Five multicenter, randomized, double-blind, placebo-controlled studies were conducted in France to compare the efficacy and safety of once-daily
simvastatin treatment (10-40 mg/day) with conventional
therapy with
gemfibrozil 900 mg/day,
ciprofibrate 100 mg/day,
bezafibrate 400 mg/day, and
fenofibrate 300 or 400 mg/day in a total of 800 patients with
hypercholesterolemia.
Simvastatin was associated with statistically significantly greater (p < or = 0.01) mean percent reductions in plasma
low-density lipoprotein (
LDL) cholesterol compared with each of the five
fibrate regimens, even when administered at its recommended starting dose of 10 mg/day. Furthermore, approximately 90% of patients treated once daily with
simvastatin experienced an at least 20% decrease in plasma
LDL cholesterol compared with only 36 to 68% of patients treated with the individual
fibrate agents (p < or = 0.05). The effectiveness of
simvastatin in reducing
LDL cholesterol did not differ as a function of the baseline plasma concentrations of total
cholesterol or
triglycerides. In contrast, the effectiveness of
fibrate therapy in lowering plasma
LDL cholesterol levels was significantly diminished (p < or = 0.05) among patients with
triglyceride concentrations > 1.7 mmol/l. Plasma
high-density lipoprotein (
HDL) cholesterol levels were increased by approximately 10%
after treatment with
simvastatin or the
fibrates. Although
fibrate therapy was more effective overall in lowering plasma
triglyceride levels, the effectiveness of
simvastatin in reducing plasma
triglyceride levels was generally 2- to 4-fold greater in patients with
hypercholesterolemia associated with
triglyceride levels > or = 2.3 mmol/l than in those with
hypercholesterolemia associated with
triglyceride levels < 2.3 mmol/l. The results of these studies confirm the superiority of
simvastatin to standard
fibrate therapy in reducing plasma levels of total and
LDL cholesterol. They further indicate that once-daily treatment with
simvastatin is effective in patients with isolated
hypercholesterolemia or
hypercholesterolemia associated with elevated
triglyceride levels.