Abstract

Ezetimibe, an inhibitor of intestinal cholesterol absorption, can decrease total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TGs) and apolipoprotein (apo) B levels and increase high-density lipoprotein cholesterol (HDL-C) levels. Apart from lipid-lowering, ezetimibe may exert certain off-target actions (e.g. anti-inflammatory, anti-atherogenic and antioxidant) thus contributing to a further decrease of cardiovascular disease (CVD) risk.

Ezetimibe trials resulted in controversial outcomes with some studies reporting atherosclerosis regression and reductions in CVD events following ezetimibe therapy in combination with a statin while others reported negative results. The results of the ongoing IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) which compares ezetimibe plus simvastatin with simvastatin monotherapy with regard to CVD outcomes after acute coronary syndromes should further elucidate the effect of ezetimibe on CVD events.

This review presents the results of up-to-date clinical trials with ezetimibe and summarizes its potential pleiotropic effects. Furthermore, we comment on the administration of ezetimibe in treating high-risk patients [i.e. with diabetes mellitus (DM), metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), peripheral artery disease (PAD) or carotid disease]. The use of ezetimibe either as monotherapy or as add-on therapy in daily clinical practice is also discussed.

Keywords: Ezetimibe, clinical trials, dyslipidemia, pleiotropic actions, drug combinations, cholesterol.