Effects of Regional Differences in Asia on Efficacy and Safety of Edoxaban Compared With Warfarin--Insights From the ENGAGE AF-TIMI 48 Trial.

BACKGROUND

In 21,105 patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial, edoxaban was non-inferior to warfarin in preventing thromboembolic events while reducing bleeding. We compared results in Japan with the rest of East Asia (EA), including China, Korea, and Taiwan.

METHODS AND

RESULTS

We compared baseline characteristics, time-in-therapeutic range (TTR) for warfarin, and outcomes (efficacy: stroke or systemic embolic events [SEE], safety: major bleeding). Interaction P values were used to assess for effect modification of treatment (higher-dose edoxaban [HDE, 60 mg/30 mg] vs. warfarin; lower-dose edoxaban [LDE, 30 mg/15 mg] vs. warfarin) by region with adjustments for baseline characteristics. Fewer patients in Japan (n=1,010) were female, taking aspirin or amiodarone, naïve to warfarin (P<0.001 for each), had a history of stroke or transient ischemic attack (P=0.02), and more patients needed dose reduction (P<0.001) compared with EA (n=933). The mean TTR was higher in Japan (70% vs. 56%, P<0.001). Evidence for statistical interactions was observed for HDE vs. warfarin by region for stroke/SEE (adjusted P-int=0.052) and major bleeding (adjusted P-int=0.048) with greater relative efficacy and safety with HDE in EA compared with Japan. No interactions were observed for LDE vs. warfarin after adjustment.

CONCLUSIONS

HDE had a greater relative efficacy and safety in EA compared with Japan that was only partially explained by differences in baseline characteristics and TTR.