Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia.
To investigate the lipoprotein effect of fenofibrate in hypercholesterolemia or combined hyperlipidemia (types II A and II B hyperlipidemias, respectively), 240 patients were recruited and 227 randomized to a double-blind randomized trial lasting 24 weeks and 192 patients continued to participate in an open-label phase for another 24 weeks. A 100-mg dose of fenofibrate or a matching placebo was given three times daily. Fenofibrate side effects in excess of placebo affected 6 percent of fenofibrate users and were confined almost entirely to skin rashes. In 180 hypercholesterolemic patients randomly assigned to receive fenofibrate versus placebo, triglyceride and very low-density lipoprotein cholesterol levels decreased 38 percent, total cholesterol levels decreased 17.5 percent, and low-density lipoprotein cholesterol levels decreased 20.3 percent with fenofibrate treatment. High-density lipoprotein cholesterol levels increased 11.1 percent with a decrease in the low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio of 27 percent. All differences were statistically significant (p less than 0.01). In combined hyperlipidemic (type II B) patients, triglyceride levels decreased by 45 percent, very low-density lipoprotein cholesterol levels decreased 52.7 percent, total cholesterol levels decreased 16 percent, low-density lipoprotein cholesterol levels decreased 6 percent, and high-density lipoprotein levels increased 15.3 percent for a low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio decrease of 13 percent. All differences were again statistically significant (p less than 0.01). In both groups of patients, the onset of the drug effect was generally rapid, with maximal total and low-density lipoprotein cholesterol level lowering achieved within four weeks in hypercholesterolemic patients and maximal triglyceride and cholesterol level lowering in hypertriglyceridemic patients achieved in two weeks. Maximum high-density lipoprotein increases occurred after four weeks in type II A patients and 12 to 16 weeks in type II B patients. Fenofibrate is a well-tolerated drug in the fibric acid series and has putatively beneficial effects on triglyceride, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein cholesterol concentrations in both type II A and type II B hyperlipidemic patients. If the lipid hypothesis of atherosclerosis applies to the lipoprotein changes induced by fenofibrate, reductions in cardiovascular disease risk in both type II A and II B hyperlipidemic patients should result from fenofibrate treatment.
Knopp
R H
RH
Department of Medicine, University of Washington, Seattle 98104.
Brown
W V
WV
Dujovne
C A
CA
Farquhar
J W
JW
Feldman
E B
EB
Goldberg
A C
AC
Grundy
S M
SM
Lasser
N L
NL
Mellies
M J
MJ
Palmer
R H
RH
D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000627:therapeutic use*; D011897:Random Allocation
D008074:Lipoproteins; D011422:Propionates; D011345:Fenofibrate