P1732Extended duration betrixaban in acutely ill medical patients is associated with reduction in fatal or irreversible ischemic or bleeding events compared with standard dose enoxaparin: an APEX substudy

Abstract

Background: Among acutely ill medical patients, extended duration betrixaban showed a significant reduction in venous thromboembolism in the extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients (APEX) trial. Given the variable clinical impact of some efficacy and safety events, one approach to assess net clinical outcomes is to include only events that are either fatal or cause irreversible harm. Methods: This was a post-hoc analysis of the APEX trial, a multicenter, randomized, double-blind, placebo-controlled trial that randomized 7,513 hospitalized acutely ill medical patients to extended duration betrixaban vs. standard of care enoxaparin. Net clinical outcomes were evaluated as a composite of all fatal or irreversible safety and efficacy events in a time-to-first event analysis. Safety events included fatal bleeding or intracranial hemorrhage, and efficacy events included cardiopulmonary death (venous thromboembolism and cardiac), myocardial infarction, pulmonary embolism, and ischemic stroke. Findings: In D-Dimer + patients, betrixaban reduced fatal or irreversible events at 35-42 days (4.80% vs 3.54%, HR=0.73, ARR 1.26%, NNT 79, p=0.033) and at study end at 77 days (6.27% vs 4.36%, HR=0.70, ARR 1.91%, NNT52, p=0.005) vs enoxaparin. In all patients, betrixaban was associated with a significant reduction in fatal or irreversible events at 35-42 days (4.08% vs 2.90%, HR = 0.71, ARR 1.18%, NNT=86, p=0.006) as well as through the end of the study follow-up (5.17% vs 3.64%, HR=0.70, ARR 1.53%, NNT 65, p=0.002) (Figure). Interpretation: Among hospitalized medically ill patients, extended duration betrixaban demonstrates a favorable net clinical outcome and is associated with an approximate 30% reduction in fatal or irreversible ischemic or bleeding events compared with standard duration enoxaparin followed by placebo. 65 patients would require treatment with betrixaban to prevent one fatal or irreversible event vs enoxaparin. (Figure Presented).