Factor XI/XIa inhibitors reduced major bleeding risk by 59% compared to DOACs but increased ischemic stroke risk over threefold in patients with atrial fibrillation at high thromboembolic risk.
Meta-Analysis (n=16,772)
Yes
Do Factor XI/XIa inhibitors reduce bleeding and prevent stroke compared to DOACs in patients with atrial fibrillation?
Factor XI/XIa inhibitors significantly reduce major bleeding compared to DOACs in atrial fibrillation but are associated with a concerning increase in ischemic stroke and systemic embolism.
Effect estimate: RR 0.41 (95% CI 0.36-0.46)
ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.
Faizan et al. (Sun,) conducted a meta-analysis in Patients with atrial fibrillation at high thromboembolic risk (mean CHA₂DS₂-VASc score 3.9-5) (n=16,772). Factor XI/XIa inhibitors (Asundexian, Abelacimab) vs. Direct oral anticoagulants (DOACs) - Apixaban 5 mg twice daily, Rivaroxaban 20 mg once daily was evaluated on Major bleeding (RR 0.41, 95% CI 0.36-0.46). Factor XI/XIa inhibitors reduced major bleeding risk by 59% compared to DOACs but increased ischemic stroke risk over threefold in patients with atrial fibrillation at high thromboembolic risk.