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 = 7513) compared a
betrixaban 160 mg loading dose followed by 80 mg once daily for 35-42 days, with
enoxaparin 40 mg once daily for 6-14 days; 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 ≥ 2 × upper 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 ≥ 1975 ng/L, or two or more VTE risk factors. Reduced-dose
betrixaban does not appear to provide the same clinical utility as full-dose
betrixaban.