Objectives: This single-blind, multicentre study in a large cohort of hypercholesterolaemic patients with or without coronary heart disease (CHD) was designed to evaluate the additional low density lipoprotein cholesterol (LDL-C)— lowering effect of atorvastatin over milligram-equivalent doses of simvastatin.
Methods: 378 patients treated with either simvastatin 20 or 40mg, with baseline LDL-C values >2.6 mmol/L, were randomised to four groups: patients on 20mg simvastatin were randomised to either simvastatin 20mg (n = 129) or atorvastatin 20mg (n = 124), and patients on 40mg simvastatin were randomised to simvastatin 40mg (n = 64) or atorvastatin 40mg (n = 61). The investigator was blinded for study medication during the 8-week treatment phase, the patient was not. Lipid profiles were measured at screening, randomisation and at study completion. The primary efficacy parameter was the relative change in LDL-C level within and between groups. Statistical significance was assessed with analysis of variance.
Results: No major differences in baseline patient characteristics were found with regard to demographic variables, vital signs, cardiovascular risk factors, concomitant medication or lipid profiles. The mean (±SD) relative decreases of LDL-C from baseline were: 14.0 ± 14.1% for atorvastatin 20mg (n = 107) versus 3.3 ± 14.1% for simvastatin 20mg (n = 108) [p = 0.0001], and 14.7 ± 15.2% for atorvastatin 40mg (n = 55) versus 2.9 ± 12.7% for simvastatin 40mg (n = 54) [p = 0.0001]. The relative change of LDL-C from baseline in the overall atorvastatin group (n = 162) versus the overall simvastatin group (n = 162) was 14.2 ± 14.4% versus 3.2 ± 13.6% (p = 0.0001). This involved an additional decrease of 11% in the atorvastatin versus the simvastatin group. The percentage of high risk patients according to the European Atherosclerosis Society/National Cholesterol Education Program (EAS/NCEP) who initially did not meet these goals but reached them at week 8, was 48/34% (for atorvastatin 20mg) versus 20/14% (for simvastatin 20mg) [p = 0.005 and p = 0.007, respectively], and 58/18% (for atorvastatin 40mg) versus 24/10% (for simvastatin 40mg) [p = 0.005 and not significant, respectively].
Conclusion: Our results indicated that patients with hypercholesterolaemia on simvastatin 20 or 40mg who are switched to a milligram-equivalent dose of atorvastatin, will reach significantly lower LDL-C values within 8 weeks of treatment, with a greater percentage of high risk patients reaching their EAS or NCEP targets.