Tantry Udaya S, Raghavakurup Lekshminarayan, Becker Richard C, Singh Sahib, Bliden Kevin P, Gurbel Paul A
Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA.
Department of Internal Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Expert Opin Pharmacother. 2024 Jul;25(10):1271-1280. doi: 10.1080/14656566.2024.2385062. Epub 2024 Jul 30.
Balancing the prevention of thrombosis with bleeding risk when combining anticoagulants and platelet antagonists remains a concern among clinicians, particularly in patients with acute coronary syndrome (ACS) who are treated with potent antiplatelet therapy. This may be because the available antiplatelet and anticoagulants are unable to uncouple physiological hemostasis and pathological thrombosis. Therefore, their use is associated with an unavoidable elevated risk of bleeding.
Evidence available from studies evaluating FXIa inhibitors and milvexian was collected from a selective literature search. In this review, the authors describe the potential role of FXI/XIa in experimental thrombosis, evidence for FXIa inhibition in the treatment of clinical thrombotic events, and highlight the current evidence supporting the role of milvexian, a novel FXIa inhibitor, in patients with ACS.
The ongoing LIBREXIA-ACS trial is a large-scale study currently investigating milvexian in patients with ACS. This study may support the proof of concept of differentiating physiological hemostasis and pathological thrombosis and achieving maximum antithrombotic efficacy with minimum bleeding risk when used on top of dual antiplatelet therapy with potent P2Y receptor blockers.
在联合使用抗凝剂和血小板拮抗剂时,平衡血栓形成的预防与出血风险仍是临床医生关注的问题,尤其是在接受强效抗血小板治疗的急性冠状动脉综合征(ACS)患者中。这可能是因为现有的抗血小板药物和抗凝剂无法区分生理性止血和病理性血栓形成。因此,它们的使用不可避免地会增加出血风险。
通过选择性文献检索收集了评估FXIa抑制剂和米尔维昔单抗的研究中的现有证据。在本综述中,作者描述了FXI/XIa在实验性血栓形成中的潜在作用、FXIa抑制在治疗临床血栓事件中的证据,并强调了支持新型FXIa抑制剂米尔维昔单抗在ACS患者中作用的当前证据。
正在进行的LIBREXIA-ACS试验是一项大规模研究,目前正在研究米尔维昔单抗在ACS患者中的应用。这项研究可能支持在强效P2Y受体阻滞剂双重抗血小板治疗基础上使用时,区分生理性止血和病理性血栓形成并以最小出血风险实现最大抗血栓疗效这一概念的验证。