Peroxisome proliferator-activated receptor (PPAR) -α belongs to the nuclear family of ligand-activated transcriptional
factors. The main role of PPAR-α is to activate the expression of the genes that are involved in fatty acid oxidation
to achieve energy homeostasis. Fibrates are a known class of PPAR-α agonists, and they been used clinically for
their effects of lowering triglycerides and elevating high-density lipoprotein-cholesterol (HDL-C). Further, recent
experimental studies have demonstrated the anti-inflammatory and anti-atherosclerotic actions of PPAR-α agonists
directly on the vascular wall. PPAR agonists are currently emerging as a promising therapeutic option to
control systemic and vascular atherogenic factors. Regardless of their strong anti-atherosclerotic properties, large
clinical studies have demonstrated inconsistent results for the cardioprotective effect of PPAR-α agonists; moreover,
it has been observed that they did not decrease the total mortality, which stands in contrast to the statin trials.
This review summarizes the current knowledge regarding the PPAR biology and the mechanisms of the effects of
PPAR-α on lipid metabolism, the vessel wall and the cardiac metabolism. We also describe the results and lessons
learned from the important clinical trials of PPAR-α agonists and we discuss these drugs’ efficacy and safety.