BACKGROUND: The CHA2DS2-VASc decision rule is widely recommended for estimating stroke risk in patients with atrial fibrillation (AF) though validation studies show ambiguous and conflicting results.

OBJECTIVES: We aimed to (1) review existing studies validating CHA2DS2-VASc in AF patients not (yet) anticoagulated, (2) meta-analyze estimates of stroke risk per score, and (3) explore sources of heterogeneity across the validation studies.

METHODS: We performed a systematic literature review and random effects meta-analysis of studies externally validating CHA2DS2-VASc in AF patients not on anticoagulants. To explore between-study heterogeneity in stroke risk, we stratified studies to the clinical setting in which patient enrollment started, and performed meta-regression.

RESULTS: In total 19 studies were evaluated with over two million person-years of follow-up. In studies recruiting AF patients in hospitals, stroke risk for a score of zero, one and two were 0.4% (approximate 95% prediction interval (PI) 0.2 to 3.2%), 1.2% (95% PI 0.1 - 3.8%) and 2.2% (95% PI 0.03 - 7.8%), respectively. This was consistently higher than studies recruiting patients from the open general population, with risks of 0.2% (95% PI 0.0 - 0.9%), 0.7% (0.3 - 1.2%) and 1.5% (95% PI 0.4 - 3.3%) for score zero to two respectively. Heterogeneity as reflected by the wide prediction intervals could not be fully explained by meta-regression.

CONCLUSIONS: Studies validating CHA2DS2-VASc demonstrate high heterogeneity in predicted stroke risks for different scores.