Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia

J Am Coll Cardiol. 2005 May 17;45(10):1649-53. doi: 10.1016/j.jacc.2005.02.052.


Objectives: 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 No patients were withdrawn from the study as the result of serious adverse effects.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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Arteriosclerosis / blood
  • Arteriosclerosis / diagnostic imaging
  • Arteriosclerosis / drug therapy
  • Atorvastatin
  • Brachial Artery / diagnostic imaging
  • Brachial Artery / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fenofibrate / administration & dosage*
  • Fenofibrate / adverse effects
  • Follow-Up Studies
  • Heptanoic Acids / administration & dosage*
  • Heptanoic Acids / adverse effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hyperlipidemia, Familial Combined / blood
  • Hyperlipidemia, Familial Combined / diagnostic imaging
  • Hyperlipidemia, Familial Combined / drug therapy*
  • Hypolipidemic Agents / administration & dosage*
  • Hypolipidemic Agents / adverse effects
  • Lipids / blood*
  • Male
  • Middle Aged
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / drug therapy
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Treatment Outcome
  • Ultrasonography


  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Lipids
  • Pyrroles
  • Atorvastatin
  • Fenofibrate