Efficacy and Safety of Edoxaban vs Warfarin in Patients With AF and Frailty

Takeaway

• Edoxaban was similarly efficacious to warfarin for stroke prevention across the frailty spectrum.
• Bleeding events were reduced in patients who received edoxaban, except in those with severe frailty.
• Overall, with increasing frailty, there was an increase in the risk of stroke and bleeding.

Why this matters

• Findings highlight the need for high-quality, frailty-specific population randomised controlled trials to guide therapy in this vulnerable population.

Study design

• Post hoc analysis of 20,867 patients with atrial fibrillation (AF) from the ENGAGE AF-TIMI 48 trial who were randomly (1:1:1) assigned to receive edoxaban 30 mg, edoxaban 60 mg or warfarin.
• Patients were categorised based on the frailty index into fit (n=4459), pre-frailty (n=12326), mild-moderate (n=3722) and severe frailty (n=360) groups.
• Primary efficacy outcome: stroke or systemic embolism; safety outcome: major bleeding.
• Funding: None disclosed.

Key results

• There was no difference in stroke or systemic embolism between the treatment arms, including when stratified by frailty category.
• On average over the follow-up period, for each 0.1 increase in the frailty index, the risk of stroke or systemic embolism increased by 37% (adjusted HR [aHR], 1.37; 95% CI, 1.19-1.58) and major bleeding by 42% (aHR, 1.42; 95% CI, 1.27-1.59).
• Bleeding events were 53% lower with edoxaban 30 mg vs warfarin (HR, 0.47; 95% CI, 0.40-0.54) and 21% lower with edoxaban 60 mg (HR, 0.79; 95% CI, 0.69-0.89).
• Edoxaban 30 mg vs warfarin reduced the risk of major bleeding in the fit (HR, 0.42; 95% CI, 0.28-0.62), pre-frailty (HR, 0.46; 95% CI, 0.38-0.56) and mild-moderate frailty groups (HR, 0.47; 95% CI, 0.35-0.64), but not in the severe frailty group (HR, 0.74; 95% CI, 0.36-1.52).
• Edoxaban 60 mg reduced the risk of major bleeding in the pre-frailty (HR, 0.76; 95% CI, 0.64-0.90) and mild-moderate frailty groups only (HR, 0.75; 95% CI, 0.57-0.98).

Limitations

• Post hoc analysis.

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.