Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the factor Xa (FXa) inhibitor betrixaban for extended-duration prophylaxis of acute medically ill patients with venous thromboembolism (VTE) risk factors.
Data sources: A MEDLINE/PubMed (January 1990 to October 2017) search was conducted using the following keywords: betrixaban, PRT054021, FXa inhibitor, novel oral anticoagulant, NOAC, direct oral anticoagulant, DOAC, and target specific oral anticoagulant, TSOAC. References of identified articles were searched by hand for additional relevant citations.
Study selection and data extraction: We included English-language articles evaluating betrixaban pharmacology, pharmacokinetics, efficacy, or safety in human subjects for VTE prophylaxis.
Data synthesis: Betrixaban is a FXa inhibitor that decreases prothrombinase activity and thrombin generation. Betrixaban efficacy and safety has been compared with that of enoxaparin for prophylaxis of VTE in acutely ill medical patients. In the APEX trial and substudies, extended-duration betrixaban was superior in efficacy to standard-duration enoxaparin in patients at high risk for VTE, including those with elevated D-dimer levels (≥2× upper limit of normal) and of older age (≥75 years). Betrixaban is noninferior to enoxaparin in rates of major bleeding, but the former is associated with more clinically relevant nonmajor bleeding events.
Conclusion: Betrixaban is the first oral agent approved for extended-duration VTE prophylaxis in acutely ill hospitalized patients. Extended-duration thromboprophylaxis with betrixaban reduces the risk of VTE compared with standard-duration thromboprophylaxis with enoxaparin but is associated with increased risk of bleeding.
Keywords: PRT054021; anticoagulant; betrixaban; factor Xa inhibitors; pharmacology; thromboprophylaxis; venous thromboembolism.