This randomised, double-blind study evaluated the efficacy and safety of ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg tablet compared to doubling the atorvastatin (ATV) dose in hypercholesterolaemic patients with atherosclerotic or coronary heart disease (CHD). The study group included 435 male and female CHD patients (aged >or=18 years) who had not achieved their low-density lipoprotein cholesterol (LDL-C) goal of <2.50 mmol/l while on a stable dose of ATV 10 mg for >or=6 weeks. After a 1-week diet/stabilisation period, patients with LDL-C >or=2.50 mmol/l and <or=4.20 mmol/l were randomised (1:1) to EZE/SIMVA 10/20 mg/day (n = 221) or ATV 20 mg/day (n = 214) for 6 weeks. The primary efficacy objective was to determine the per cent reduction from baseline in LDL-C at week 6. EZE/SIMVA 10/20 mg produced significantly greater mean per cent changes from baseline in LDL-C compared with ATV 20 mg (-32.8 vs. -20.3%; p </= 0.001). A significantly greater proportion of patients achieved an LDL-C goal <2.50 mmol/l with EZE/SIMVA than ATV (77.9 vs. 51.9%; p <or= 0.001). Significant improvements in total cholesterol (-20.3 vs. -13.0%), non-high-density lipoprotein cholesterol (non-HDL-C) (-27.9 vs. -17.0%), apolipoprotein B (-23.4 vs. -14.7%) and HDL-C (1.8 vs. -0.4%) were observed after switching to EZE/SIMVA 10/20 mg for 6 weeks (p < 0.05 for all parameters). EZE/SIMVA 10/20 mg was generally well tolerated, with an overall safety profile similar to that of ATV 20 mg. EZE/SIMVA 10/20 mg produced superior lipid-altering efficacy by dual inhibition of cholesterol synthesis and intestinal absorption compared with doubling the dose of ATV from 10 to 20 mg.