Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis

Anticoagulants are the mainstay for the prevention and treatment of thrombosis. However, bleeding complications remain a primary concern. Recent advances in understanding the contribution of activated factor XI (FXIa) in arterial thrombosis with a limited impact on hemostasis have led to the develop...

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Main Author: Wichaiyo S.
Other Authors: Mahidol University
Format: Review
Published: 2023
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/88084
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spelling th-mahidol.880842023-07-25T01:01:42Z Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis Wichaiyo S. Mahidol University Medicine Anticoagulants are the mainstay for the prevention and treatment of thrombosis. However, bleeding complications remain a primary concern. Recent advances in understanding the contribution of activated factor XI (FXIa) in arterial thrombosis with a limited impact on hemostasis have led to the development of several FXIa-targeting modalities. Injectable agents including monoclonal antibodies and antisense oligonucleotides against FXIa have been primarily studied in venous thrombosis. The orally active small molecules that specifically inhibit the active site of FXIa are currently being investigated for their antithrombotic activity in both arteries and veins. This review focuses on a discussion of the potential clinical benefits of small molecule FXIa inhibitors, mainly asundexian and milvexian, in arterial thrombosis based on their pharmacological profiles and the compelling results of phase 2 clinical studies. The preclinical and epidemiological basis for the impact of FXIa in hemostasis and arterial thrombosis is also addressed. In recent clinical study results, asundexian appears to reduce ischemic events in patients with myocardial infarction and minor-to-moderate stroke, whereas milvexian possibly provides benefits in patients with minor stroke or high-risk transient ischemic attack (TIA). In addition, asundexian and milvexian had a minor impact on hemostasis even in combination with dual-antiplatelet therapy. Other orally active FXIa inhibitors also produce antithrombotic activity in vivo with low bleeding risk. Therefore, FXIa inhibitors might represent a new class of direct-acting oral anticoagulants (DOACs) for the treatment of thrombosis, although the explicit clinical positions of asundexian and milvexian in patients with ischemic stroke, high-risk TIA, and coronary artery disease require confirmation from the outcomes of ongoing phase 3 trials. 2023-07-24T18:01:42Z 2023-07-24T18:01:42Z 2023-01-01 Review ACS Pharmacology and Translational Science (2023) 10.1021/acsptsci.3c00052 25759108 2-s2.0-85164958569 https://repository.li.mahidol.ac.th/handle/123456789/88084 SCOPUS
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
topic Medicine
spellingShingle Medicine
Wichaiyo S.
Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis
description Anticoagulants are the mainstay for the prevention and treatment of thrombosis. However, bleeding complications remain a primary concern. Recent advances in understanding the contribution of activated factor XI (FXIa) in arterial thrombosis with a limited impact on hemostasis have led to the development of several FXIa-targeting modalities. Injectable agents including monoclonal antibodies and antisense oligonucleotides against FXIa have been primarily studied in venous thrombosis. The orally active small molecules that specifically inhibit the active site of FXIa are currently being investigated for their antithrombotic activity in both arteries and veins. This review focuses on a discussion of the potential clinical benefits of small molecule FXIa inhibitors, mainly asundexian and milvexian, in arterial thrombosis based on their pharmacological profiles and the compelling results of phase 2 clinical studies. The preclinical and epidemiological basis for the impact of FXIa in hemostasis and arterial thrombosis is also addressed. In recent clinical study results, asundexian appears to reduce ischemic events in patients with myocardial infarction and minor-to-moderate stroke, whereas milvexian possibly provides benefits in patients with minor stroke or high-risk transient ischemic attack (TIA). In addition, asundexian and milvexian had a minor impact on hemostasis even in combination with dual-antiplatelet therapy. Other orally active FXIa inhibitors also produce antithrombotic activity in vivo with low bleeding risk. Therefore, FXIa inhibitors might represent a new class of direct-acting oral anticoagulants (DOACs) for the treatment of thrombosis, although the explicit clinical positions of asundexian and milvexian in patients with ischemic stroke, high-risk TIA, and coronary artery disease require confirmation from the outcomes of ongoing phase 3 trials.
author2 Mahidol University
author_facet Mahidol University
Wichaiyo S.
format Review
author Wichaiyo S.
author_sort Wichaiyo S.
title Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis
title_short Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis
title_full Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis
title_fullStr Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis
title_full_unstemmed Determination of the Potential Clinical Benefits of Small Molecule Factor XIa Inhibitors in Arterial Thrombosis
title_sort determination of the potential clinical benefits of small molecule factor xia inhibitors in arterial thrombosis
publishDate 2023
url https://repository.li.mahidol.ac.th/handle/123456789/88084
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