Update on the cardiovascular application of targeting factor XI

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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.