Methodologic Differences Across Studies of Patients With Atrial Fibrillation Lead to Varying Estimates of Stroke Risk

BACKGROUND: Guidelines for anticoagulation in atrial fibrillation (AF) assume that stroke risk scheme point scores correspond to fixed stroke rates. However, reported stroke rates vary widely across AF cohort studies, including studies from the same country. Reasons for this variation are unclear. This study compares methodologies used to assemble and analyze large AF cohorts worldwide and assesses potential bias in estimating stroke rates. METHODS AND RESULTS: From a previous systematic review of AF cohorts, we analyzed studies including at least 5000 patients. We assessed methods used to generate rates of ischemic stroke off anticoagulants, according to a structured inventory of database interrogation methods. Nine studies (497 578 total patients) met our criteria. Overall cohort stroke rates ranged from 0.45% to 7.03% per year. In bivariate study‐level analysis, multiple features were associated with higher stroke rates, including AF identified as inpatients versus outpatients (rate ratio 2.60, 95% confidence interval, 1.19, 5.68), and lack of clinical validation of outcome events (rate ratio 4.09, 95% confidence interval, 1.06, 15.70). European studies reported rates more than 4‐fold higher than North American studies. International Classification of Diseases (ICD) coding schemes for outcomes varied widely. Multiple high rate features coexisted in the same studies. CONCLUSIONS: Among AF cohort studies, differences in the composition, method of assembly, determination of clinical features and outcomes, and analytic approach were strongly associated with reported stroke rates. Our study highlights the need for standardized and validated methodologies for AF cohort assembly and analysis to generate accurate stroke rates to better support anticoagulation guidelines for patients with AF.