Use of fibrates in the metabolic syndrome: A review

Abstract

The use of fibrates in the treatment of dyslipidaemia has changed significantly over recent years. Their role appeared clear at the start of this century. The Helsinki Heart Study and Veterans Affairs High-Density Cholesterol Intervention Trial suggested significant benefit, especially in patients with atherogenic dyslipidaemia. However, this clarity disintegrated following the negative outcomes reported by the Bezafibrate Infarction Prevention, Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes randomised controlled trials. In this review we discuss these and other relevant trials and consider patient subgroups such as those with the metabolic syndrome and those needing treatment to prevent the microvascular complications associated with diabetes in whom fibrates may be useful. We also discuss observations from our group that may provide some explanation for the varying outcomes reported in large trials. The actions of fibrates in patients who are also on statins are interesting and appear to differ from those in patients not on statins. Understanding this is key as statins are the primary lipid lowering agents and likely to occupy that position for the foreseeable future. We also present other features of fibrate treatment we have observed in our clinical practice; changes in creatinine, liver function tests and the paradoxical high density lipoprotein reduction. Our purpose is to provide enough data for the reader to make objective decisions in their own clinical practice regarding fibrate use.

Keywords: Cardiovascular disease; Fibrates; High density lipoprotein cholesterol; Metabolic syndrome; Paradoxical high density lipoprotein cholesterol decrease; Peroxisome proliferator-activated receptor; Randomised control trial; Triglycerides.

Figure 1

Chemical structures of fibrates that have been used clinically.

Figure 2

Change in high-density lipoprotein cholesterol following fibrate treatment stratified by pre-treatment high-density lipoprotein cholesterol concentrations in 248 patients (adapted from Ramachandran et al[86]) - permission received via Rightslink. HDL-C: High density lipoprotein cholesterol.

Figure 3

A time line with landmark statin and fibrate randomised control trials (arrows indicate the year of main publication). The fibrate trials are discussed in the review, while the statin trials are only mentioned when relevant. All the statin trials showed that lowering of LDL-C significantly reduced the cardiovascular event chosen as study outcome. 4S: The scandinavian simvastatin survival study; WOSCOPS: West of scotland coronary prevention study; CARE: Cholesterol and recurrent events trial; LIPID: Long-term intervention with pravastatin in ischaemic disease trial; AFCAPS/TexCAPS: Air force/Texas coronary prevention study; HPS: Heart protection study; PROSPER: The prospective study of pravastatin in the elderly at risk; CARDS: Collaborative atorvastatin diabetes study; PROVE-IT: The pravastatin or atorvastatin evaluation and infection therapy trial; IDEAL: The incremental decrease in events through aggressive lipid lowering study; TNT: Treating to new targets trial; SPARCL: The stroke prevention by aggressive reduction in cholesterol levels trial; JUPITER: Justfication for the use of stains in primary prevention: An intervention trial evaluating rosuvastatin trial.