The role of fibrates in managing hyperlipidemia: mechanisms of action and clinical efficacy.

At a time when the lipid management guidelines give more and more emphasis to the identification and treatment of high-risk patients with the metabolic syndrome and diabetes, there is an obvious need to balance the known effects of low-density lipoprotein (LDL) lowering with the new evidence of clinical efficacy derived from the adjustment of high-density lipoprotein (HDL) and triglyceride levels. Whereas the statins remain the drug of choice for patients who need to reach the LDL goal, fibrate therapy may represent the best intervention for subjects with atherogenic dyslipidemia and an LDL already close to goal. In addition, the concomitant use of fibrates may significantly reduce cardiovascular risk in patients whose LDL is controlled by statin therapy. In this review, we evaluate the pharmacologic properties of the fibrate drugs, with particular attention to the effects of peroxisome proliferator activated receptor a activation in the control of dyslipidemia as well as in the attenuation of arterial inflammation. Clinical trials of fibrates, such as the Helsinki Heart Study, Veterans Affairs High-density lipoprotein Intervention Trial, Diabetes Atherosclerosis Intervention Study, and Bezafibrate Infarction Prevention trial, have conjured up a scenario for the clinical utility of fibrates and their possible superiority to statins in the management of obese, insulin-resistant, and diabetic patients presenting with near-goal LDL and inappropriate HDL and triglyceride levels.