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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/17/5562 |
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| author | Lina Palaiodimou Georgia Papagiannopoulou Aristeidis H. Katsanos Andreas Eleftheriou Theodore Karapanayiotides Panayiotis D. Mitsias Robin Lemmens Carlos A. Molina Andrei Alexandrov Valeria Caso Ashkan Shoamanesh Mukul Sharma Georgios Tsivgoulis |
| author_facet | Lina Palaiodimou Georgia Papagiannopoulou Aristeidis H. Katsanos Andreas Eleftheriou Theodore Karapanayiotides Panayiotis D. Mitsias Robin Lemmens Carlos A. Molina Andrei Alexandrov Valeria Caso Ashkan Shoamanesh Mukul Sharma Georgios Tsivgoulis |
| author_sort | Lina Palaiodimou |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T23:19:28Z |
| format | Article |
| id | doaj.art-656824d925d24d12b4c503057ce3df78 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T23:19:28Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-656824d925d24d12b4c503057ce3df782023-11-19T08:22:21ZengMDPI AGJournal of Clinical Medicine2077-03832023-08-011217556210.3390/jcm12175562Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-AnalysisLina Palaiodimou0Georgia Papagiannopoulou1Aristeidis H. Katsanos2Andreas Eleftheriou3Theodore Karapanayiotides4Panayiotis D. Mitsias5Robin Lemmens6Carlos A. Molina7Andrei Alexandrov8Valeria Caso9Ashkan Shoamanesh10Mukul Sharma11Georgios Tsivgoulis12Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, GreeceSecond Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, GreeceDivision of Neurology, McMaster University/Population Health Research Institute, Hamilton, ON L8L2X2, CanadaSecond Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, GreeceSecond Department of Neurology, School of Medicine, Faculty of Health Sciences, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, GreeceNeurology Department, University General Hospital of Heraklion, 71500 Heraklion, GreeceExperimental Neurology, Department of Neurosciences, Katholieke Universiteit Leuven, 3000 Leuven, BelgiumVall d’Hebron Stroke Center, Department of Neurology, Hospital Universitari Vall d’Hebron, Departament de Medicina, Universitat Autònoma de Barcelona, 08035 Barcelona, SpainDepartment of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USAStroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, 06129 Perugia, ItalyDivision of Neurology, McMaster University/Population Health Research Institute, Hamilton, ON L8L2X2, CanadaDivision of Neurology, McMaster University/Population Health Research Institute, Hamilton, ON L8L2X2, CanadaSecond Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, GreeceIntroduction: 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.https://www.mdpi.com/2077-0383/12/17/5562ischemic strokestroke preventionantithrombotic treatmentanticoagulationfactor Xia inhibitorsmeta-analysis |
| spellingShingle | Lina Palaiodimou Georgia Papagiannopoulou Aristeidis H. Katsanos Andreas Eleftheriou Theodore Karapanayiotides Panayiotis D. Mitsias Robin Lemmens Carlos A. Molina Andrei Alexandrov Valeria Caso Ashkan Shoamanesh Mukul Sharma Georgios Tsivgoulis Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis Journal of Clinical Medicine ischemic stroke stroke prevention antithrombotic treatment anticoagulation factor Xia inhibitors 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 | ischemic stroke stroke prevention antithrombotic treatment anticoagulation factor Xia inhibitors meta-analysis |
| url | https://www.mdpi.com/2077-0383/12/17/5562 |
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