Abstract 11748: Edoxaban versus Warfarin in Patients at Increased Risk of Falling - A Subgroup Analysis of the ENGAGE AF-TIMI 48 Trial
Background: Patients at an increased risk of falling are particularly at risk for undertreatment with oral anticoagulation. The current subgroup analysis assessed the relative efficacy and safety of edoxaban vs. warfarin in patients at increased risk of falling in the ENGAGE AF TIMI 48 study.
Methods & Results: Nine-hundred patients (4.3%) included in ENGAGE AF-TIMI 48 were judged to be at increased risk of falling by the investigator at randomization. These patients were older (median 77 years (IQR 72, 82) vs. 72 (64, 77); p <0.001), and had a higher prevalence of co-morbidities including prior stroke/TIA, diabetes and coronary artery disease. Patients at increased risk of falling demonstrated a higher risk for stroke or systemic embolism (2.68%/year vs. 1.77%/year, HR 1.51 (95% CI 1.17-1.96, p=0.002), major bleeding (4.72%/year vs. 2.67%/year, HR 1.74 (95% CI 1.39-2.18), p<0.001) and bone fractures (6.04%/year vs. 2.16%/year, HR 2.80 (95% CI 2.28-3.43), p<0.001). No treatment interaction was observed in patients at increased risk of falling, both for efficacy and safety endpoints, except for no fatal bleeds in patients with vs. without increased fall risk treated with edoxaban compared to warfarin. Due to the higher frequency of events, a larger absolute risk reduction was observed under edoxaban compared to warfarin in patients with vs. without increased risk of falling for intracranial hemorrhage and life threatening bleeding.
Conclusions: Patients at increased risk of falling are a high-risk subgroup, with an increased risk for both stroke/SEE as well as for bleeding. These patients demonstrate consistent efficacy and safety with edoxaban as compared to well-managed warfarin. The absolute risk of the most severe bleeding complications was higher in patients at increased risk of falling resulting in an even greater absolute risk reduction in these patients with edoxaban vs. warfarin.
Author Disclosures: J. Steffel: Ownership Interest; Modest; CorXL (co-president). Consultant/Advisory Board; Modest; Boston Scientific, Amgen, Astra Zeneca, Boehringer Ingelheim, Cook Medical, Sanofi-Aventis, Sorin, Zoll, Atricure. Research Grant; Significant; Bayer, Daiichi-Sankyo, Biotronik, Medtronic, St. Jude Medical. Consultant/Advisory Board; Significant; Bayer, Biotronik, Bristol-Myers Squibb, Daiichi-Sankyo, Medtronic, Pfizer, St. Jude Medical, Biosense Webster. R.P. Giugliano: Honoraria; Modest; Merck. Consultant/Advisory Board; Modest; Amgen, GlaxoSmithKline, Merck, Portola, American College of Cardiology, CVS Caremark. Other; Modest; St Jude Medical. Research Grant; Significant; Amgen, Merck. Other; Significant; Lexicon. E. Braunwald: Research Grant; Significant; Daiichi-Sankyo. S. Murphy: Research Grant; Significant; Daiichi-Sankyo. M. Mercuri: Employment; Significant; Daiichi-Sankyo. Other; Significant; pending patent related to the clinical properties of edoxaban. Y. Choi: Employment; Significant; Daiichi-Sankyo. E.M. Antman: None. C.T. Ruff: Research Grant; Modest; Astra Zeneca, Eisai, Intarcia. Research Grant; Significant; Daiichi-Sankyo. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Bayer, Portola. Consultant/Advisory Board; Significant; Daiichi Sankyo.
- © 2015 by American Heart Association, Inc.