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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:39.)
© 2008 American Heart Association, Inc.

Brief Reviews

Is There a Role for Fibrates in the Management of Dyslipidemia in the Metabolic Syndrome?

Philip J. Barter; Kerry-Anne Rye

From The Heart Research Institute, Sydney, and the Faculty of Medicine, University of Sydney, Australia.

Correspondence to Professor Philip Barter, The Heart Research Institute, 114 Pyrmont Bridge Road, Camperdown, NSW, AUSTRALIA 2050. E-mail barterp{at}hri.org.au

Series Editor: Marja-Riitta Taskinen
Metabolic Syndrome and Atherosclerosis
ATVB In Focus

Previous Brief Reviews in this Series:

•Kotrenen A and Yki-Järvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28:27–38.
•Gustafson B, Hammarstedt A, Andersson CX, and Smith U. Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:2276–2283.

The outcomes of fibrate trials have varied: positive with gemfibrozil in the primary prevention Helsinki Heart Study and the secondary prevention VA-HIT trial; positive with reservations in the primary prevention WHO trial (clofibrate); and mixed with bezafibrate in the secondary prevention BIP study and with fenofibrate in the combined primary and secondary prevention FIELD study. Overall, the mixed results, combined with potential for adverse effects when given in combination with statins, have limited the use of these fibrates as cardioprotective agents. However, post hoc analyses of several of the fibrate studies have shown that people with features of the metabolic syndrome, particularly overweight people with high plasma triglyceride levels and low levels of HDL cholesterol, derive a disproportionately large reduction in cardiovascular events when treated with these agents. Thus, there is a strong case for the use of a fibrate to reduce the cardiovascular risk in overweight people with high triglyceride and low HDL-C. However, it should be noted that such people also have their cardiovascular risk reduced by statin therapy. It remains to be determined whether the combination of a fibrate plus statin reduces the risk beyond that achieved with a statin alone.

Features of the metabolic syndrome identify people who have a disproportionately large reduction in cardiovascular events when treated with fibrates. The protection in these people is largely independent of changes in plasma lipids, raising questions about the mechanism of the protection.

Key Words: fibrates • metabolic syndrome • triglyceride • HDL • cardiovascular events

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