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To compare cardiovascular (CV) event rates and risk in patients without previous CV disease in whom atorvastatin or simvastatin was newly initiated in a managed care setting.Patients aged 18 to 64 years in whom atorvastatin or simvastatin was newly initiated between January 1, 2003, and December 31, 2006, and who had no history of CV disease and at least 12 months of preindex and 3 months of postindex continuous eligibility in a managed care health plan, were identified using administrative claims from the HealthCore Integrated Research Database. Descriptive statistics were reported for sample characteristics. Unadjusted CV event rates were compared between treatment groups. A multivariate Cox proportional hazards model was developed to evaluate adjusted CV risk in all patients, as well as in a subset of patients with diabetes mellitus.A total of 168,096 patients in the atorvastatin group and 51,333 patients in the simvastatin group were analyzed. Mean ± SD age was 50.2 ± 9.0 years for patients using atorvastatin and 50.6 ± 9.0 years for patients using simvastatin. Mean ± SD follow-up time was 664.2 ± 386.2 days for the atorvastatin group and 511.4 ± 359.8 days for the simvastatin group. Mean ± SD dose and mean ± SD therapy duration for patients taking simvastatin were 29.1 ± 15.1 mg and 188.6 ± 236.3 days, respectively, compared with 16.8 ± 11.1 mg and 241.8 ± 292.0 days, respectively, for patients taking atorvastatin. Unadjusted CV event rates were lower with use of atorvastatin than with simvastatin (hazard ratio, 0.80; 95% confidence interval, 0.75-0.84; P < .001). Adjusting for demographic/clinical characteristics, patients taking atorvastatin experienced a 13% risk reduction in total CV events during the entire follow-up period compared with those who were taking simvastatin (hazard ratio, 0.87; 95% confidence interval, 0.82-0.92; P < .001). No significant differences in CV events were found between patients taking atorvastatin or simvastatin in the diabetes mellitus subset (n = 36,969).In a managed care population with no history of CV disease, risk of CV events was lower among patients taking atorvastatin compared with patients taking simvastatin, after adjusting for known baseline differences.