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Fibrates should not be used as first line lipid-lowering drugs for primary or secondary prevention of cardiovascular disease. So say the MHRA and CHM in the most recent issue of Drug Safety Update (4th November 2007). This follows a risk-benefit review which found only limited data to support a long term clinical benefit from fibrates in these indications. Given the robust evidence for statins for primary and secondary prevention the use of fibrates as a first-line treatment is no longer justified in these indications.
Fibrates should be used as first-line therapy only in patients with isolated severe hypertriglyceridaemia. In patients with mixed hyperlipidaemia, fibrates should be considered only when a statin or other effective treatments are contraindicated or not tolerated. In patients with primary hypercholesterolaemia, gemfibrozil may be considered but again only when a statin or other effective treatments are contraindicated or not tolerated.
Some clinical guidelines recommend a combination of a statin with a fibrate when statin therapy alone has not reduced triglycerides and/or increased HDL-C to target levels. However, there is no robust evidence of long-term clinical benefit from this approach. Combination of a statin and a fibrate increases the risk of myopathy and rhabdomyolysis. The MHRA/CHM say this combination should be used with caution, and only when expected benefits outweigh potential risks. In particular, gemfibrozil should not be used with a statin.
Only two trials, both with gemfibrozil, out of the five fibrate RCTs assessed showed a statistically significant reduction in non-fatal cardiovascular events in patients given fibrates. Most trials showed an overall negative effect on mortality, with slightly more deaths in patients given fibrates compared with control group. The most recent study of fenofibrate, in patients with type two diabetes (the FIELD study) showed no significant benefit from fenofibrate treatment in this population.
You can find more information on management of hyperlipidaemia, including an analysis of the FIELD study and the rest of the evidence base for fibrates, and the arguments for and against lipid targets, on the lipids section of NPC
Drug Safety Update replaces Current Problems in Pharmacovigilance. If you would like to receive an e-mail notification when new issues of Drug Safety Update are published, please subscribe to the MHRA’s free e-mail alerting service