Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention : A Systematic Review and Meta-Analysis
Palaiodimou, Lina (University of Athens)
Papagiannopoulou, Georgia (University of Athens)
Katsanos, Aristeidis H. (McMaster University/Population Health Research Institute (Canadà))
Eleftheriou, Andreas (University of Athens)
Karapanayiotides, Theodore (Aristotle University of Thessaloniki)
Mitsias, Panayiotis D. (University Hospital of Heraklion (Heraklion, Grècia))
Lemmens, Robin (UZ Leuven)
Molina, Carlos A. (Universitat Autònoma de Barcelona. Departament de Medicina)
Alexandrov, Andrei V. (University of Tennessee Health Science Center)
Caso, Valeria (University of Perugia)
Shoamanesh, Ashkan (McMaster University/Population Health Research Institute (Canadà))
Sharma, Mukul (McMaster University/Population Health Research Institute (Canadà))
Tsivgoulis, Georgios (University of Tennessee Health Science Center)

Date:	2023
Abstract:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Ischemic stroke ; Stroke prevention ; Antithrombotic treatment ; Anticoagulation ; Factor Xia inhibitors ; Meta-analysis ; Randomized-controlled clinical trials
Published in:	Journal of clinical medicine, Vol. 12 (august 2023) , ISSN 2077-0383

DOI: 10.3390/jcm12175562
PMID: 37685629

15 p, 2.6 MB

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