Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia

AbstractFive 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 ≪ 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 ≪ 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 ≪ 0.05) among patients with triglyceride concentrations > 1.7 mmol/1. Plasma highdensity 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 ≫ 2.3 mmol/1 than in those with hypercholesterolemia associated with triglyceride levels < 2.3 mmol/1. 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.