Edoxaban vs Dalteparin in Cancer-Associated Venous Thromboembolism
In the phase III Hokusai VTE Cancer trial reported by Raskob et al in The New England Journal of Medicine, the direct-acting oral factor Xa inhibitor edoxaban proved noninferior to the low–molecular-weight heparin dalteparin in the composite outcome of recurrent venous thromboembolism or major bleeding among cancer patients with acute symptomatic or incidental venous thromboembolism.
Study Details
In the open-label noninferiority trial, 1,046 patients from 114 sites in 13 countries were randomized between July 2015 and December 2016 to receive low–molecular-weight heparin for at least 5 days followed by oral edoxaban at 60 mg once daily (n = 522) or subcutaneous dalteparin at 200 IU/kg once daily for 1 month followed by 150 IU/kg once daily (n = 524). Treatment was given for at least 6 months and up to 12 months. The primary outcome was the composite of recurrent venous thromboembolism or major bleeding during 12 months after randomization, irrespective of treatment duration. The noninferiority threshold was specified as a hazard ratio (HR) upper limit of the 95% confidence interval (CI) of < 1.5 with a two-sided alpha level of 0.05.
The median duration of assigned treatment was 211 days (interquartile range = 76–357 days) in the edoxaban group and 184 days (interquartile range = 85–341 days) in the dalteparin group (P = .01). A primary-outcome event occurred in 67 patients in the edoxaban group (12.8%) vs 71 patients (13.5%) in the dalteparin group (HR = 0.97, 95% CI = 0.70–1.36, P = .006 for noninferiority; P = 0.87 for superiority). Recurrent venous thromboembolism occurred in 7.9% vs 11.3% of patients (difference in risk = -3.4 percentage points, 95% CI = -7.0–0.2 percentage points). Major bleeding occurred in 6.9% vs 4.0% (difference in risk = 2.9 percentage points, 95% CI = 0.1–5.6 percentage points).
The investigators concluded, “Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin.”
The study was funded by Daiichi Sankyo.
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