The CHA2D2-VASc Score Identifies Those Patients With Atrial Fibrillation and a CHADS2 Score of 1 Who Are Unlikely to Benefit From Oral Anticoagulant Therapy

Study Questions:

Can the CHA2DS2-VASc score further discriminate which patients with atrial fibrillation and a CHADS2 score of 1 will benefit from antithrombotic treatment?


The authors reviewed data from the AVERROES and ACTIVE studies, selecting all patients with CHADS2 score 1 who were treated with either aspirin or aspirin plus clopidogrel, and calculating the incidence of stroke or systemic embolus according to the subjects’ CHA2DS2-VASc score. (The AVERROES study was a randomized trial of apixaban vs. aspirin in atrial fibrillation; the ACTIVE studies were randomized trials of either aspirin vs. aspirin plus clopidogrel, or aspirin plus clopidogrel vs. warfarin). The CHA2DS2-VASc score adds three additional risk factors to the CHADS2 score: age 65-74, female sex, and history of vascular disease (coronary artery disease [CAD] or peripheral arterial disease [PAD]). The outcome of interest for this analysis was the composite endpoint of ischemic or nonspecified stroke plus systemic embolus. The ability of the CHA2DS2-VASc score to further discriminate between high and low risk patients in this group of patients with a CHADS2 score of 1 was assessed with the Harrell’s c-statistic.


There were 4,670 patients with a baseline CHADS2 score of 1, among whom 26% a CHA2DS2-VASc score of 1 and 74% had a score of ≥2. The annual incidence of the composite embolic endpoint was 0.9% (95% confidence interval [CI], 0.6-1.3) and 2.1% (95% CI, 1.8-2.5) for a CHA2DS2-VASc score of 1 and ≥2, respectively, in a cumulative 11,414 patient-years of follow-up. The CHA2DS2-VASc score had a c-statistic of 0.587 (95% CI, 0.550-0.624). Among the additional risk factors in the CHA2DS2-VASc score, age 65-74 was the most potent risk factor (adjusted hazard ratio [HR], 1.90; 95% CI, 1.38-2.64), followed by female sex (HR, 1.32; 95% CI, 1.00-1.75). In this analysis, history of CAD or PAD was not independently associated with increased embolic risk (HR, 0.97; 95% CI, 0.65-1.41).


The authors concluded that the CHA2DS2-VASc score reclassified 26% of patients with a CHADS2 score of 1 to a low annual risk of embolism of 1%. The authors further opined that this risk seems low enough to consider withholding anticoagulant treatment.


The re-analysis of clinical trial data, especially when data from multiple different studies are combined, potentially introduces unaccounted for systemic bias. That being said, this is a conceptually and methodologically excellent study, allowing an estimated quantification of the stroke risk of atrial fibrillation patients with a CHADS2 score of 1, and a demonstration that any such patient with an additional risk factor of age 65-74 or female sex, may be at increased risk for systemic embolization. Put more clinically usefully: these data suggest that any atrial fibrillation patient with a CHADS2 score of 1 who is male and <65 years of age and without history of PAD or CAD, can probably safely be treated without systemic anticoagulation. These data nicely demonstrate the increased discriminatory power of the CHA2DS2-VASc score, and the importance of female sex and age 65-74 as additional embolic risk factors to consider when determining which patients with atrial fibrillation truly benefit from anticoagulant therapy.

Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Stroke, Follow-Up Studies, Pyrazoles, Risk Factors, Peripheral Arterial Disease, Blood Coagulation, Incidence, Cardiology, Embolism, Pyridones

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