Key result
Factor XI and XII inhibitors are emerging as promising new anticoagulants in phase 2 and 3 trials, potentially offering effective thromboprophylaxis with a lower risk of major bleeding.
Why the study?
Residual cardio- and cerebrovascular risk and major bleeding remain unmet medical needs with direct anticoagulants, prompting the review of factor XI and XII inhibitors.
Inhibition of the contact coagulation pathway via Factor XI and XII represents a promising new approach to anticoagulation that may address unmet needs in high-bleeding-risk patients.
Answers are grounded in this paper and cite their sources.
May reduce bleeding in thromboprophylaxis if confirmed; leaves open need for phase 3 safety and efficacy data.
The two last decades have witnessed a revolution in the field of anticoagulation, mainly due to the advent of direct anticoagulant with targeted action against single coagulation proteins. However, the residual risk of cardio- and cerebrovascular events, particularly in some critical settings, and the risk of major bleeding still represent unmet medical needs. Preclinical studies and experience from families with genetic deficiencies of factor XI or XII (FXI and FXII) allowed to identify these factors involved in the contact pathway of coagulation as potential targets for new anticoagulant approaches. To date, several pharmacological classes of FXI and FXII inhibitors have been developed, including antisense oligonucleotides, monoclonal antibodies, small molecules, natural inhibitors, and aptamers, and various molecules are currently under phase 2 or 3 clinical investigation. Particularly, promising results have been obtained in patients undergoing major orthopedic surgery, in those with end-stage kidney disease, atrial fibrillation and acute coronary syndrome. This review summarizes current knowledge on FXI and FXII inhibitors, with a particular focus on their pharmacological properties and potential clinical indications.
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Prisco et al. (2023) conducted a review in Thrombosis and bleeding disorders. Factor XI and XII inhibitors was evaluated. Factor XI and XII inhibitors are emerging as promising new anticoagulants in phase 2 and 3 trials, potentially offering effective thromboprophylaxis with a lower risk of major bleeding.
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