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Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis

Introduction: Despite preventive measures, stroke rates remain high in the primary and secondary prevention settings. Factor XIa inhibition may offer a novel, safe and effective antithrombotic option for stroke prevention. Methods: We conducted a systematic review and meta-analysis including all ava...

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Autores principales: Palaiodimou, Lina, Papagiannopoulou, Georgia, Katsanos, Aristeidis H., Eleftheriou, Andreas, Karapanayiotides, Theodore, Mitsias, Panayiotis D., Lemmens, Robin, Molina, Carlos A., Alexandrov, Andrei, Caso, Valeria, Shoamanesh, Ashkan, Sharma, Mukul, Tsivgoulis, Georgios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10488897/
https://www.ncbi.nlm.nih.gov/pubmed/37685629
http://dx.doi.org/10.3390/jcm12175562
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author Palaiodimou, Lina
Papagiannopoulou, Georgia
Katsanos, Aristeidis H.
Eleftheriou, Andreas
Karapanayiotides, Theodore
Mitsias, Panayiotis D.
Lemmens, Robin
Molina, Carlos A.
Alexandrov, Andrei
Caso, Valeria
Shoamanesh, Ashkan
Sharma, Mukul
Tsivgoulis, Georgios
author_facet Palaiodimou, Lina
Papagiannopoulou, Georgia
Katsanos, Aristeidis H.
Eleftheriou, Andreas
Karapanayiotides, Theodore
Mitsias, Panayiotis D.
Lemmens, Robin
Molina, Carlos A.
Alexandrov, Andrei
Caso, Valeria
Shoamanesh, Ashkan
Sharma, Mukul
Tsivgoulis, Georgios
author_sort Palaiodimou, Lina
collection PubMed
description Introduction: Despite preventive measures, stroke rates remain high in the primary and secondary prevention settings. Factor XIa inhibition may offer a novel, safe and effective antithrombotic option for stroke prevention. Methods: We conducted a systematic review and meta-analysis including all available randomized controlled clinical trials (RCTs) that investigated the efficacy and safety of factor XIa inhibitors versus controls in primary or secondary stroke prevention. The primary efficacy and safety outcomes of interest were symptomatic ischemic stroke (IS) and the composite of major bleeding and clinically relevant non-major bleeding. Results: Four phase II dose-finding RCTs were included, comprising a total of 4732 patients treated with factor XIa inhibitors versus 1798 controls. Treatment with factor XIa inhibitors did not reduce the risk of IS compared to controls (RR: 0.89; 95% CI: 0.67–1.17). The composite of symptomatic IS and covert infarcts on brain MRI (RR: 1.01; 95% CI: 0.87–1.18), the composite of symptomatic IS and transient ischemic attack (TIA; RR: 0.78; 95% CI: 0.61–1.01), and the composite of major adverse cardiovascular events (RR: 1.07; 95% CI: 0.87–1.31) did not differ between the treatment groups. Treatment with factor XIa inhibitors did not increase the risk of the composite of major bleeding and clinically relevant non-major bleeding (RR: 1.19; 95% CI: 0.65–2.16), major bleeding alone (RR: 1.19; 95% CI: 0.64–2.22), intracranial bleeding (RR: 0.91; 95% CI: 0.26–3.19) or all-cause mortality (RR: 1.21; 95% CI: 0.77–1.90). Conclusion: This meta-analysis provides reassuring evidence regarding the safety of factor XIa inhibitors. These findings, coupled with potential signals of efficacy in reducing IS (and TIA), underscore the importance of ongoing phase III RCTs for providing definitive data regarding the effect of factor XIa inhibition on stroke prevention.
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spelling pubmed-104888972023-09-09 Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis Palaiodimou, Lina Papagiannopoulou, Georgia Katsanos, Aristeidis H. Eleftheriou, Andreas Karapanayiotides, Theodore Mitsias, Panayiotis D. Lemmens, Robin Molina, Carlos A. Alexandrov, Andrei Caso, Valeria Shoamanesh, Ashkan Sharma, Mukul Tsivgoulis, Georgios J Clin Med Systematic Review Introduction: Despite preventive measures, stroke rates remain high in the primary and secondary prevention settings. Factor XIa inhibition may offer a novel, safe and effective antithrombotic option for stroke prevention. Methods: We conducted a systematic review and meta-analysis including all available randomized controlled clinical trials (RCTs) that investigated the efficacy and safety of factor XIa inhibitors versus controls in primary or secondary stroke prevention. The primary efficacy and safety outcomes of interest were symptomatic ischemic stroke (IS) and the composite of major bleeding and clinically relevant non-major bleeding. Results: Four phase II dose-finding RCTs were included, comprising a total of 4732 patients treated with factor XIa inhibitors versus 1798 controls. Treatment with factor XIa inhibitors did not reduce the risk of IS compared to controls (RR: 0.89; 95% CI: 0.67–1.17). The composite of symptomatic IS and covert infarcts on brain MRI (RR: 1.01; 95% CI: 0.87–1.18), the composite of symptomatic IS and transient ischemic attack (TIA; RR: 0.78; 95% CI: 0.61–1.01), and the composite of major adverse cardiovascular events (RR: 1.07; 95% CI: 0.87–1.31) did not differ between the treatment groups. Treatment with factor XIa inhibitors did not increase the risk of the composite of major bleeding and clinically relevant non-major bleeding (RR: 1.19; 95% CI: 0.65–2.16), major bleeding alone (RR: 1.19; 95% CI: 0.64–2.22), intracranial bleeding (RR: 0.91; 95% CI: 0.26–3.19) or all-cause mortality (RR: 1.21; 95% CI: 0.77–1.90). Conclusion: This meta-analysis provides reassuring evidence regarding the safety of factor XIa inhibitors. These findings, coupled with potential signals of efficacy in reducing IS (and TIA), underscore the importance of ongoing phase III RCTs for providing definitive data regarding the effect of factor XIa inhibition on stroke prevention. MDPI 2023-08-26 /pmc/articles/PMC10488897/ /pubmed/37685629 http://dx.doi.org/10.3390/jcm12175562 Text en © 2023 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 Systematic Review
Palaiodimou, Lina
Papagiannopoulou, Georgia
Katsanos, Aristeidis H.
Eleftheriou, Andreas
Karapanayiotides, Theodore
Mitsias, Panayiotis D.
Lemmens, Robin
Molina, Carlos A.
Alexandrov, Andrei
Caso, Valeria
Shoamanesh, Ashkan
Sharma, Mukul
Tsivgoulis, Georgios
Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis
title Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis
title_full Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis
title_fullStr Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis
title_full_unstemmed Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis
title_short Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis
title_sort efficacy and safety of oral factor xia inhibitors in stroke prevention: a systematic review and meta-analysis
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10488897/
https://www.ncbi.nlm.nih.gov/pubmed/37685629
http://dx.doi.org/10.3390/jcm12175562
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