, Volume 71, Issue 14, pp 1917-1946
Date: 24 Sep 2012


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Fenofibrate is a fibric acid derivative indicated for the treatment of severe hypertriglyceridaemia and mixed dyslipidaemia in patients who have not responded to nonpharmacological therapies. The lipid-modifying effects of fenofibrate are mediated by the activation of peroxisome proliferator-activated receptor-α. Fenofibrate also has nonlipid, pleiotropic effects (e.g. reducing levels of fibrinogen, C-reactive protein and various pro-inflammatory markers, and improving flow-mediated dilatation) that may contribute to its clinical efficacy, particularly in terms of improving microvascular outcomes.

Fenofibrate improves the lipid profile (particularly triglyceride [TG] and high-density lipoprotein-cholesterol [HDL-C] levels) in patients with dyslipidaemia. Compared with statin monotherapy, fenofibrate monotherapy tends to improve TG and HDL-C levels to a significantly greater extent, whereas statins improve low-density lipoprotein-cholesterol (LDL-C) and total cholesterol levels to a significantly greater extent. Fenofibrate is also associated with promoting a shift from small, dense, atherogenic LDL particles to larger, less dense LDL particles. Combination therapy with a statin plus fenofibrate generally improves the lipid profile to a greater extent than monotherapy with either agent in patients with dyslipidaemia and/or type 2 diabetes mellitus or the metabolic syndrome.

In the pivotal FIELD and ACCORD trials in patients with type 2 diabetes,fenofibrate did not significantly reduce the risk of coronary heart disease events to a greater extent than placebo, and simvastatin plus fenofibrate did not significantly reduce the risk of major cardiovascular (CV) events to a greater extent than simvastatin plus placebo. However, the risk of some nonfatal macrovascular events and the incidence of certain microvascular outcomes were reduced significantly more with fenofibrate than with placebo in the FIELD trial, and in the ACCORD trial, patients receiving simvastatin plus fenofibrate were less likely to experience progression of diabetic retinopathy than those receiving simvastatin plus placebo. Subgroup analyses in the FIELD and ACCORD Lipid trials indicate that fenofibrate is of the greatest benefit in decreasing CV events in patients with atherogenic dyslipidaemia.

Fenofibrate is generally well tolerated when administered alone or in combination with a statin.

Thus, in patients with dyslipidaemia, particularly atherogenic dyslipidaemia, fenofibrate is a useful treatment option either alone or in combination with a statin.

Various sections of the manuscript reviewed by: D. Bhatnagar, Diabetes Centre, The Royal Oldham Hospital, Oldham, UK; M.B. Elam, Department of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, TN, USA; M. Farnier, Rond Point de la Nation, Point Médical, Dijon, France; S.M. Mohiuddin, The Creighton Cardiac Center, Omaha, NB, USA.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘fenofibrate’ was identified by searching databases since 1996 (including MEDLINE and EMBASE and in-house AdisBase), bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘fenofibrate’ and (‘hyperlipidaemia’ or ‘hyperlipidemia’ or ‘dyslipidaemia’ or ‘dyslipidemia’). Searches were last updated 17 August 2011.
Selection: Studies in patients with dyslipidaemia who received fenofibrate. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Fenofibrate, dyslipidaemia, metabolic syndrome, pharmacodynamics, pharmacokinetics, therapeutic use, type 2 diabetes mellitus.