This was a subgroup analysis of the ENGAGE AF-TIMI 48 trial in which 21,105 atrial fibrillation patients at moderate-to-high risk of stroke were randomised to once-daily edoxaban 30mg (low-dose) or high-dose (60mg) vs. warfarin. Patients were followed for a median of 2.8 years, and the primary efficacy endpoint experience was defined as >60 consecutive days exposure to VKA. Lower-dose edoxaban was reported to be similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73–1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08–1.60; P = 0.019). Compared to warfarin, the higher-dose edoxaban regimen reduced major bleeding by 20% (2.88 vs. 3.64% per year) in patients who were VKA naive and by 19% (2.85 vs. 3.54% per year) in those who were VKA experienced (P = 0.90). The lower-dose edoxaban regimen reduced major bleeding by 51% (1.80 vs. 3.64% per year) in patients who were VKA naive and by 48% (1.84 vs. 3.54% per year) in those who were VKA experienced (P = 0.71).
Edoxaban is an oral, once-daily factor Xa inhibitor. It has already been approved in the US to reduce risk of stroke and SE in patients with AF not caused by a heart valve problem. A marketing authorisation application has also been filed in the EU.