Abstract 19325: Betrixaban Reduces the Burden of Multiple Symptomatic Venous Thromboembolic Events in the APEX Trial

Introduction: Subjects enrolled in clinical trials may sustain multiple events, and the burden of disease is not accounted for in a time-to-first-event analysis. In the phase 3 APEX trial, we evaluated whether the incidence of all symptomatic venous thromboembolic events (VTE), including those that occur after the first event, would be reduced by extended-duration betrixaban versus standard-duration of enoxaparin. Methods: Hospitalized medically ill subjects were randomized in a double blind fashion to either extended-duration oral betrixaban (35 days) vs. standard-duration subcutaneous enoxaparin (10 ± 4 days) (n=7,513). Pre-specified symptomatic events included symptomatic deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and VTE-related death. All events were adjudicated by an independent committee and were assessed through the end of the active treatment phase (through day 42) and through the last patient contact. Analyses were performed in 3 progressively larger, inclusive cohorts: cohort 1 = local D-dimer ≥ 2 x upper limit of normal (ULN); cohort 2 = local D-dimer ≥ 2 x ULN or age ≥ 75 years; and all patients. A time-to-multiple-event analysis was performed using the Wei, Lin, and Weissfeld (WLW) method, which accounts for the correlation of multiple events within each patient. Results: Among 7,441 subjects, extended-duration betrixaban was associated with a significant 31% to 48% relative risk reduction in the risk of multiple VTE events through last subject contact as compared with standard-duration enoxaparin (Table 1). Through the entire trial duration, the number of patients with multiple events tended to be lower in the betrixaban arm as compared with the enoxaparin arm (1 patient vs. 6 patients, p=0.07). Conclusions: Extended-duration betrixaban reduces not only the first but also the total number of symptomatic venous thromboembolic events versus standard-dose enoxaparin among hospitalized medically ill patients.