Plasma uric acid concentrations are reduced by fenofibrate: A systematic review and meta-analysis of randomized placebo-controlled trials

Abstract

Background

Hyperuricaemia increases the risk of gout, but it is also a risk factor for cardiovascular diseases.

Purpose

To conduct a systematic review and meta-analysis of relevant randomized clinical trials to ascertain the effect size of fibrates in modulating plasma uric acid concentrations.

Data sources

Medline (http://www.ncbi.nlm.nih.gov/pubmed), SCOPUS, Web of Science and Google Scholar databases were searched.

Study selection

Studies were included if they met the following inclusion criteria: (i) being a randomized placebo-controlled trial with either parallel or cross-over design, (ii) investigating the impact of fibrate therapy on plasma uric acid concentrations, (iii) presentation of sufficient information on uric acid values at baseline and at the end of follow-up in each group or providing the net change values.

Data extraction

The following data were extracted: (1) first author’s name; (2) year of publication; (3) study location; (4) study design; (5) number of participants in the fibrate and placebo groups; (6) type and dose of fibrate; (7) duration of treatment; (8) age, gender and body mass index (BMI) of study participants; (9) baseline levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, high-sensitivity C-reactive protein (hs-CRP) and glucose; (10) systolic and diastolic blood pressure; and (11) data regarding baseline and follow-up uric acid.

Data synthesis

There was a significant reduction in plasma uric acid concentrations following fenofibrate therapy.

Limitations

Few eligible studies, and most had small population sizes.

Conclusions

Fenofibrate, but not bezafibrate is effective in reducing serum acid uric levels.

Introduction

Serum uric acid is the final product of purine metabolism in humans. Hyperuricaemia increases the risk of gout, but it has also been addressed as a possible risk factor for cardiovascular disease [1], [2]. Hyperuricaemia can accelerate atherosclerosis and increase oxidative stress and endothelial dysfunction [3], [4]. Moreover, patients with gout often have metabolic co-morbidities including visceral fat obesity, hypertension, hyperlipidaemia, and impaired glucose tolerance [5], [6]. Dietary and pharmacological urate-lowering therapies principally aim to prevent joint damage. Allopurinol, an inhibitor of xanthine oxidase, is the most frequently used drug in the treatment of hyperuricaemia, and is usually well tolerated and lowers serum urate in the order of 20% [7]. Febuxostat is a newer, orally administered, non-purine analogue inhibitor of xanthine oxidase. Febuxostat is a potent xanthine oxidase inhibitor, has minimal effects on other enzymes involved in purine and pyrimidine metabolism, and it is metabolized mainly by glucuronide formation and oxidation in the liver [8], [9].

In recent years, it has been reported that some drugs used to treat dyslipidaemia like fibrates could play a possible role in decreasing serum concentration of uric acid via an enhanced urinary excretion of uric acid [10]. Fibrates act via activation of the nuclear transcription factor peroxisome proliferator activated receptor-α (PPAR-α), predominantly expressed in liver, kidney, heart and muscle. Among fibrates, their action on lipid profile is well known [11], for example fenofibrate seems to produce significantly greater reductions in total cholesterol, LDL, and triglycerides, as well as significantly greater increases in HDL than gemfibrozil [12]. However, fibrates’ effects on hyperuricaemia are not so well established and findings of randomized controlled trials (RCTs) have not been conclusive. Hence, the aim of the present study was to conduct a systematic review and meta-analysis of relevant RCTs in order to ascertain the effect size of fibrates in modulating plasma uric acid concentrations.