Update on PPAR agonists: the clinical significance of FIELD and PROACTIVE.

The peroxisome proliferator-activated receptor (PPAR) family of genes plays a major role in metabolic regulation. Unfortunately, the results of two recent, large event trials of PPAR agonists have been mixed. High rates of crossover to statin use confound the interpretation of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, which found a less than expected reduction in coronary and stroke events with fenofibrate. Of concern, nonsignificant increases in coronary and sudden deaths, thrombotic events, and pancreatitis occurred in the fenofibrate group. The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROACTIVE) also found a reduction in coronary and stroke events with pioglitazone compared with placebo in a population with diabetes and cardiovascular disease, but this benefit was counterbalanced by an increase in congestive heart failure as well as symptomatic edema. Further research is needed to determine the role of PPAR agonists in the prevention of cardiovascular disease.