PURPOSE: To assess the efficacy and safety of betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients.METHODS: The APEX trial randomized 7513 acutely ill hospitalized patients to betrixaban for 35-42days or enoxaparin for 10±4days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35-42days and at 77days.RESULTS: At 35-42days, extended betrixaban reduced the risk of VTE (4.27% vs 7.95%, P=0.042) without causing excess major bleeding (1.14% vs 3.13%, P=0.07). Both VTE (3.32% vs 8.33%, P=0.013) and major bleeding (0.00% vs 3.26%, P=0.003) were decreased in the full-dose stratum. Patients who received betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P=0.011; full-dose stratum: 3.32% vs 0.36%, P=0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P=0.30; full-dose stratum: 13.65% vs 16.30%, P=0.39).CONCLUSIONS: Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration betrixaban had fewer VTE without more major bleeding events. The benefit of betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies.CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.
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