In a randomized, double-blind international study, edoxaban, a factor Xa inhibitor, was found to be comparable to warfarin in  efficacy in patients with acute venous thromboembolism (VTE), pulmonary embolism (PE) or both. The findings were presented Sept. 1 at the European Society of Cardiology Congress 2013 in Amsterdam and simultaneously published in The New England Journal of Medicine.

The Hokusai-VTE trial compared edoxaban (Daiichi-Sankyo) to warfarin in more than 8,000 patients from 37 countries between 2010 and 2012.

“The standard treatment [of VTE] consists of low-molecular-weight heparin followed by vitamin K antagonists,” wrote the researchers, led by Harry R. Buller, MD, of the University of Amsterdam. “A number of studies have established that new oral anticoagulants with or without initial heparin therapy are effective alternatives.”

All trial patients suffered VTE and were at first treated with heparin. They were randomly assigned to receive a once-daily dose of either edoxaban or warfarin. They continued on the medications between three and 12 months. Their main safety outcome was major or clinically relevant nonmajor bleeding and their main efficacy endpoint was recurrent symptomatic VTE.

The two drugs yielded similar results among the trial’s participants. In the edoxaban group, 3.2 percent of patients experienced another VTE during the study period compared with 3.5 percent of the patients in the warfarin group.

Patients in the edoxaban group experienced less bleeding, however. Among the edoxaban patients, 8.5 percent experienced the type of bleeding defined as the safety outcome compared with 10.3 percent of the warfarin group.

"In analyses of safety, the results were consistent with respect to both major bleeding and clinically relevant nonmajor bleeding, with fewer fatal and intracranial bleeds in the edoxaban group …, although the between-group difference with respect to major bleeding did not reach statistical significance," they wrote.

Of the subgroup of patients with PE, 938 had right ventricular dysfunction. Recurrent VTE occurred in 3.3 percent of the edoxaban patients and in 6.2 percent of the warfarin patients.

“[T]he Hokusai-VTE study showed that in a broad spectrum of patients with venous thromboembolism, including those with severe pulmonary embolism, edoxaban administered once daily after initial heparin was noninferior to standard therapy with warfarin after initial heparin, with significantly less bleeding,” the authors wrote.

The Hokusai-VTE trial was funded by Daiichi-Sankyo.