Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia.
OBJECTIVE
We compared vascular and metabolic responses (and adverse responses) to statin and fibrate therapies alone or in combination in patients with combined hyperlipidemia.


BACKGROUND
The mechanisms of action for statins and fibrates are distinct.


METHODS
Fifty-six patients were given atorvastatin 10 mg and placebo, atorvastatin 10 mg and fenofibrate 200 mg, or fenofibrate 200 mg and placebo daily during each two-month treatment period of a randomized, double-blind, placebo-controlled crossover trial with two washout periods of two months' each.


RESULTS
Lipoproteins were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone. Flow-mediated dilator response to hyperemia and plasma high-sensitivity C-reactive protein and fibrinogen levels were changed to a greater extent with combined therapy when compared with atorvastatin or fenofibrate alone (p < 0.001, p = 0.182, and p = 0.015 by analysis of variance [ANOVA], respectively). The effects of combined therapy or fenofibrate alone on plasma adiponectin levels and insulin sensitivity (determined by the Quantitative Insulin-Sensitivity Check Index [QUICKI]) were significantly greater than those of atorvastatin alone (p = 0.022 for adiponectin and p = 0.049 for QUICKI by ANOVA). No patients were withdrawn from the study as the result of serious adverse effects.


CONCLUSIONS
Combination therapy is safe and has beneficial additive effects on endothelial function in patients with combined hyperlipidemia.
Koh
Kwang Kon
KK
Department of Cardiology, Gachon Medical School, Incheon, Korea. kwangk@ghil.com
Quon
Michael J
MJ
Han
Seung Hwan
SH
Chung
Wook-Jin
WJ
Ahn
Jeong Yeal
JY
Seo
Yiel-Hea
YH
Choi
In Suck
IS
Shin
Eak Kyun
EK
D001161:Arteriosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D000069059:Atorvastatin; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014463:Ultrasonography
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin; D011345:Fenofibrate