Ezetimibe: a selective cholesterol absorption inhibitor

Abstract

Ezetimibe is the first agent of a novel class of selective cholesterol absorption inhibitors recently approved by the Food and Drug Administration for treatment in the United States. Ezetimibe inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids. Ezetimibe localizes at the brush border of the small intestine and decreases cholesterol uptake into the enterocytes. Preclinical studies demonstrated lipid-lowering properties of ezetimibe as monotherapy and showed a synergistic effect in combination with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). The efficacy and safety of ezetimibe 10 mg/day have been established in phase III clinical trials. In these trials, ezetimibe was investigated as monotherapy, as an add-on to ongoing statin therapy, and as combination therapy with statins in patients with primary hypercholesterolemia. In addition, ezetimibe has been evaluated in patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia. When given as monotherapy or in combination with statins or fenofibrate, ezetimibe reduces low-density lipoprotein cholesterol (LDL) by 15-20% while increasing high-density lipoprotein cholesterol by 2.5-5%. Unlike other intestinally acting lipid-lowering agents, ezetimibe does not adversely affect triglyceride levels and, due to its minimal systemic absorption, drug interactions are few. Ezetimibe's side-effect profile resembles that of placebo when given as monotherapy or in combination with statins. In clinical practice, ezetimibe has a role as monotherapy for patients who require modest LDL reductions or cannot tolerate other lipid-lowering agents. In combination therapy with a statin, ezetimibe is used in patients who cannot tolerate high statin doses or in those who need additional LDL reductions despite maximum statin doses.