OBJECTIVES: Non-achievement of combined optimal lipid values (OLVs) (LDL-C, HDL-C, and TG) is associated with an increased risk of cardiovascular events (CVE). Data comparing combination lipid therapy effects on multiple lipid abnormalities and CVE reduction are limited. We modeled CVE risk reduction with extended release niacin/simvastatin (ERN/S) , simvastatin/ezetimibe (S/E), extended release niacin (ERN), simvastation (S), and ezetimibe (E), in a large managed care (MCO) population. METHODS: Patients were selected from a 2.1 million record database if they had a lipid panel between January 1, 2000 and December 31, 2001, no concomitant lipid therapy, and continuous eligibility for 24 months. Cardiovascular risk and CVEs (determined by ICD-9/CPT codes, prescription records, and ER visits/hospitalizations) for each patient were identified, and OLV achievement was modeled using product labeling at maximum doses (assuming additive effects for ERN/S). Population CVE rate during 30±12 months of follow-up was 15.16% with an odds ratio 0.69 (CI: 0.61 to 0.81). Achievement (18%) vs non-achievement (82%) of OLVs was utilized to estimate CVE rates associated with modeled OLV achievement rates. RESULTS: We analyzed 44,351 patients; 50% male, age 65±13 years. Modeled lipid therapy resulted in combined OLV achievement of: ERN/S 66.2%, S/E 48.4%, ERN 36.4%, S 46.3%, and E 18.4% (×2 p<0.05 all vs baseline; ERN/S vs S/E, ERN, and S; S/E vs S and E). Based upon achievement of OLV, the predicted population CVE rates were reduced from baseline (15.16%) to: ERN/S 9.4 % (RRR: 38%), S/E 11.5% (RRR: 24%), ERN 13.0% (RRR: 14%), S 11.8% (RRR: 22%), and E 15.1% (RRR: 0.4%)(p<0.05 for all except E vs baseline; ERN/S vs S/E, ERN, and S; S/E vs E). CONCLUSION: In this MCO population, OLVs were more frequently achieved with ERN/S versus S/E, ERN, and S. Attaining combined OLVs with combination ERN/S resulted in significant reductions in projected CVE rates.