Dose-response of simvastatin in primary hypercholesterolemia

In an 8-week, placebo-controlled multicenter study, the efficacy of dose levels of simvastatin 2.5, 5, 10, 20, and 40 mg was evaluated in 166 patients with hypercholesterolemia, of whom 163 completed the trial. The entry criteria were serum total cholesterol (TCHOL) between 6.2 and 7.8 mM and low-density lipoprotein (LDL) cholesterol between 4.3 and 50 mM on a standard diet and after the 2-week run-in period of placebo treatment. Mean percentage changes in serum lipids in each simvastatin-treated group from baseline were statistically significant. Of treated patients, 0% (placebo), 11% (2.5 mg), 7% (5 mg), 33% (10 mg), 42% (20 mg) and 55% (40 mg) had at least 40% reduction from baseline LDL cholesterol value. After 8 weeks of treatment, 0% (placebo), 11% (2.5 mg), 25% (5 mg), 26% (10 mg), 31% (20 mg), and 55% (40 mg) of patients treated reached a TCHOL level of < or = 5.2 mM. There was a significant linear dose response with regard to the decrease in LDL cholesterol, TCHOL, and triglycerides (TG) and the increase in high-density lipoprotein (HDL) cholesterol after 8 weeks of therapy. No serious clinical or laboratory adverse events related to simvastatin were observed even at higher doses. At each dose level, simvastatin reduced TCHOL and LDL cholesterol. Doses of simvastatin > or = 5 mg moderately increased HDL cholesterol and reduced serum TG. Simvastatin therapy resulted in major improvement in serum lipoprotein profile, particularly at higher doses.