Combining a statin with a fibrate versus fibrate monotherapy: efficacious but safe?

Statins (hydroxy-methyl-glutaryl-coenzyme reductase inhibitors) remain the cornerstone of lipid-lowering therapy based on the evidence of clinical outcome trials. However, management of dyslipidemia in clinical practice may require the use of other hypolipidemic agents in combination with statins. Fibrate (agonist of peroxisome proliferator-activated receptor-α, PPR-α) monotherapy is effective for the treatment of hypertriglyceridemia, while the combination of a fibrate with a statin is an option in the management of patients with combined dyslipidemia and diabetes mellitus who present with atherogenic dyslipidemia (low high-density lipoprotein (HDL) cholesterol and elevated triglyceride levels). There is evidence that the combination treatment is efficacious towards a global improvement of the lipid abnormalities with a safety profile similar to that of fibrate monotherapy with regard to liver and muscle toxicity. Nevertheless, renal function may be more commonly affected in those treated with a 'fibrate plus statin'. This concern has been raised with fibrate use either alone or in combination with a statin and should be taken into consideration when starting fibrate treatment while the pathophysiological basis and clinical implications of this drug-related effect need further investigation.