Extended prophylaxis of venous thromboembolism with betrixaban in acutely ill medical patients with and without cancer: insights from the APEX trial
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Acutely ill medical patients with cancer are at increased risk of venous thromboembolism (VTE). Thromboprophylaxis is recommended in the presence of cancer, but its safety is not known. The aim of this study was to assess the efficacy and safety of extended prophylaxis with betrixaban in cancer patients enrolled in the APEX trial. APEX was a randomized, double-blind trial comparing oral betrixaban 80 mg qd administered for 35–42 days with subcutaneous enoxaparin 40 mg qd administered for 10 ± 4 days. Patients with acute medical illness and a history of cancer or active cancer were eligible for inclusion. Primary efficacy outcome was VTE (composite of symptomatic VTE and asymptomatic proximal deep vein thrombosis); primary safety outcome was major bleeding. Of 7513 patients enrolled in the APEX trial, 959 patients (12.8%), 499 randomized to betrixaban and 460 to enoxaparin, had cancer. The primary efficacy outcome occurred in 5.7% of cancer patients treated with betrixaban and in 6.2% treated with enoxaparin (p = 0.95). No significant interaction according to the presence or absence of cancer was observed (p = 0.36). Major bleeding events occurred in 0.8% of patients in the betrixaban group and in 0% in the enoxaparin group (p = 0.13), with no significant interaction (p = 0.07). The composite of major and clinically relevant non-major bleeds was similar between the two groups (2.9% and 2.0%, respectively, RR 1.43, 95% CI 0.63–3.27). Betrixaban was similarly effective in the reduction of VTE among subjects with and without cancer. The incidence of major bleeding was similarly low.
KeywordsCancer Venous thromboembolism Medical patients Prophylaxis Betrixaban
Compliance with ethical standards
The APEX study was funded by Portola Pharmaceuticals. Megan K. Yee, Adrian Hernandez, Russell Hull, Samuel Z. Goldhaber, C Michael Gibson, and Alexander T Cohen have received grant support from Portola Pharmaceuticals. In addition, Walter Ageno has received grant support from Bayer and honoraria from Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Janssen, Portola, Sanofi, Aspen; Renato D. Lopes has received honoraria from Bayer, Boehringer Ingelheim, BMS, Pfizer, Daiichi Sankyo, Portola, Sanofi, Glaxo Smith Kline, Medtronic, Merck; Russell Hull has received honoraria from Sanofi; Adrian Hernandez has received honoraria from BMS, Pfizer, Astra Zeneca; C. Michael Gibson has received grants from Angel Medical Corporation, Bayer, CSL Behring, Janssen, Johnson and Johnson and honoraria from Angel Medical Corporation, Bayer, CSL Behring, Janssen, Johnson and Johnson, The Medicines Company, Boston Clinical Research Institute, Cardiovascular Research Foundation, Eli Lilly, Gilead Sciences, Novo Nordisk, Web MD, UpToDate in Cardiovascular Medicine, Amarin Pharma, Amgen, Boehringer Ingelheim, Chiesi, Merck, PharmaMar, Sanofi, Somahlution, St. Francis Hospital, Verreseon Corporation, Boston Scientific, Duke Clinical Research Institute, Impact Bio, Medimmune, Medtelligence, Microport, PERT Consortium; Alexander T Cohen has received grant support from BMS, Daiichi Sankyo, Pfizer and honoraria from BMS, Daiichi Sankyo, Pfizer, ONO.
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