4.7 Article

Clinical Pharmacology of Factor XI Inhibitors: New Therapeutic Approaches for Prevention of Venous and Arterial Thrombotic Disorders

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JOURNAL OF CLINICAL MEDICINE
卷 11, 期 21, 页码 -

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MDPI
DOI: 10.3390/jcm11216314

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anticoagulation; venous thromboembolism; atrial fibrillation; thrombosis; bleeding

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This review summarizes the clinical pharmacology and evidence from phase 2 clinical trials for drugs targeting FXI in the treatment and prevention of thrombosis, showing the potential effectiveness of FXI inhibitors without impairing hemostasis.
Bleeding is the dominant adverse event of anticoagulation and often discourages many patients and physicians from starting treatment with anticoagulant drugs. The fact that factor (F)XI deficiency is associated with a mild bleeding phenotype and that FXI knockdown or inhibition in different animal models reduced the occurrence of thrombotic events in response to injury suggests that FXI is more important for the coagulation propagation and thrombotic process than for the overall hemostasis. The aim of this review is to summarize clinical pharmacology and evidence from phase 2 clinical trials on efficacy and safety of drugs directed against FXI for the treatment and prevention of thrombosis. Inhibition of FXI or FXIa has been proven to be effective in phase 2 studies at preventing venous thromboembolism (VTE) in patients undergoing total knee arthroplasty, or for prevention of major adverse vascular events in patients with end-stage kidney disease undergoing hemodialysis or as adjuncts to antiplatelet therapy for prevention of recurrent ischemic events in patients with acute myocardial infarction or non-cardioembolic stroke. Should the efficacy of FXI inhibitors as anticoagulant without impairing the hemostasis be proven in phase 3 randomized clinical trials, it would provide an innovative therapeutic option.

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