Modification of outcomes with aspirin or apixaban in relation to CHADS(2) and CHA(2)DS(2)-VASc scores in patients with atrial fibrillation: a secondary analysis of the AVERROES study

Circ Arrhythm Electrophysiol. 2013 Feb;6(1):31-8. doi: 10.1161/CIRCEP.112.975847. Epub 2013 Feb 6.


Background: The impact of apixaban versus aspirin on ischemic stroke and major bleeding in relation to the CHADS(2) and CHA(2)DS(2)-VASc stroke risk scores in atrial fibrillation has not been investigated.

Methods and results: In this secondary analysis of the AVERROES trial, our principal objective was to assess the effect of treatment with aspirin or apixaban on ischemic stroke and major bleeding, in relation to the CHADS(2)/CHA(2)DS(2)-VASc scores. We found no significant heterogeneity for treatment efficacy on ischemic stroke for apixaban when subdivided by stroke risk strata, based on CHADS(2)/CHA(2)DS(2)-VASc. Effects were consistent irrespective of baseline risk, and thus, absolute benefits were greatest in the high-risk groups. There was also no significant heterogeneity for apixaban versus aspirin with regard to major bleeding, when subdivided by CHADS(2)/CHA(2)DS(2)-VASc scores. In multivariable analysis, significant predictors of stroke on aspirin were age ≥75 years, prior stroke or transient ischemic attack, estimated glomerular filtration rate <60 mL/min, and nonparoxysmal atrial fibrillation. Proportions of the study cohort classified as low/moderate/high risk using the CHADS(2) and CHA(2)DS(2)-VASc scores were 0.3%/71.7%/28.1% and <0.1%/10.5%/89.5%, respectively.

Conclusions: In an atrial fibrillation population, apixaban was superior to aspirin for stroke prevention, with similar rates of major bleeding, in the presence of one or more stroke risk factors, with consistency of the treatment effect by CHADS(2)/CHA(2)DS(2)-VASc scores.

Trial registration: NCT00496769.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Brain Ischemia / diagnosis
  • Brain Ischemia / etiology
  • Brain Ischemia / prevention & control*
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Health Status Indicators*
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyridones / adverse effects
  • Pyridones / therapeutic use*
  • Risk Assessment
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / etiology
  • Stroke / prevention & control*
  • Treatment Outcome


  • Fibrinolytic Agents
  • Pyrazoles
  • Pyridones
  • apixaban
  • Aspirin

Associated data