Mini-reviews
Vol. 2 No. 3 (2023)
Factor XI inhibitors in adjunct to antiplatelet therapy: the ultimate dual-pathway inhibition?
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 3 August 2023
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A strategy of oral anticoagulants (OAC) in addition to single or dual antiplatelet therapy, known as dual-pathway inhibition (DPI), has shown to reduce thrombotic events in patients with cardiovascular disease. However, despite its efficacy, its use in clinical practice has been hindered by the fact this strategy is also associated with increased bleeding, including major bleeding. The use of low dose direct oral anticoagulant (i.e. rivaroxaban 2.5 mg twice daily) on top of antiplatelet therapy has been associated with reduced bleeding, but some safety concerns still exists. The availability of a novel class of OACs selectively targeting the intrinsic coagulation pathway and potentially uncoupling thrombosis and hemostasis has sparked the interest towards the use of a new generation DPI strategy associated with enhanced safety. Several phase II trials using factor XI (FXI) inhibitors on top of antiplatelet therapy in patients with coronary artery or cerebrovascular disease have been recently published and others are under investigation. We here discuss the available evidence and future perspectives of DPI with FXI inhibitors in patients with cardiovascular disease.
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Citations
Capodanno D, Bhatt DL, Eikelboom JW, et al. Dual-pathway inhibition for secondary and tertiary antithrombotic prevention in cardiovascular disease. Nat Rev Cardiol 2020;17:242-57. DOI: https://doi.org/10.1038/s41569-019-0314-y
Galli M, Franchi F, Rollini F, et al. Dual pathway inhibition in patients with atherosclerotic disease: pharmacodynamic considerations and clinical implications. Exp Rev Clin Pharmacol 2023;16:27-38. DOI: https://doi.org/10.1080/17512433.2023.2154651
Galli M, Capodanno D, Benenati S, et al. Efficacy and safety of dual-pathway inhibition in patients with cardiovascular disease: a meta-analysis of 49 802 patients from 7 randomized trials. Eur Heart J Cardiovasc Pharmacother 2022;8:519-28. DOI: https://doi.org/10.1093/ehjcvp/pvab043
Hsu C, Hutt E, Bloomfield DM, et al. Factor XI inhibition to uncouple thrombosis from hemostasis: JACC review topic of the week. J Am Coll Cardiol 2021;78:625-31. DOI: https://doi.org/10.1016/j.jacc.2021.06.010
Greco A, Laudani C, Spagnolo M, et al. Pharmacology and clinical development of factor XI inhibitors. Circulation 2023;147:897-913. DOI: https://doi.org/10.1161/CIRCULATIONAHA.122.062353
Prisco D, Mattioli I, De Caterina R, Bettiol A. The new era of anticoagulation: factor XI and XII inhibitors. Bleeding, Thrombosis, and Vascular Biology 2023;2:76. DOI: https://doi.org/10.4081/btvb.2023.76
De Caterina R, Prisco D, Eikelboom JW. Factor XI inhibitors: cardiovascular perspectives. Eur Heart J 2023;44:280-92. DOI: https://doi.org/10.1093/eurheartj/ehac464
Rao SV, Kirsch B, Bhatt DL, et al. A multicenter, phase 2, randomized, placebo-controlled, double-blind, parallel-group, dose-finding trial of the oral factor XIa inhibitor asundexian to prevent adverse cardiovascular outcomes after acute myocardial infarction. Circulation 2022;146:1196-206. DOI: https://doi.org/10.1161/CIR.0000000000001115
Shoamanesh A, Mundl H, Smith EE, et al. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet 2022;400:997-1007. DOI: https://doi.org/10.1016/S0140-6736(22)01588-4
Galli M, Laborante R, Ortega-Paz L, et al. Factor XI inhibitors in early clinical trials: a meta-analysis. Thromb Haemost 2023;123:576-84. DOI: https://doi.org/10.1055/a-2043-0346
Capodanno D, Angiolillo DJ. Timing, selection, modulation, and duration of P2Y(12) inhibitors for patients with acute coronary syndromes undergoing PCI. JACC Cardiovasc Intervent 2023;16:1-18. DOI: https://doi.org/10.1016/j.jcin.2022.10.023
Donadini MP, Ageno W. Milvexian and other drugs targeting Factor XI: a new era of anticoagulation? Bleeding, Thrombosis, and Vascular Biology 2022;1:22. DOI: https://doi.org/10.4081/btvb.2022.22
How to Cite
1.
Galli M, Gibson CM, Angiolillo DJ. Factor XI inhibitors in adjunct to antiplatelet therapy: the ultimate dual-pathway inhibition?. Bleeding Thromb Vascul Biol [Internet]. 2023 Aug. 3 [cited 2025 Sep. 5];2(3). Available from: https://www.btvb.org/btvb/article/view/90
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