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

• Published in: The American heart journal 2018-04, Vol.198, p.84-90
• Main Authors: Gibson, C. Michael, Nafee, Tarek, Yee, Megan K., Chi, Gerald, Korjian, Serge, Daaboul, Yazan, AlKhalfan, Fahad, Kerneis, Mathieu, Goldhaber, Samuel Z., Hull, Russel, Hernandez, Adrian F., Cohen, Alexander T., Harrington, Robert A.
• Format: Article
• Language: English
• Subjects: Acute Disease; Aged; Aged, 80 and over; Anticoagulants - therapeutic use; Benzamides - therapeutic use; Clinical trials; Compression; Critical Illness - therapy; Data compression; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug dosages; Embolism; Female; Heart failure; Hospitalization; Humans; Incidence; Infectious diseases; Intention to Treat Analysis; Kaplan-Meier Estimate; Life Sciences; Male; Missing data; Mortality; Patients; Population; Primary Prevention - methods; Prognosis; Proportional Hazards Models; Pulmonary Embolism - epidemiology; Pulmonary Embolism - prevention & control; Pyridines - therapeutic use; Reduction; Risk Assessment; Survival Analysis; Thromboembolism; Thrombosis; Treatment Outcome; Ultrasound; Venous Thromboembolism - epidemiology; Venous Thromboembolism - prevention & control
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2017.12.015

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. 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). 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). 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.