OBJECTIVES: To compare the efficacy of rosuvastatin 40mg with 20mg for treatment of hypercholesterolaemia and estimate the associated impact on final outcomes based on a meta-analysis of 9 randomised controlled trials (RCTs) from the CRESTOR clinical trial programme. METHODS: A regression analysis of mean LDL-C reduction and difference in event rate between statin and placebo arms in published outcomes studies (4S, CARE, LIPID, HPS), was performed for major clinical endpoints. A model was developed to estimate LDL-C reductions using alternative baseline LDL-C values and the weighted mean difference (WMD) from the meta-analysis. These were combined with results from regression analyses to calculate percentage reduction in cardiovascular events and impact estimated for a population of 100,000. The model was also run using the 95% confidence intervals from the meta-analysis. RESULTS: Meta-analysis demonstrated a significant reduction in LDL-C in favour of rosuvastatin 40mg (WMD –5.26%, 95% CI: –6.08% to –4.43%; p<0.00001). There was no significant heterogeneity identified in the meta-analysis (p=0.42) with low inconsistency in trial results (I2=2.1%). Regression analyses showed good correlation (R2>0.65) between LDL-C reduction and percentage difference in event rates for coronary death, major coronary event, non-fatal myocardial infarction (MI) and revascularisations (CABG and PCTA). Simulations using alternative LDL-C distributions with means varying from 3.40-7.56 mmol/L generated LDL-C reductions of 1.68-3.78 and 1.85-4.18 for rosuvastatin 20mg and 40mg, respectively. These values translated into the following reductions depending on the mean of the distribution: 0.33%-0.74% coronary deaths; 0.72%-1.62% major coronary events; 0.52%-1.17% non-fatal MIs; 0.59%-1.32% revascularisation procedures. Based on a population of 100,000, the incremental benefit of rosuvastatin 40mg over 20mg resulted in the prevention of 329-742 coronary deaths, 721-1,624 major coronary events, 517-1,165 non-fatal MIs and 586-1,321 revascularisation procedures. CONCLUSION: Rosuvastatin 40mg reduces LDL-C significantly more than 20mg. Modelled outcomes suggest this may translate into substantially fewer cardiovascular-related events.