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Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders

Bleeding is the dominant adverse event of anticoagulation and often discourages many patients and physicians from starting treatment with anticoagulant drugs. The fact that factor (F)XI deficiency is associated with a mild bleeding phenotype and that FXI knockdown or inhibition in different animal m...

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Autores principales: Campello, Elena, Simioni, Paolo, Prandoni, Paolo, Ferri, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654315/
https://www.ncbi.nlm.nih.gov/pubmed/36362541
http://dx.doi.org/10.3390/jcm11216314
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author Campello, Elena
Simioni, Paolo
Prandoni, Paolo
Ferri, Nicola
author_facet Campello, Elena
Simioni, Paolo
Prandoni, Paolo
Ferri, Nicola
author_sort Campello, Elena
collection PubMed
description Bleeding is the dominant adverse event of anticoagulation and often discourages many patients and physicians from starting treatment with anticoagulant drugs. The fact that factor (F)XI deficiency is associated with a mild bleeding phenotype and that FXI knockdown or inhibition in different animal models reduced the occurrence of thrombotic events in response to injury suggests that FXI is more important for the coagulation propagation and thrombotic process than for the overall hemostasis. The aim of this review is to summarize clinical pharmacology and evidence from phase 2 clinical trials on efficacy and safety of drugs directed against FXI for the treatment and prevention of thrombosis. Inhibition of FXI or FXIa has been proven to be effective in phase 2 studies at preventing venous thromboembolism (VTE) in patients undergoing total knee arthroplasty, or for prevention of major adverse vascular events in patients with end-stage kidney disease undergoing hemodialysis or as adjuncts to antiplatelet therapy for prevention of recurrent ischemic events in patients with acute myocardial infarction or non-cardioembolic stroke. Should the efficacy of FXI inhibitors as anticoagulant without impairing the hemostasis be proven in phase 3 randomized clinical trials, it would provide an innovative therapeutic option.
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spelling pubmed-96543152022-11-15 Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders Campello, Elena Simioni, Paolo Prandoni, Paolo Ferri, Nicola J Clin Med Article Bleeding is the dominant adverse event of anticoagulation and often discourages many patients and physicians from starting treatment with anticoagulant drugs. The fact that factor (F)XI deficiency is associated with a mild bleeding phenotype and that FXI knockdown or inhibition in different animal models reduced the occurrence of thrombotic events in response to injury suggests that FXI is more important for the coagulation propagation and thrombotic process than for the overall hemostasis. The aim of this review is to summarize clinical pharmacology and evidence from phase 2 clinical trials on efficacy and safety of drugs directed against FXI for the treatment and prevention of thrombosis. Inhibition of FXI or FXIa has been proven to be effective in phase 2 studies at preventing venous thromboembolism (VTE) in patients undergoing total knee arthroplasty, or for prevention of major adverse vascular events in patients with end-stage kidney disease undergoing hemodialysis or as adjuncts to antiplatelet therapy for prevention of recurrent ischemic events in patients with acute myocardial infarction or non-cardioembolic stroke. Should the efficacy of FXI inhibitors as anticoagulant without impairing the hemostasis be proven in phase 3 randomized clinical trials, it would provide an innovative therapeutic option. MDPI 2022-10-26 /pmc/articles/PMC9654315/ /pubmed/36362541 http://dx.doi.org/10.3390/jcm11216314 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Campello, Elena
Simioni, Paolo
Prandoni, Paolo
Ferri, Nicola
Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders
title Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders
title_full Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders
title_fullStr Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders
title_full_unstemmed Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders
title_short Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders
title_sort clinical pharmacology of factor xi inhibitors: new therapeutic approaches for prevention of venous and arterial thrombotic disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654315/
https://www.ncbi.nlm.nih.gov/pubmed/36362541
http://dx.doi.org/10.3390/jcm11216314
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