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Factor XI and XIa inhibition: a new approach to anticoagulant therapy.凝血因子XI及XIa抑制：抗凝治疗的新方法。
Br J Cardiol. 2024 May 14;31(2):018. doi: 10.5837/bjc.2024.018. eCollection 2024.
2
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3
Recent advances in the discovery and development of factor XI/XIa inhibitors.近年来，因子 XI/XIa 抑制剂的发现和开发取得了新进展。
Med Res Rev. 2018 Sep;38(6):1974-2023. doi: 10.1002/med.21503. Epub 2018 May 4.
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Clinical Evaluation of Factor XIa Inhibitor Drugs: JACC Review Topic of the Week.因子 XIa 抑制剂药物的临床评估：JACC 本周综述主题。
J Am Coll Cardiol. 2023 Feb 28;81(8):771-779. doi: 10.1016/j.jacc.2022.11.057.
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Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders.凝血因子XI抑制剂的临床药理学：预防静脉和动脉血栓性疾病的新治疗方法
J Clin Med. 2022 Oct 26;11(21):6314. doi: 10.3390/jcm11216314.
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Factor XI/XIa Inhibition: The Arsenal in Development for a New Therapeutic Target in Cardio- and Cerebrovascular Disease.因子XI/XIa抑制：心血管和脑血管疾病新治疗靶点的研发武器库。
J Cardiovasc Dev Dis. 2022 Dec 6;9(12):437. doi: 10.3390/jcdd9120437.
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Pharmacology and Clinical Development of Factor XI Inhibitors.因子 XI 抑制剂的药理学和临床开发。
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Development of new anticoagulant in 2023: Prime time for anti-factor XI and XIa inhibitors.2023 年新型抗凝药物的研发：抗因子 XI 和因子 XIa 抑制剂的黄金时代。
J Med Vasc. 2023 Apr;48(2):69-80. doi: 10.1016/j.jdmv.2023.04.002. Epub 2023 May 5.
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Fluorescent Activity-Based Probe To Image and Inhibit Factor XIa Activity in Human Plasma.用于在人血浆中成像和抑制因子 XIa 活性的荧光活性探针。
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A review of emerging factor XI inhibitors.新型凝血因子XI抑制剂综述
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本文引用的文献

1
Factor XI Inhibitors in Early Clinical Trials: A Meta-analysis.早期临床试验中的因子 XI 抑制剂：荟萃分析。
Thromb Haemost. 2023 Jun;123(6):576-584. doi: 10.1055/a-2043-0346. Epub 2023 Feb 25.
2
Effects of rifampin on the pharmacokinetics and pharmacodynamics of milvexian, a potent, selective, oral small molecule factor XIa inhibitor.利福平对米伏先（一种强效、选择性、口服小分子因子 Xa 抑制剂）的药代动力学和药效学的影响。
Sci Rep. 2022 Dec 23;12(1):22239. doi: 10.1038/s41598-022-25936-2.
3
Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial.急性非心源性缺血性脑卒中后用 asundexian 抑制因子 XIa（PACIFIC-Stroke）：一项国际、随机、双盲、安慰剂对照、2b 期试验。
Lancet. 2022 Sep 24;400(10357):997-1007. doi: 10.1016/S0140-6736(22)01588-4. Epub 2022 Sep 2.
4
A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction.一项多中心、2期、随机、安慰剂对照、双盲、平行组、剂量探索性试验，旨在研究口服凝血因子XIa抑制剂阿孙德西安预防急性心肌梗死后不良心血管事件的效果。
Circulation. 2022 Oct 18;146(16):1196-1206. doi: 10.1161/CIRCULATIONAHA.122.061612. Epub 2022 Aug 27.
5
Factor XI Inhibitors for Prevention and Treatment of Venous Thromboembolism: A Review on the Rationale and Update on Current Evidence.用于预防和治疗静脉血栓栓塞的凝血因子XI抑制剂：理论依据综述及当前证据更新
Front Cardiovasc Med. 2022 May 12;9:903029. doi: 10.3389/fcvm.2022.903029. eCollection 2022.
6
Effects of Itraconazole and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Milvexian, A Factor XIa Inhibitor.伊曲康唑和地尔硫䓬对XIa因子抑制剂米尔韦克辛药代动力学和药效学的影响。
Cardiol Ther. 2022 Sep;11(3):407-419. doi: 10.1007/s40119-022-00266-6. Epub 2022 May 31.
7
Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study.口服因子 XIa 抑制剂 asundexian 与房颤患者的阿哌沙班（PACIFIC-AF）相比的安全性：一项多中心、随机、双盲、双模拟、剂量发现的 2 期研究。
Lancet. 2022 Apr 9;399(10333):1383-1390. doi: 10.1016/S0140-6736(22)00456-1. Epub 2022 Apr 3.
8
Single-Dose Pharmacokinetics of Milvexian in Participants with Mild or Moderate Hepatic Impairment Compared with Healthy Participants.轻度或中度肝损伤参与者与健康参与者单次剂量米尔维生的药代动力学比较。
Clin Pharmacokinet. 2022 Jun;61(6):857-867. doi: 10.1007/s40262-022-01110-9. Epub 2022 Mar 9.
9
Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXI in Patients With ESRD.终末期肾病患者中凝血因子 XI 反义抑制剂 IONIS-FXI 的 2 期研究。
Kidney Int Rep. 2021 Nov 24;7(2):200-209. doi: 10.1016/j.ekir.2021.11.011. eCollection 2022 Feb.
10
Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study.新型活化因子 XI 抑制剂 BAY 2433334 在健康志愿者中的药代动力学、药效学和安全性：一项随机、多剂量的 1 期研究。
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凝血因子XI及XIa抑制：抗凝治疗的新方法。

Factor XI and XIa inhibition: a new approach to anticoagulant therapy.

作者信息

Sammut Mark Anthony, Elamin Nadir, Storey Robert F

机构信息

Specialist Registrar in Cardiology and Clinical Research Fellow.

Specialist Registrar in Cardiology.

出版信息

Br J Cardiol. 2024 May 14;31(2):018. doi: 10.5837/bjc.2024.018. eCollection 2024.

DOI:10.5837/bjc.2024.018
PMID:39555467
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11562565/
Abstract

Factor (F) XI or XIa inhibition has Fattracted interest due to the protection from thrombotic events and minimal bleeding tendency observed in FXI-deficient individuals. The prospect of uncoupling the management of thrombosis from the bleeding risk inadvertently associated with current therapy inspired the development of agents directed towards this step in the coagulation process. This review describes the physiological rationale behind FXI/FXIa inhibition and the pharmacological properties of existing FXI/FXIa inhibitors. It also explores the potential clinical use of these agents in various thromboembolic pathologies, predominantly through the phase II clinical trials conducted so far comparing them to current anticoagulant therapy or placebo.

摘要

由于在缺乏因子（F）XI的个体中观察到对血栓形成事件的保护作用以及最小的出血倾向，XI因子或XIa因子抑制已引起关注。将血栓形成的管理与当前治疗无意中关联的出血风险相分离的前景，激发了针对凝血过程这一步骤的药物开发。本综述描述了XI因子/XIa因子抑制背后的生理原理以及现有XI因子/XIa因子抑制剂的药理学特性。它还探讨了这些药物在各种血栓栓塞性疾病中的潜在临床应用，主要是通过迄今为止进行的将它们与当前抗凝治疗或安慰剂进行比较的II期临床试验。