Edoxaban Versus Warfarin in Atrial Fibrillation Patients at Risk of Falling: ENGAGE AF–TIMI 48 Analysis

Jan Steffel, Robert P. Giugliano, Eugene Braunwald, Sabina A. Murphy, Michele Mercuri, Youngsook Choi, Phil Aylward, Harvey White, Jose Luis Zamorano, Elliott M. Antman, Christian T. Ruff

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)


Background Anticoagulation is often avoided in patients with atrial fibrillation who are at an increased risk of falling. Objectives This study assessed the relative efficacy and safety of edoxaban versus warfarin in the ENGAGE AF–TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48) trial in patients with atrial fibrillation judged to be at increased risk of falling. Methods We performed a pre-specified analysis of the ENGAGE AF–TIMI 48, comparing patients with versus without increased risk of falling. Results Nine hundred patients (4.3%) were judged to be at increased risk of falling. These patients were older (median, 77 vs. 72 years; p < 0.001), and had a higher prevalence of comorbidities including prior stroke/transient ischemic attack, diabetes, and coronary artery disease. After multivariable adjustment, patients at increased risk of falling experienced more bone fractures caused by falling (adjusted hazard ratio [HRadj]: 1.88; 95% confidence interval [CI]: 1.49 to 2.38; p < 0.001), major bleeding (HRadj: 1.30; 95% CI: 1.04 to 1.64; p = 0.023), life-threatening bleeding (HRadj: 1.67; 95% CI: 1.11 to 2.50; p = 0.013), and all-cause death (HRadj: 1.45; 95% CI: 1.23 to 1.70; p < 0.001), but not ischemic events including stroke/systemic embolic event (HRadj: 1.16; 95% CI: 0.89 to 1.51; p = 0.27). No treatment interaction was observed between either dosing regimens of edoxaban and warfarin for the efficacy and safety outcomes. Treatment with edoxaban resulted in a greater absolute risk reduction in severe bleeding events and all-cause mortality compared with warfarin. Conclusions Edoxaban is an attractive alternative to warfarin in patients at increased risk of falling, because it is associated with an even greater absolute reduction in severe bleeding events and mortality. (Effective aNticaoGulation with factor xA next Generation in Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391)

Original languageEnglish
Pages (from-to)1169-1178
Number of pages10
JournalJournal of the American College of Cardiology
Issue number11
Publication statusPublished or Issued - 13 Sep 2016
Externally publishedYes


  • NOACs
  • anticoagulation
  • atrial fibrillation
  • edoxaban
  • falls
  • frailty

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this