Comparison of the efficacy of simvastatin and standard fibrate therapy in the treatment of primary hypercholesterolemia and combined hyperlipidemia.
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.
Bruckert
E
E
Service d'Endocrinologie-Métabolisme, Groupe hospitalier Pitié-Salpétrière, Paris, France.
De Gennes
J L
JL
Malbecq
W
W
Baigts
F
F
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001629:Bezafibrate / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D005232:Fatty Acids, Volatile / Q000627:therapeutic use*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D058607:Fibric Acids; D015248:Gemfibrozil / Q000627:therapeutic use; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019821:Simvastatin; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005232:Fatty Acids, Volatile; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; D002995:Clofibric Acid; D008148:Lovastatin; D019821:Simvastatin; C019304:ciprofibrate; D015248:Gemfibrozil; D011345:Fenofibrate; D001629:Bezafibrate