Pharmacological and clinical appraisal of factor XI inhibitor drugs.

IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS European Heart Journal - Cardiovascular Pharmacotherapy Pub Date : 2024-05-04 DOI:10.1093/ehjcvp/pvae002
Giovanni Occhipinti, Claudio Laudani, Marco Spagnolo, Simone Finocchiaro, Placido Maria Mazzone, Denise Cristiana Faro, Maria Sara Mauro, Carla Rochira, Federica Agnello, Daniele Giacoppo, Nicola Ammirabile, Davide Landolina, Antonino Imbesi, Giuseppe Sangiorgio, Antonio Greco, Davide Capodanno
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Abstract

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.

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因子 XI 抑制剂药物的药理和临床评估。
从维生素 K 拮抗剂到近二十年前出现的直接口服抗凝剂 (DOAC),抗凝疗法的演变标志着重大进展。尽管关键试验和上市后观察结果表明安全性有所提高,但人们对其的担忧依然存在,尤其是出血风险以及在特定亚组或临床环境中缺乏治疗适应症等问题。因子 XI(FXI)近来已成为腔内血栓形成和生长的关键因素,在封闭血管壁损伤方面作用有限。抑制 FXI 为血栓形成与止血脱钩提供了机会,既能解决与出血事件相关的问题,又能防止血栓栓塞事件的发生。值得注意的是,FXI 抑制剂有望用于终末期肾病或癌症患者,而目前 DOACs 还缺乏明确的适应症。各种化合物都经过了设计、测试并进入了 2 期临床试验,显示出普遍良好的安全性和耐受性。然而,还需要通过大规模的 3 期临床试验进行验证,这些试验需要有足够的力量来评估安全性和疗效。本综述全面研究了 FXI 抑制剂,深入探讨了各个类别,探究了它们的药理特性,评估了随机试验的最新证据,并对未来前景提出了见解。
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来源期刊
European Heart Journal - Cardiovascular Pharmacotherapy
European Heart Journal - Cardiovascular Pharmacotherapy Medicine-Cardiology and Cardiovascular Medicine
CiteScore
10.10
自引率
14.10%
发文量
65
期刊介绍: The European Heart Journal - Cardiovascular Pharmacotherapy (EHJ-CVP) is an international, peer-reviewed journal published in English, specifically dedicated to clinical cardiovascular pharmacology. EHJ-CVP publishes original articles focusing on clinical research involving both new and established drugs and methods, along with meta-analyses and topical reviews. The journal's primary aim is to enhance the pharmacological treatment of patients with cardiovascular disease by interpreting and integrating new scientific developments in this field. While the emphasis is on clinical topics, EHJ-CVP also considers basic research articles from fields such as physiology and molecular biology that contribute to the understanding of cardiovascular drug therapy. These may include articles related to new drug development and evaluation, the physiological and pharmacological basis of drug action, metabolism, drug interactions, and side effects.
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