Abstract 16612: Efficacy and Safety of Edoxaban for the Management of Elderly Patients With Atrial Fibrillation: Engage AF-TIMI 48
Background: Elderly patients with atrial fibrillation (AF) treated with anticoagulants are at higher risk of both ischemic and bleeding events compared to younger patients. Intracranial bleeding (ICH) remains one of the most concerning complications of anticoagulation therapy, and risk is strongly related to age. The ENGAGE AF-TIMI 48 trial showed that both the high (HD) and low dose (LD) regimens of the once daily oral factor Xa inhibitor edoxaban were non-inferior to well-managed warfarin (TTR 68.4%) in preventing stroke and systemic embolic events (SEE) while reducing major bleeding.
Methods: 21,105 patients were enrolled in ENGAGE-TIMI 48 trial and stratified into pre-specified age categories: <65 (n=5,497), 65 to 74 (n=7,134), ≥75 (n=8,474) years. The primary endpoints were stroke/SEE and major bleeding as defined by the ISTH and outcomes over 2.8 years of median follow-up compared by age and treatment.
Results: Regardless of treatment, the risk of major bleeding and stroke/SEE increased with age (p<0.001), but more markedly so for major bleeding. Both edoxaban regimens were similar to warfarin in effect on stroke/SEE across the age categories (HD vs. warfarin: <65yr HR 0.94, 65-74yr HR 0.89, ≥75yr HR 0.83; LD vs. warfarin: <65yr HR 1.42, 65-74yr HR 1.0, ≥75yr HR 1.12; P-int both NS). When comparing edoxaban with warfarin, a major impact was seen on absolute risk reduction for major bleeding, including ICH (figure). The edoxaban treatment benefits were consistent across ages (P-int NS for both).
Conclusion: The efficacy and safety of edoxaban compared to well-managed warfarin are consistent regardless of age in patients with AF. Due to the higher risk of bleeding with increasing age, the absolute benefits of edoxaban are greater in the elderly.
Author Disclosures: E. Toda Kato: None. R.P. Giugliano: Honoraria; Modest; Daiichi Sankyo, Merck. Consultant/Advisory Board; Modest; Amgen Inc., Daiichi Sankyo, Merck, Janssen. Research Grant; Significant; Amgen, Daiichi Sankyo, Merck. C.T. Ruff: Research Grant; Significant; Daiichi Sankyo. Honoraria; Significant; Daiichi Sankyo, Boehringer Ingelheim, Bristol-Meyers Squibb. Consultant/Advisory Board; Significant; Daiichi Sankyo, Boehringer Ingelheim, Bristol-Meyers Squibb. S.A. Murphy: Research Grant; Significant; Daiichi Sankyo. F. Nordio: None. T. Kimura: Employment; Significant; Daiichi Sankyo. J. Jin: Employment; Significant; Daiichi sankyo. H. Lanz: Employment; Significant; Daiichi Sankyo. M. Mercuri: Employment; Significant; Daiichi Sankyo. E. Braunwald: Research Grant; Significant; Daiichi Sankyo. Honoraria; Modest; Bayer. Other; Modest; Uncompensated participation in International Expert Advisory meeting with Daiichi Sankyo. E.M. Antman: None.
- © 2014 by American Heart Association, Inc.