[2024 年的新型抗凝剂:XI 因子和 XIa 抑制剂的发展]。

Nûn K Bentounes, Sophie Melicine, Anne-Céline Martin, David M Smadja, Nicolas Gendron
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引用次数: 0

摘要

血栓形成仍然是世界上导致死亡的主要原因之一。抗凝治疗的历史已从非特异性药物(即肝素和维生素 K 拮抗剂,VKA)发展到直接针对特异性凝血因子的药物(即阿加曲班、磺达肝癸和直接口服抗凝剂,DOAC)。近十年来,DOAC 因其使用方便、药理作用良好且无需监测而被广泛应用于临床实践。然而,尽管 DOAC 的安全性优于维生素 K 拮抗剂,但其出血风险也不容忽视。目前正在开发针对凝血接触期的新型抗凝剂,从而有可能在不影响止血的情况下预防血栓形成的风险。有关 FXI 缺乏症的流行病学和临床前数据表明,FXI 是一个很有前景的治疗靶点。本综述旨在总结以 FXI/FXIa 抑制为重点的各种临床试验的结果,并强调这一新的抗凝剂治疗类别将面临的挑战。
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[New anticoagulants in 2024: Development of factor XI and XIa inhibitors].

Thrombosis remains one of the leading causes of death in the world. The history of anticoagulation has evolved considerably from non-specific drugs (i.e., heparins and vitamin K antagonists, VKA) to agents that directly target specific coagulation factors (i.e., argatroban, fondaparinux and direct oral anticoagulants, DOAC). Since the last decade, DOAC are widely used in clinical practice because of their ease to use, their favorable pharmacological profile and the fact that they do not require monitoring. However, despite having a better safety profile than vitamin K antagonist, their bleeding risk is not negligible. New anticoagulants targeting the contact phase of coagulation are currently being developed and could make it possible to prevent the risk of thrombosis without impairing hemostasis. Epidemiological and preclinical data on FXI deficiency make FXI a promising therapeutic target. The aim of this review is to summarize the results of the various clinical trials available that focus on FXI/FXIa inhibition, and to highlight the challenges that this new therapeutic class of anticoagulants will face.

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