Symptomatic event reduction with extended-duration betrixaban in acute medically ill hospitalized patients.

Overview

abstract

BACKGROUND: Approximately 15%-30% of patients in trials of medical thromboprophylaxis will have missing compression ultrasound (CUS) data. The goal of the present analysis was to perform analyses to minimize missing data. METHODS: The APEX trial randomized 7,513 acutely medically ill hospitalized patients to thromboprophylaxis with either betrixaban for 35-42 days or enoxaparin for 6-14 days. A modified intent-to-treat (mITT) analysis was performed and included all subjects administered study drug, irrespective of CUS performance, and an analysis of symptomatic events which do not require performance of a CUS (symptomatic deep vein thrombosis, nonfatal pulmonary embolism, and venous thromboembolism (VTE)-related mortality). RESULTS: In the mITT population, betrixaban significantly reduced the primary end point (which included both symptomatic and CUS events) (165 [4.4%] vs 223 [6.0%]; relative risk = 0.75; 95% CI 0.61-0.91; P = .003; absolute risk reduction [ARR] = 1.6%; number needed to treat [NNT] = 63). Betrixaban also reduced symptomatic VTE through day 42 (35 [1.28%] vs 54 [1.88%], hazard ratio [HR] = 0.65; 95% CI 0.42-0.99; P = .044; ARR = 0.6%; NNT=167) as well as through day 77 (37 [1.02%] vs 67 [1.89%]; HR= 0.55; 95% CI 0.37-0.83; P = .003; ARR = 0.87%; NNT=115) as well as the individual end point of nonfatal pulmonary embolism (9 [0.25%] vs 20 [0.55%]; HR= 0.45; 95% CI 0.21-0.99; P = .041; ARR = 0.30%; NNT=334). On an "as-treated" basis, 80 mg of betrixaban reduced VTE-related mortality through day 77 (10 [0.34%] vs. 22 [0.79%]; HR=0.46; 95% CI 0.22-0.96; P = .035; ARR = 0.45%; NNT=223). CONCLUSION: In an mITT analysis of all patients administered study drug, extended-duration betrixaban reduced the primary end point as well as symptomatic events. In an as-treated analysis, 80 mg of betrixaban reduced VTE-related death.