Image by Andre E.X. Brown
Health Canada has approved edoxaban (Lixiana®), an oral factor Xa inhibitor, for use in patients with venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF).
The drug can now be used to treat and prevent the recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE).
It can also be used to prevent stroke and systemic embolism in adults with NVAF in whom anticoagulation is appropriate.
Edoxaban was discovered and developed by Daiichi Sankyo Co., Ltd., but Servier Canada will market the drug in Canada.
Edoxaban has been approved in the US, European Union, Switzerland, Japan, South Korea, Taiwan, and Hong Kong. The drug is marketed as Savaysa® in the US and as Lixiana® elsewhere.
Health Canada’s approval of edoxaban is based on data from a pair of phase 3 trials, ENGAGE AF-TIMI 48 and Hokusai-VTE.
Hokusai-VTE
In the Hokusai-VTE trial, researchers evaluated edoxaban in 4921 patients with DVT and 3319 with PE. Patients received initial treatment with low-molecular-weight heparin and were then randomized to receive edoxaban or warfarin daily for 3 to 12 months.
Overall, edoxaban proved as effective as warfarin. Recurrent, symptomatic VTE occurred in 3.2% and 3.5% of patients, respectively (P<0.001 for non-inferiority).
In addition, the incidence of clinically relevant bleeding was significantly lower in the edoxaban arm than the warfarin arm—8.5% and 10.3%, respectively (P=0.004 for superiority).
ENGAGE-AF TIMI 48
In the ENGAGE AF-TIMI 48 trial, researchers compared edoxaban and warfarin as prophylaxis for stroke or systemic embolism in patients with NVAF.
The trial included 21,105 patients who were randomized to receive warfarin (n=7036), edoxaban at 60 mg (n=7035), or edoxaban at 30 mg (n=7034).
Edoxaban was at least non-inferior to warfarin with regard to efficacy. The annual incidence of stroke or systemic embolism was 1.50% with warfarin, 1.18% with edoxaban at 60 mg (P<0.001 for non-inferiority), and 1.61% with edoxaban at 30 mg (P=0.005 for non-inferiority).
In addition, edoxaban was associated with a significantly lower rate of major and fatal bleeding. The annual incidence of major bleeding was 3.43% with warfarin, 2.75% with edoxaban at 60 mg (P<0.001), and 1.61% with edoxaban at 30 mg (P<0.001).
Fatal bleeds occurred at an annual rate of 0.38% with warfarin, 0.21% with edoxaban at 60 mg (P=0.006), and 0.13% with edoxaban at 30 mg (P<0.001).
