Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome.
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.
Vega
Gloria Lena
GL
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
Ma
Patrick T S
PT
Cater
Nilo B
NB
Filipchuk
Neil
N
Meguro
Shinichi
S
Garcia-Garcia
Ana Barbara
AB
Grundy
Scott M
SM
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*
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D000960:Hypolipidemic Agents; D008074:Lipoproteins; C030104:lipoprotein cholesterol; D002784:Cholesterol; D019821:Simvastatin; D011345:Fenofibrate