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.

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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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