Modification of Outcomes With Aspirin or Apixaban in Relation to CHADS2 and CHA2DS2-VASc Scores in Patients With Atrial Fibrillation: A Secondary Analysis of the AVERROES Study

Background—The impact of apixaban versus aspirin on ischemic stroke and major bleeding in relation to the CHADS2 and CHA2DS2-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 CHADS2/CHA2DS2-VASc scores. We found no significant heterogeneity for treatment efficacy on ischemic stroke for apixaban when subdivided by stroke risk strata, based on CHADS2/CHA2DS2-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 CHADS2/CHA2DS2-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 CHADS2 and CHA2DS2-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 CHADS2/CHA2DS2-VASc scores.