An Update on Statin Alternatives and Adjuncts

Matthew J Sorrentino


Clin Lipidology. 2012;7(6):721-730. 

In This Article


The fibrates are a class of medications that are agonists of PPAR-α. The PPARs are nuclear transcription factors that modulate gene expression with effects on lipid and glucose metabolism. PPAR-α agonists lower triglyceride levels and mildly raise HDL-C with minimal change or a slight increase in LDL-C levels. This increase in LDL-C may be due to an increase in particle size and, thus, the cholesterol content of the LDL particles, and not an absolute increase in the number of LDL particles. Fibrates are mainly used as triglyceride-lowering agents and may be useful in individuals with mixed hyperlipidemia.

Gemfibrozil has been studied in both primary and secondary prevention trials. The VA-HIT compared 1200 mg of gemfibrozil with placebo in over 2500 men with coronary heart disease and low HDL-C levels.[49] Gemfibrozil caused an increase in HDL-C levels by 6%, lowered triglycerides by 31% and caused no change in LDL-C. There was a 24% reduction in the combined end point of death from coronary disease, nonfatal myocardial infarction and stroke. Patients with metabolic syndrome or diabetes (high triglycerides and low HDL-C) seemed to derive the most benefit from therapy with gemfibrozil.[50] This study suggests that patients with a mixed hyperlipidemia who cannot tolerate statins may obtain cardiovascular risk reduction using fibrates.

It is less clear if combining a fibrate with a statin can give further risk reduction. The ACCORD study compared the combination of simvastatin plus fenofibrate with simvastatin alone and failed to show any further cardiovascular risk reduction with combination therapy.[51]