Development of new anticoagulants targeting coagulation factor XI and prospects for clinical use.

IF 2.5 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Masahiro Ieko, Kazumasa Ohmura, Sumiyoshi Naito, Mika Yoshida, Osamu Kumano
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引用次数: 0

Abstract

Thrombosis is a potentially fatal condition for which various anticoagulant therapies have been used for prevention and treatment. However, bleeding events remain a concern with all anticoagulant drugs. Recent evidence suggests that inhibiting coagulation factor XI (FXI) and activated FXI (FXIa) plays a greater role in the formation of pathological thrombi in thrombosis than in normal hemostatic thrombi, allowing for the potential to address these two events separately. Consequently, FXI/XIa inhibition has become the focus of anticoagulant drug research, leading to the development of numerous FXI-targeting compounds with diverse mechanisms of action. Herein, we aimed to review FXI/FXIa inhibitors under development, discussing the role of FXI in the coagulation reaction and the advantages and disadvantages associated with its deficiency. The results of a Phase II study showed that FXI/XIa inhibitors provide efficacy comparable to that of low molecular weight heparin therapy while reducing clinically significant bleeding events. Additionally, in a study of patients with atrial fibrillation, FXI/XIa inhibitors reduced bleeding events compared to those with direct oral anticoagulants. Furthermore, when combined with antiplatelet therapy, FXI/XIa inhibitors did not significantly increase bleeding risk in non-cardioembolic stroke or acute coronary syndrome. However, conflicting trial results have also been reported, highlighting the difficulty in assessing the clinical benefit of FXI/XIa inhibitors in different clinical settings, such as atrial fibrillation and acute myocardial infarction. Future large, well-designed Phase III studies are needed to evaluate the safety and efficacy of FXI/XIa inhibitors across diverse populations requiring antithrombotic therapy.

以凝血因子XI为靶点的新型抗凝剂的研制及临床应用前景。
血栓形成是一种潜在的致命疾病,各种抗凝治疗已被用于预防和治疗。然而,出血事件仍然是所有抗凝药物关注的问题。最近的证据表明,抑制凝血因子XI (FXI)和活化的FXI (FXIa)在血栓形成中比在正常的止血血栓形成中发挥更大的作用,从而有可能分别解决这两个事件。因此,FXI/XIa抑制已成为抗凝药物研究的重点,许多FXI靶向化合物的开发具有不同的作用机制。在此,我们旨在回顾正在开发的FXI/FXIa抑制剂,讨论FXI在凝血反应中的作用及其不足的优缺点。一项II期研究结果显示,FXI/XIa抑制剂的疗效与低分子肝素治疗相当,同时减少了临床显著的出血事件。此外,在一项心房颤动患者的研究中,与直接口服抗凝剂相比,FXI/XIa抑制剂可减少出血事件。此外,当与抗血小板治疗联合使用时,FXI/XIa抑制剂不会显著增加非心源性卒中或急性冠状动脉综合征的出血风险。然而,也报道了相互矛盾的试验结果,突出了评估FXI/XIa抑制剂在不同临床环境(如房颤和急性心肌梗死)中的临床益处的困难。未来需要大规模、精心设计的III期研究来评估FXI/XIa抑制剂在需要抗血栓治疗的不同人群中的安全性和有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of cardiology
Journal of cardiology CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
4.90
自引率
8.00%
发文量
202
审稿时长
29 days
期刊介绍: The official journal of the Japanese College of Cardiology is an international, English language, peer-reviewed journal publishing the latest findings in cardiovascular medicine. Journal of Cardiology (JC) aims to publish the highest-quality material covering original basic and clinical research on all aspects of cardiovascular disease. Topics covered include ischemic heart disease, cardiomyopathy, valvular heart disease, vascular disease, hypertension, arrhythmia, congenital heart disease, pharmacological and non-pharmacological treatment, new diagnostic techniques, and cardiovascular imaging. JC also publishes a selection of review articles, clinical trials, short communications, and important messages and letters to the editor.
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