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

Study Questions:

What is the effect of treatment with aspirin or apixaban on ischemic stroke, in relation to CHADS2 and the CHA2DS2-VASc scores?


In this secondary analysis of the AVERROES trial, the 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. Hazard ratios for the effect of treatment with apixaban versus aspirin according to CHADS2 and CHA2DS2-VASc risk category were estimated using separate Cox proportional hazards regression models fitted within each category.


The investigators 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 (AF). 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.


The authors concluded that in an AF population, apixaban was superior to aspirin for stroke prevention, in the presence of one or more stroke risk factors.


The primary observation from this study is that apixaban was superior to aspirin, irrespective of stroke risk strata (as assessed by CHADS2 and CHA2DS2-VASc scores). Given the broad range of patients studied in the AVERROES trial, and given the similar rates of major bleeding and its superior efficacy, apixaban appears to be the treatment choice in AF patients with one or more stroke risk factors, instead of aspirin. However, it should be noted that patients were entered into AVERROES on the basis of ineligibility or refusal to take vitamin K antagonist, and thus, these data may not be generalizable to all patients with AF.

Clinical Topics: Arrhythmias and Clinical EP, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Vitamin K, Stroke, Ischemic Attack, Transient, Pyrazoles, Risk Factors, Treatment Outcome, Proportional Hazards Models, Biological Markers, Glomerular Filtration Rate, Atrial Fibrillation, Pyridones

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