Thromb Haemost 2023; 123(06): 576-584
DOI: 10.1055/a-2043-0346
Coagulation and Fibrinolysis

Factor XI Inhibitors in Early Clinical Trials: A Meta-analysis

1   Catholic University of the Sacred Heart, Rome, Italy
2   Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
,
Renzo Laborante
1   Catholic University of the Sacred Heart, Rome, Italy
,
Luis Ortega-Paz
3   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States
,
Francesco Franchi
3   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States
,
Fabiana Rollini
3   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States
,
Domenico D'Amario
4   Dipartimento Universitario di Medicina Traslazionale, Università Piemonte Orientale, Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara, Novara, Italy
,
5   Division of Cardiology, Azienda Ospedaliero Universitaria Policlinico “G. Rodolico-San Marco,” University of Catania, Catania, Italy
,
Elena Tremoli
2   Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy
,
Charles Micheal Gibson
6   Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
,
Roxana Mehran
7   Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, United States
,
3   Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States
› Institutsangaben
Funding None.


Abstract

Background Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes.

Methods We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy.

Results Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included. Compared with enoxaparin, FXI inhibitors were associated with reduced any-bleeding (risk ratio [RR]: 0.49, 95% confidence interval [CI]: 0.31–0.77), no difference in major bleeding (RR: 0.96, 95% CI: 0.41–2.28), and reduced trial-defined efficacy endpoint (RR: 0.62, 95% CI: 0.49–0.79), the latter driven by the high-dose regimens. Compared with DOACs, FXI inhibitors were associated with a trend toward reduced any-bleeding (RR: 0.66, 95% CI: 0.31–1.38) and no difference in major bleeding (RR: 1.03, 95% CI: 0.22–4.78) or in trial-defined efficacy endpoint (RR: 1.23, 95% CI: 0.88–1.70). Compared with placebo, FXI inhibitors were associated with increased any-bleeding (RR: 1.25, 95% CI: 1.08–1.43) and a trend toward increased major bleeding (RR: 1.21, 95% CI: 0.75–1.93), both driven by high-dose regimens, with no difference in trial-defined efficacy endpoint (RR: 1.02, 95% CI: 0.92–1.13).

Conclusion Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy.

Study registration This study is registered in PROSPERO (CRD42022367706).

Data Availability Statement

The data underlying this article are available in the article and in its online [Supplementary Material] (available in the online version).


Authors' Contribution

M.G. conceived and designed the study. M.G. and R.L. independently assessed studies for possible inclusion and collected the data. M.G. and R.L. analyzed the data. M.G. supervised the analysis. M.G. and D.J.A. drafted the manuscript. All authors revised and approved the final version of the manuscript.


Supplementary Material



Publikationsverlauf

Eingereicht: 24. Dezember 2022

Angenommen: 23. Februar 2023

Accepted Manuscript online:
25. Februar 2023

Artikel online veröffentlicht:
24. März 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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