Edoxaban vs. Warfarin in Vitamin K antagonist experienced and naive patients with atrial fibrillation

Michelle L. O'Donoghue, Christian T. Ruff, Robert P. Giugliano, Sabina A. Murphy, Laura T. Grip, Michele F. Mercuri, Howard Rutman, Minggao Shi, Grzegorz Kania, Ondrej Cermak, Eugene Braunwald, Elliott M. Antman

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42 Scopus citations


Aims Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs).We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced. Methods and results ENGAGEAF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy end point was stroke or SEE.As a pre-specified subgroup, we analysed outcomes for those with or without prior VKA experience (>60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56-0.90] and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82-1.24; P interaction = 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73-1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08-1.60; P interaction = 0.019). Both higher-dose and lower-dose edoxaban regimens significantly reduced the risk of major bleeding regardless of prior VKA experience (P interaction = 0.90 and 0.71, respectively). Conclusion In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure.

Original languageEnglish
Pages (from-to)1470-1477
Number of pages8
JournalEuropean Heart Journal
Issue number23
StatePublished - 14 Jun 2015
Externally publishedYes


  • Atrial fibrillation
  • Edoxaban
  • Novel oral anticoagulant
  • Warfarin


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