OBJECTIVES: Statin dose escalation to reach low-density lipoprotein cholesterol (LDL-C) goals is an established practice. This study analyzes the health economic impact of titrating patients to a target LDL-C of 100mg/dl as recommended by current guidelines. First-line brand rosuvastatin and first-line generic simvastatin protocols are compared. METHODS: A published state-transition model was used, linking age, smoking status, systolic blood pressure, and total cholesterol (TC) to fatal CVD risk using the Belgian SCORE (primary prevention) and Framingham (secondary prevention) equations. Non-fatal risk was based on landmark prevention trials. Patient LDL-C levels (mean/SD, before/after treatment start) were based on the STELLAR trial for simvastatin 20/40/80mg and rosuvastatin 10/20/40mg. Hence, consistent with the STELLAR trial a baseline LDL-C value (mg/dl) of (mean +/- SD) 189 +/- 19 was applied. Other patient data were based on the DISCOVERY-BELUX trial that included Belgian patients. Resource use and unit costs were based on literature and official reimbursement tariffs. Patient groups starting on either rosuvastatin (10mg) or simvastatin (20mg) were compared. Patients not reaching LDL-C target were switched to the next higher dose of the same statin. Simvastatin 80mg patients not reaching target were switched to 20mg and if needed 40mg of rosuvastatin. Cost-effectiveness results were reported as EUR 2009 (direct medical costs from a public payer perspective) per Life Year gained (LYg) for a time horizon of 20 years. RESULTS: EUR/LYg values of 56,481 and 43,884 were found for respectively primary and secondary settings, well below some of the ICER values reported for other health care interventions attracting public reimbursement. Model explorations indicated that cost-effectiveness improved for lower LDL-C targets and higher baseline patient LDL-C levels. CONCLUSIONS: Exclusive titration by rosuvastatin compared to starting patients first on simvastatin, is likely to be cost-effective in patients with elevated LDL-C levels both in primary and secondary prevention.