Fibrates The Other Life-saving Lipid Drugs

Fibrates The Other Life-saving Lipid Drugs

Fazio Sergio
US Endocrine Review 2005 - September 2005
Published: October 2008
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The main controversy in the area of lipid management today is related to the usefulness of ‘non-statin’ agents to maximize cardiovascular risk reduction in particular patient types, such as those with diabetes and metabolic syndrome. Fibrate drugs, such as gemfibrozil (Lopid) and fenofibrate (TriCor), are undoubtedly the best tools to address the condition characterized by high triglycerides, low high-density lipoprotein (HDL), and small dense low-density lipoprotein (LDL) (atherogenic dyslipidemia), but the most recent guidelines from both the American Diabetes Association (ADA) and the National Cholesterol Education Panel continue to focus on LDL control as the target of therapy.

However, statin-based interventions are unlikely to correct problems of triglycerides and HDL, whereas the use of fibrates has a stronger effect on the atherogenic dyslipidemia and might even produce significant LDL reduction in some patients. Thus, physicians dealing with the common phenotype of insulin resistance are presented with a practical problem – the use of statins primarily to control LDL, or the use of fibrates primarily to control triglycerides and HDL.Well-designed outcome studies published in the last few years have shown the value of fibrate therapy in patients with obesity, the metabolic syndrome, and diabetes, particularly when LDL levels are below 130mg/dl and when triglycerides and HDL levels are only modestly abnormal.

Mechanism of Action of Fibrates
Gemfibrozil and fenofibrate are the fibrates currently approved for use in the US and, in addition to these, bezafibrate and ciprofibrate are also available in Europe. The fibrates have been in use since the late 1960s, and for about 25 years their mode of action was not known. The relatively recent understanding of the molecular mechanisms of fibrate action1 represents one of the biggest breakthroughs in cardiovascular pharmacology. Fibrates are now known to alter the transcription of several genes involved in lipoprotein metabolism and other pathways.2 Fibrates are able to activate gene transcription because they are synthetic ligands for peroxisome proliferator-activated receptor (PPAR)−α, a ligand-activated transcription factor and member of the nuclear hormone receptor superfamily. PPARα transmits signals from lipid-soluble factors, such as fatty acids, eicosanoids, hormones and vitamins, to genes in the nucleus by binding to DNA within specific response elements (PPREs).1

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