Results from the Hokusai-VTE study presented at the European Society of Cardiology (ESC) congress have shown that the oral anticoagulant edoxaban was non-inferior to warfarin in the treatment of venous thromboembolism (VTE). The randomised trial also demonstrated that the new anticoagulant was safer than warfarin when either drug was used with initial low molecular weight heparin.
The study found that the investigational, oral, once-daily direct factor Xa-inhibitor edoxaban (Daiichi Sankyo) met the primary efficacy endpoint of non-inferiority compared to warfarin, following initial use of heparin in both arms, for the treatment and prevention of recurrent symptomatic venous thromboembolism. Once-daily edoxaban also demonstrated superiority compared to warfarin for the principal safety outcome of clinically relevant bleeding (the composite of major or clinically relevant non-major bleeding).
The results were presented by lead investigator Harry R Büller, Department of Vascular Medicine at Academic Medical Center in Amsterdam in a Hot Line session and published online simultaneously in the New England Journal of Medicine.
In the Hokusai-VTE study, patient specific dosing was applied according to the study protocol. Edoxaban was dosed at 60mg once-daily, except for those patients with clinical factors that commonly impact response to oral anticoagulants (renal impairment, low body weight, or concomitant use of certain p-glycoprotein inhibitors) who received edoxaban 30mg according to the study protocol.
The Hokusai-VTE study was designed to reflect clinical practice using a flexible treatment duration of three to 12 months, including initial heparin treatment, in a broad spectrum of venous thromboembolism patients, including those with severe pulmonary embolism. For the primary efficacy endpoint, edoxaban demonstrated non-inferiority with a numerically lower incidence of recurrent symptomatic venous thromboembolism compared to warfarin (3.2% vs. 3.5%, respectively) (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.70 to 1.13; p
The reduced dose of edoxaban was found to have an efficacy profile consistent with the overall study cohort, with fewer recurrent venous thromboembolism events in patients receiving 30mg edoxaban (n=733) compared to warfarin (n=719) (venous thromboembolism recurrence of 3% vs. 4.2%; HR, 0.73; 95% CI, 0.42 to 1.26). Clinically relevant bleeding in patients receiving edoxaban 30mg was significantly lower compared to warfarin (7.9% vs. 12.8%, respectively) (HR, 0.62; 95% CI, 0.44 to 0.86).
Among patients with deep vein thrombosis (n=4,921), venous thromboembolism recurrence was similar in the edoxaban and warfarin groups (3.4% vs. 3.3%, respectively) (HR, 1.02; 95% CI, 0.75 to 1.38), while the incidence of recurrent venous thromboembolism among patients with pulmonary embolism (n=3,319) was numerically lower for patients treated with once-daily edoxaban compared to warfarin (2.8% vs. 3.9%, respectively) (HR, 0.73; 95% CI, 0.50 to 1.06). Additionally, in a sub-group analysis, patients with severe pulmonary embolism and evidence of right ventricular dysfunction (defined as NT pro-BNP ≥500pg/mL, n=938) treated with edoxaban had a 48% lower risk of recurrent symptomatic venous thromboembolism compared to warfarin (3.3% vs. 6.2%, respectively) (HR, 0.52; 95% CI, 0.28 to 0.98).
“Hokusai-VTE was designed to include a broad range of venous thromboembolism patients, including those with severe pulmonary embolism, and we are therefore pleased that the study found that edoxaban administered once-daily is as efficacious as warfarin for the prevention of recurrent symptomatic venous thromboembolism while significantly reducing the risk of bleeding,” said Büller. “A promising finding was the sizeable reduction in recurrent symptomatic venous thromboembolism among patients with severe pulmonary embolism who were treated with edoxaban.”