Edoxaban 15 mg in AF patients ≥80 reduced major bleeding by 49% (HR 0.34 vs warfarin) and had similar stroke risks compared to 30 mg dose.
Does edoxaban 15 mg reduce bleeding events without increasing stroke risk compared to edoxaban 30 mg in patients ≥80 years with atrial fibrillation and dose-reduction criteria?
In very elderly patients with atrial fibrillation meeting dose-reduction criteria, edoxaban 15 mg reduces major bleeding compared to 30 mg with comparable overall stroke/systemic embolism rates, though with a trend toward more ischemic strokes.
Absolute Event Rate: 0% vs 0%
Abstract Background Edoxaban is at least as effective as warfarin in preventing embolic and bleeding events in patients with atrial fibrillation (AF), but determining the optimal dose for individual patients can be challenging. Although current criteria for edoxaban dose reduction (from 60 to 30 mg) do not take age into account, older adults are known to have altered pharmacodynamics and a higher risk of bleeding. Thus, it remains unclear whether patients with both advanced age and standard dose-reduction criteria might benefit from an even lower dose of edoxaban. Purpose To evaluate ischemic and bleeding outcomes in very elderly patients (≥80 years) with AF and dose-reduction criteria receiving edoxaban 15 mg or 30 mg. Methods ENGAGE AF–TIMI 48 was a double-blind, multinational trial that randomized 21,105 patients with AF to one of two edoxaban regimens or warfarin. Overall, 3591 patients (17%) were ≥80 years; the 80-year cutoff for this analysis was based on the dose-reduction criteria for apixaban and previous studies. Per protocol, patients meeting at least one dose-reduction criterion (creatinine clearance ≤50 mL/min, weight ≤60 kg, or concomitant use of strong P-glycoprotein inhibitors) received a 50% reduced edoxaban dose, resulting in 15 mg or 30 mg. In this post-hoc analysis, we compared outcomes in 1891 patients ≥80 years who met dose-reduction criteria and received edoxaban 15 mg, 30 mg, or warfarin (Figure 1). Results Baseline characteristics were similar between the randomized groups. The median age was 83 years (IQR 81–85), 1,057 (56%) were women, and 1727 (91%) had a CHA2DS2-VASc score ≥4. In patients randomized to edoxaban, the most common criterion for dose-reduction was CrCl ≤50 mL/min, present in 1137 (91%) patients. There were no significant differences between edoxaban 15 mg and 30 mg for the primary endpoint of stroke or systemic embolism (Figure 2). Edoxaban 15 mg significantly reduced major bleeding events, particularly intracranial hemorrhage, compared with edoxaban 30 mg. There was a trend toward a higher rate of ischemic stroke in patients receiving edoxaban 15 mg. No significant differences between the two doses were observed for the endpoints of all-cause death or the primary net clinical outcome. In a secondary analysis, rates of stroke or systemic embolism were not significantly different between each edoxaban dose vs. warfarin (edoxaban 15 mg vs. warfarin, HR 0.97, 95% CI 0.67–1.42; edoxaban 30 mg vs. warfarin, HR 0.87, 95% CI 0.58–1.28). Compared with warfarin, major bleeding events were significantly lower with edoxaban 15 mg (HR 0.34, 95% CI 0.21–0.53) and edoxaban 30 mg (HR 0.66, 95% CI 0.45–0.95). Conclusion In a randomized comparison of AF patients ≥80 years meeting dose-reduction criteria, once daily edoxaban 15 mg resulted in comparable rates of stroke or systemic embolism relative to 30 mg, with significantly fewer major and intracranial bleeding events and a trend toward more ischemic strokes.
Zimerman et al. (Sat,) reported a other. Edoxaban 15 mg in AF patients ≥80 reduced major bleeding by 49% (HR 0.34 vs warfarin) and had similar stroke risks compared to 30 mg dose.