Betrixaban for Extended Venous Thromboembolism Prophylaxis in High-Risk Hospitalized Patients: Putting the APEX Results into Practice

Abstract

Acutely ill hospitalized medical patients remain at high thromboembolic risk for several weeks after discharge. Previous trials with extended-duration thromboprophylaxis using enoxaparin, apixaban, and rivaroxaban failed to achieve acceptable net clinical benefit, largely due to excess of major bleeding. Betrixaban is a novel factor Xa inhibitor with unique pharmacokinetic properties, including low renal clearance, long half-life, and low peak-to-trough ratio. The phase III APEX trial (N\xa0=\xa07513) compared a betrixaban 160\xa0mg loading dose followed by 80\xa0mg once daily for 35–42\xa0days, with enoxaparin 40\xa0mg once daily for 6–14\xa0days; the betrixaban dose was reduced for renal impairment or a concomitant strong P-glycoprotein (P-gp) inhibitor. The primary efficacy endpoint of composite thrombotic events was not different between treatment arms in cohort 1 (d-dimer ≥\u20092\xa0×\xa0upper limit of normal). Subsequent exploratory analyses showed a statistically significant difference favoring betrixaban for symptomatic venous thromboembolism and net clinical benefit in the overall population. For the primary safety outcome, betrixaban did not significantly increase major bleeding compared with enoxaparin. Based on available data from the APEX trial and subanalyses, the use of betrixaban in patients similar to those enrolled in the APEX trial can reduce the risk of thromboembolic events without increasing the risk of major bleeding. Patients who may benefit more from betrixaban therapy include those with elevated d-dimer, history of venous thromboembolism, hospitalized for ischemic stroke, hospitalized for heart failure with N-terminal pro-B-type natriuretic peptide ≥\u20091975\xa0ng/L, or two or more VTE risk factors. Reduced-dose betrixaban does not appear to provide the same clinical utility as full-dose betrixaban.