A Systematic Review of Factor XI/XIa Inhibitors Versus Direct Oral Anticoagulants in Patients with Atrial Fibrillation.

BackgroundAtrial fibrillation (AF) is a leading cause of stroke, necessitating effective anticoagulation. While direct oral anticoagulants (DOACs) have improved stroke prevention, bleeding risks remain a concern. Factor XI/XIa inhibitors, targeting the intrinsic coagulation pathway, offer potential for reduced bleeding, although questions remain regarding their efficacy. This systematic review evaluates the efficacy and safety of Factor XI/XIa inhibitors compared to DOACs in AF patients.MethodsWe conducted a systematic review of randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients, identified through PubMed and Embase up to January 2025. Data were synthesized narratively due to heterogeneity in study designs and outcomes.ResultsThree RCTs (AZALEA-TIMI 71, OCEANIC-AF, PACIFIC-AF) involving 16 852 patients were included. Factor XI/XIa inhibitors (abelacimab and asundexian) demonstrated significant reductions in bleeding compared to DOACs. In AZALEA-TIMI 71, abelacimab reduced major or clinically relevant non-major bleeding by 62%-69% versus rivaroxaban. In PACIFIC-AF, asundexian reduced bleeding by 50%-84% compared to apixaban. However, OCEANIC-AF showed asundexian was inferior in stroke prevention, with a 3.8-fold higher risk of stroke or systemic embolism compared to apixaban, leading to early trial termination. Abelacimab showed a trend toward higher ischemic stroke rates abelacimab (150 mg: 1.21 vs 0.59 events/100 person-years; and 90 mg: 1.24 vs 0.59 events/100 person-years), though not statistically significant.ConclusionFactor XI/XIa inhibitors significantly reduce bleeding risk in AF patients compared to DOACs, but their thrombotic efficacy remains uncertain. While promising, further research is needed to optimize their use.