15; p = 0.29; I² = 0.0%). Adverse events occurred at similar rates in both treatment arms, with no statistically significant differences observed (RR 1.01, 95% CI 0.97–1.05; p = 0.61; I² = 0.0%). Conclusion This meta-analysis shows that Factor XI/XIa inhibitors significantly reduce the risk of major and clinically relevant non-major bleeding compared to Factor Xa inhibitors, with no significant differences in all-cause mortality or adverse events. These findings highlight Factor XI/XIa inhibitors as promising alternatives for anticoagulation therapy in AF, particularly for patients at high risk of bleeding.
Walia et al. (2025) studied this question. Factor XI/XIa inhibitors reduced major bleeding risk by 61% (RR 0.39) versus Factor Xa inhibitors in AF patients, with no difference in mortality or adverse events.