Elsheikh Sandra, Tidbury Nicola, Lip Gregory Y H
Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK.
Cardiology Department, St Helens and Knowsley Teaching Hospitals NHS Trust, Whiston, UK.
Expert Opin Emerg Drugs. 2023 Mar;28(1):43-53. doi: 10.1080/14728214.2023.2192923. Epub 2023 Mar 21.
Whilst the introduction of direct oral anticoagulants (DOACs) has improved the prevention of thromboembolic events, there is still a need for safer anticoagulants. This is particularly so, for specific populations of patients, such as those with an increased bleeding risk or those with severely reduced kidney function. People with Factor XI (FXI) deficiency are at reduced risk of thromboembolic events, without an increased risk of spontaneous bleeding. FXI inhibition, therefore, presents the ideal target for novel anticoagulants.
In this review, we provide an overview of the currently available anticoagulants and the emerging FXIa inhibitors in clinical trials. The need for availability of novel anticoagulants and the potential issues that will hinder the development and marketing of factor XIa inhibitors is also discussed.
Evidence suggests that FXI inhibition presents a promising drug target for novel anticoagulation therapies. The FXIa inhibitors in development have advantages over DOACs with lower renal clearance and long half-lives. Overall, FXI inhibition presents a promising target, it is likely that the clinical use of FXIa inhibitors is on the horizon.
虽然直接口服抗凝剂（DOACs）的引入改善了血栓栓塞事件的预防，但仍需要更安全的抗凝剂。对于特定患者群体，如出血风险增加或肾功能严重降低的患者，情况尤其如此。患有因子XI（FXI）缺乏症的人发生血栓栓塞事件的风险降低，且无自发性出血风险增加。因此，抑制FXI是新型抗凝剂的理想靶点。
在本综述中，我们概述了目前可用的抗凝剂以及临床试验中正在出现的FXIa抑制剂。还讨论了新型抗凝剂可用性的需求以及将阻碍因子XIa抑制剂开发和上市的潜在问题。
证据表明，抑制FXI是新型抗凝治疗的一个有前景的药物靶点。正在开发的FXIa抑制剂比DOACs具有优势，其肾清除率更低，半衰期更长。总体而言，抑制FXI是一个有前景的靶点，FXIa抑制剂的临床应用可能即将到来。
