Multiple statin formulations are available that effectively lower cholesterol levels. Determining which statin preparation to prescribe depends on several factors, including cost, adverse effects, and efficacy. Karalis and associates compared the efficacy and safety of starting and maximal dosages of atorvastatin and simvastatin using two end points: (1) the percent change in low-density lipoprotein (LDL) cholesterol level from baseline to six weeks of treatment, and (2) the percent change in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and very-low-density lipoprotein (VLDL) cholesterol levels from baseline to six weeks.
The study was a multicenter, prospective, randomized, open-label, blinded end-point study, comparing once-daily doses of 10 mg of atorvastatin with 20 mg of simvastatin, and comparing 80 mg of atorvastatin (40 mg, twice daily) with 80 mg of simvastatin. Men and women aged 18 to 80 years, with dyslipidemia and with or without coronary heart disease, were included in the study. The subjects received appropriate diet instruction and were randomized into one of the four treatment groups. Exclusion criteria included marked obesity, renal or hepatic disease, uncontrolled diabetes, elevated creatine phosphokinase level, recent myocardial infarction, revascularization, unstable angina, or use of medications that affect lipid levels or contraindicate the concomitant use of statins. Patients who had been taking a lipid-lowering medication were included after discontinuing that drug for at least four weeks. Laboratory parameters and potential adverse effects were monitored.
Among the 1,694 patients included in the study, compliance with the medication regimen was greater than 90 percent in all four study groups. Although there were differences in sex and blood pressure among the groups, these factors were not believed to have affected the outcome conclusions.
All four treatment groups had significant reductions in LDL cholesterol from baseline. The decrease was significantly greater with 10 mg of atorvastatin than with 20 mg of simvastatin at both the starting dosages and the maximal dosages, and more patients taking atorvastatin achieved the LDL cholesterol goals established by the National Cholesterol Education Program (NCEP) at six weeks (see accompanying table).
All treatment groups also showed significant decreases at week 6 in total cholesterol, triglycerides, apolipoprotein B, and VLDL cholesterol levels, as well as increases in HDL cholesterol. Adverse effects were uncommon and generally mild to moderate, with some patients demonstrating increases in creatine phosphokinase, alanine aminotransferase, or aspartate aminotransferase levels. No cases of myositis occurred in any participant.
|CHD risk factors||LDL cholesterol goal|
|Fewer than two||< 160 mg per dL (4.15 mmol per L)|
|Two or more||< 130 mg per dL (3.35 mmol per L)|
|Established CHD||100 mg per dL (2.60 mmol per L)|
The authors conclude that although all treatments improved dyslipidemia, treatment reductions of LDL cholesterol within six weeks of treatment initiation were greater with atorvastatin than with simvastatin among this population of patients. Atorvastatin, therefore, provided greater efficacy in achieving NCEP goals for LDL cholesterol levels. Atorvastatin also provided a greater reduction of total cholesterol, triglycerides, apolipoprotein B, and VLDL cholesterol levels. HDL cholesterol levels increased with all treatments, but high-dose simvastatin demonstrated a significantly greater HDL effect.