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Betrixaban is a direct factor Xa inhibitor with a renal excretion of only approximately 5-7%. On June 23rd 2017, it became the first direct oral anticoagulant to receive Food and Drug Administration approval for the prevention of venous thromboembolism in acutely ill medical patients, and the first anticoagulant agent to be approved for extended-duration thromboprophylaxis after hospital discharge in this setting. Approval followed the results of the APEX trial, a phase III clinical trial comparing betrixaban (80 mg) administered for 35-42 days with enoxaparin (40 mg) administered for 10 ± 4 days. This study for the first time applied a risk assessment model, integrating clinical factors and a laboratory marker to identify high risk patients. To improve safety, a dose reduction was used for patients with creatinine clearance between 15 and 30 mL/min (betrixaban 40 mg and enoxaparin 20 mg) and for patients receiving concomitant treatment with potent P-glycoprotein inhibitors (betrixaban 40 mg). The primary prespecified analysis tested the hypothesis that the benefit of extended thromboprophylaxis with betrixaban was greatest in patients with elevated D-dimer, but the 21% relative risk reduction failed to meet the prespecified threshold for statistical significance. However, the analysis of the overall study population showed a favorable net clinical benefit with betrixaban, with a statistically significant reduction in all efficacy outcomes and no increase in major bleeding rates. An ongoing trial, MARINER, is also assessing a combined approach for risk stratification comparing extended-duration rivaroxaban with standard duration low molecular weight heparin.
PMID: 28808888 [PubMed - as supplied by publisher]