title: Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome.
abstract: Combined hyperlipidemia predisposes subjects to coronary heart disease. Two lipid abnormalities--increased cholesterol and atherogenic dyslipidemia--are potential targets of lipid-lowering therapy. Successful management of both may require combined drug therapy. Statins are effective low-density lipoprotein (LDL) cholesterol-lowering drugs. For atherogenic dyslipidemia (high triglycerides, small LDL, and low high-density lipoprotein [HDL]), fibrates are potentially beneficial. The present study was designed to examine the safety and efficacy of a combination of low-dose simvastatin and fenofibrate in the treatment of combined hyperlipidemia. It was a randomized, placebo-controlled trial with a crossover design. Three randomized phases were employed (double placebo, simvastatin 10 mg/day and placebo, and simvastatin 10 mg/day plus fenofibrate 200 mg/day). Each phase lasted 3 months, and in the last week of each phase, measurements were made of plasma lipids, lipoprotein cholesterol, plasma apolipoproteins B, C-II, and C-III and LDL speciation on 3 consecutive days. Simvastatin therapy decreased total cholesterol by 27%, non-HDL cholesterol by 30%, total apolipoprotein B by 31%, very low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL) cholesterol by 37%, VLDL + IDL apolipoprotein B by 14%, LDL cholesterol by 28%, and LDL apolipoprotein B by 21%. The addition of fenofibrate caused an additional decrease in VLDL + IDL cholesterol and VLDL + IDL apolipoprotein B by 36% and 32%, respectively. Simvastatin alone caused a small increase in the ratio of large-to-small LDL, whereas the addition of fenofibrate to simvastatin therapy caused a marked increase in the ratio of large-to-small LDL species. Simvastatin alone produced a small (6%) and insignificant increase in HDL cholesterol concentrations. When fenofibrate was added to simvastatin therapy, HDL cholesterol increased significantly by 23%. No significant side effects were observed with either simvastatin alone or with combined drug therapy. Therefore, a combination of simvastatin 10 mg/day and fenofibrate 200 mg/day appears to be effective and safe for the treatment of atherogenic dyslipidemia in combined hyperlipidemia.
authors.affiliation: The Center for Human Nutrition, Department of Clinical Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9052, USA. Gloria.vega@utsouthwestern.edu
authors.forename: Gloria Lena
authors.initials: GL
authors.lastname: Vega
authors.forename: Patrick T S
authors.initials: PT
authors.lastname: Ma
authors.forename: Nilo B
authors.initials: NB
authors.lastname: Cater
authors.forename: Neil
authors.initials: N
authors.lastname: Filipchuk
authors.forename: Shinichi
authors.initials: S
authors.lastname: Meguro
authors.forename: Ana Barbara
authors.initials: AB
authors.lastname: Garcia-Garcia
authors.forename: Scott M
authors.initials: SM
authors.lastname: Grundy
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage*; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D000960:Hypolipidemic Agents; D008074:Lipoproteins; C030104:lipoprotein cholesterol; D002784:Cholesterol; D019821:Simvastatin; D011345:Fenofibrate