Edoxaban Versus Warfarin in Latin American Patients With Atrial Fibrillation: The ENGAGE AF-TIMI 48 Trial

J Am Coll Cardiol. 2018 Sep 25;72(13):1466-1475. doi: 10.1016/j.jacc.2018.07.037.

Abstract

Background: There is limited information about the use of antithrombotic therapies and outcomes of Latin American (LatAm) subjects with atrial fibrillation. The global ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial compared the efficacy and safety of edoxaban versus warfarin over a median follow-up of 2.8 years.

Objectives: The authors aimed to compare adjusted outcomes in Latin America versus outside Latin America and to compare outcomes stratified by anticoagulant treatment and region.

Methods: The authors analyzed clinical characteristics and outcomes, adjusted for baseline characteristics, the Human Development Index, and randomized treatment of 2,661 LatAm versus 18,444 non-Latin American subjects (nLAS).

Results: When compared with nLAS, LatAm subjects had a similar overall risk for stroke. After multivariate adjustment, the risks of stroke/systemic embolism (hazard ratio [HR]: 1.19; 95% confidence interval (CI): 0.96 to 1.47; p = 0.11) and major bleeding (HR: 1.10; 95% CI: 0.89 to 1.36; p = 0.39) were similar in LatAm and nLAS. LatAm subjects were at higher adjusted risk of death (HR: 1.48; 95% CI: 1.30 to 1.69; p < 0.001) and intracranial hemorrhage (ICH) (HR: 1.55; 95% CI: 1.00 to 2.41; p = 0.049). In both regions, when compared with warfarin, edoxaban reduced stroke/systemic embolism (HR: 0.64 and 0.91 in LatAm and nLAS, respectively), major bleeding (HR: 0.71 and 0.82), and cardiovascular death (HR: 0.78 and 0.88), without evidence of regional heterogeneity (pint = 0.41, 0.50, and 0.70, respectively). There was a greater reduction in hemorrhagic stroke with edoxaban in LatAm (HR: 0.16) than in nLAS (HR: 0.64; pint = 0.037).

Conclusions: After multivariable adjustment, LatAm subjects with atrial fibrillation had higher rates of intracranial hemorrhage and death than nLAS. Outcomes with higher-dose edoxaban versus warfarin were at least as favorable in LatAm subjects as in nLAS, with an even greater reduction in hemorrhagic stroke seen in LatAm.

Trial registration: ClinicalTrials.gov NCT00781391.

Keywords: Latin America; anticoagulation; atrial fibrillation; edoxaban.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Double-Blind Method
  • Embolism / epidemiology
  • Embolism / prevention & control
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Intracranial Hemorrhages / epidemiology
  • Latin America / epidemiology
  • Male
  • Myocardial Infarction / epidemiology
  • Pyridines / therapeutic use*
  • Stroke / epidemiology
  • Stroke / prevention & control
  • Thiazoles / therapeutic use*
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Pyridines
  • Thiazoles
  • Warfarin
  • edoxaban

Associated data

  • ClinicalTrials.gov/NCT00781391