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The British Journal of Diabetes & Vascular Disease
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Review: Fibrates: therapeutic review

M John Chapman

Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 551, Dyslipoprotéinemies et Athérosclérose: Génétique, Métabolisme et Thérapeutique, Hôpital de la Pitié, 83, Bd de l'Hôpital — Pavilion B. Delessert, 75651 Paris, Cedex 13, France, chapman{at}chups.jussieu.fr

As agonists of the peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), fibrates are established, effective and well-tolerated agents in the management of atherogenic dyslipidaemia. Key actions of fibrates include a reduction in elevated triglyceride levels (by up to 50%) and a rise in high-density lipoprotein cholesterol (HDL-C) concentrations (typically by 5—15%). Fibrates promote a shift from small, dense low-density lipoprotein (LDL) to larger more buoyant particles, which are less susceptible to oxidation and possess higher binding affinity for removal by the non-atherogenic LDL receptor pathway. Thus, fibrates can correct lipid abnormalities commonly observed in patients with type 2 diabetes and metabolic syndrome. Clinical evidence has demonstrated the value of fibrate therapy in secondary and primary prevention settings, as well as in patients with type 2 diabetes. However, FIELD, the largest fibrate study to date in diabetic patients, predominantly in a primary prevention setting, showed a non-significant 11% reduction in the primary end point of coronary heart disease death and non-fatal myocardial infarction with fenofibrate, although total cardiovascular events, corresponding to the secondary end point, were significantly reduced by 11% (p=0.035). It is possible that risk reduction with fenofibrate may have been attenuated by the two-fold greater drop-in use of statin therapy in the placebo group. However, the interesting results of fenofibrate on attenuation of microangiographic symptomatology potentially suggest a new recommendation for fibrate therapy, although further studies are required to validate these findings.

Key Words: fibrate • dyslipidaemia • type 2 diabetes • cardiovascular risk • microangiography.

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The British Journal of Diabetes & Vascular Disease, Vol. 6, No. 1, 11-19 (2006)
DOI: 10.1177/14746514060060010201
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