OBJECTIVES: Compare combined optimal lipid value (OLV) goal attainment [low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)] between patients initiating niacin extended-release [NER] + simvastatin (NER/S) and ezetimibe + simvastatin (E/S) combination therapies among patients in a managed care setting. METHODS: An observational cohort study of patients aged = 18 initiating NER/S (addition of NER to existing simvastatin therapy) or E/S therapy between January 1, 2001 and June 30, 2006 (index date) was performed using the HealthCore Integrated Research Database. Patients with a minimum 24 months of follow-up and diagnosis of cardiovascular disease during the 12 months prior to index date were included. A propensity score regression model for treatment selection was created after adjusting for age, gender, baseline LDL-C, HDL-C, and TG, and Deyo-Charlson comorbidity index (DCI) score. The propensity score was included in a multivariate logistic regression model to estimate combined OLV goal attainment (per treatment guidelines) between the groups. RESULTS: A total of 883 patients were identified initiating NER/S (n=445) or E/S (n=438). E/S patients were younger (51.4±8.4 years vs. 54.0±8.5 years; p<0.001) and less likely to be male (55.3% vs. 81.1%; p<0.001). Fewer E/S patients were likely to have prior hypertension (67.1% vs. 80.2%; p<0.001) and congestive heart disease (17.1% vs. 45.6%; p<0.001) versus NER/S patients, though the pre-index DCI score was statistically non-significant between the groups (0.7 ± 1.1: E/S vs. 0.8 ± 1.1: NER/S; p=0.097). Logistic regression showed that NER/S patients were 64% more likely to achieve combined OLV goal attainment as compared to E/S treated patients [Odds Ratio: 1.64 (95% CI: 1.02 – 2.62); p=0.04]. CONCLUSIONS: NER/S treatment was associated with a likelihood of combined OLV goal attainment versus E/S patients. Further research on impact of early initiation of NER/S therapy emphasizing multiple lipid parameter management versus LDL-C-only focused treatment strategies comes is warranted.