Update on the cardiovascular application of targeting factor XI

Abstract

Cardiovascular diseases remain the leading global cause of morbidity and mortality, and thrombotic events contribute substantially to their clinical burden. Established anticoagulants, including vitamin K antagonists and direct oral anticoagulants, reduce thromboembolic events but remain limited by bleeding risk in selected patients. Factor XI (FXI), a serine protease in the intrinsic coagulation pathway, has emerged as a promising investigational target because FXI-dependent thrombin amplification appears to contribute more to pathological thrombosis than to physiological hemostasis. This review consolidates contemporary progress in FXI/activated factor XI (FXIa)-targeted therapeutics, encompassing monoclonal antibodies (e.g., abelacimab, osocimab), antisense oligonucleotides (e.g., fesomersen), and small-molecule inhibitors (e.g., milvexian, asundexian). Clinical evidence suggests that FXI/FXIa inhibition may reduce thrombosis or bleeding in selected settings, particularly postoperative venous thromboembolism prophylaxis and certain high-bleeding-risk populations; however, efficacy signals have been inconsistent across indications such as atrial fibrillation, acute coronary syndrome, and secondary stroke prevention. Remaining challenges, including long-term safety, dose selection, patient stratification, perioperative management, and definitive efficacy in outcome trials, are also discussed. Overall, FXI/FXIa inhibition remains a promising but still investigational strategy that may improve the balance between antithrombotic efficacy and bleeding risk in selected clinical contexts.