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阿孙地昔的药代动力学和药效学评价:一种用于预防中风的新型因子XIa抑制剂

A pharmacokinetic and pharmacodynamic evaluation of asundexian: a novel factor XIa inhibitor for stroke prevention.

作者信息

Cella Arianna, Marè Alessandro, Gigli Gian Luigi, Zedde Marialuisa, Valente Mariarosaria, Merlino Giovanni

机构信息

Clinical Neurology, Department of Head, Neck and Neurosciences, Udine University Hospital, Udine, Italy.

DMED, University of Udine, Udine, Italy.

出版信息

Expert Opin Drug Metab Toxicol. 2024 Nov-Dec;20(11-12):1003-1011. doi: 10.1080/17425255.2024.2402496. Epub 2024 Oct 7.

DOI:10.1080/17425255.2024.2402496
PMID:39257338
Abstract

INTRODUCTION

Antithrombotic therapy is the mainstay of ischemic stroke prevention. Current drugs (antiplatelets and oral anticoagulants) lead to increased bleeding risks, and the rates of stroke recurrence, despite antithrombotic therapy, are still elevated. There is a need for novel antithrombotic therapies with superior effectiveness but without increased bleeding risk. Factor XIa inhibitors might cover this gap.

AREAS COVERED

This manuscript examines the pharmacokinetic and pharmacodynamic properties of asundexian and the current clinical evidence regarding its application in preventing ischemic stroke.

EXPERT OPINION

Asundexian shows a very favoring pharmacokinetic profile. Despite asundexian being inferior to apixaban for cardioembolic ischemic stroke, it could be useful in patients with non-cardioembolic ischemic stroke. Although antiplatelet therapy is the recommended treatment to prevent non-cardioembolic ischemic stroke, adding an anticoagulant might have beneficial effects through the dual-pathway inhibition strategy. Due to the potential risk of hemorrhagic transformation, there is hesitation to administer anticoagulants early to patients who have recently had an ischemic stroke, especially if they are also on antiplatelet therapy. However, clinical trials on asundexian confirmed its safety for bleeding, even when used with antiplatelets. A phase 3 trial is currently investigating the efficacy of asundexian in preventing non-cardioembolic ischemic stroke.

摘要

引言

抗栓治疗是缺血性中风预防的主要手段。目前的药物(抗血小板药物和口服抗凝剂)会增加出血风险,并且尽管进行了抗栓治疗,中风复发率仍然很高。需要有疗效更佳且不增加出血风险的新型抗栓疗法。凝血因子 XIa 抑制剂可能填补这一空白。

涵盖领域

本手稿研究了阿孙地昔布的药代动力学和药效学特性以及其在预防缺血性中风应用方面的现有临床证据。

专家意见

阿孙地昔布显示出非常有利的药代动力学特征。尽管在心脏栓塞性缺血性中风方面阿孙地昔布不如阿哌沙班,但它可能对非心脏栓塞性缺血性中风患者有用。虽然抗血小板治疗是预防非心脏栓塞性缺血性中风的推荐治疗方法,但添加抗凝剂可能通过双途径抑制策略产生有益效果。由于存在出血转化的潜在风险,对于近期发生缺血性中风的患者,尤其是同时使用抗血小板药物的患者,早期给予抗凝剂存在犹豫。然而,关于阿孙地昔布的临床试验证实了其出血安全性,即使与抗血小板药物联合使用时也是如此。一项 3 期试验目前正在研究阿孙地昔布预防非心脏栓塞性缺血性中风的疗效。

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