Ezetimibe therapy: mechanism of action and clinical update

• Published in: Vascular health and risk management 2012-01, Vol.8 (default), p.415-427
• Main Authors: Phan, Binh An P, Dayspring, Thomas D, Toth, Peter P
• Format: Article
• Language: English
• Subjects: Animals; Anticholesteremic Agents - adverse effects; Anticholesteremic Agents - therapeutic use; Azetidines - adverse effects; Azetidines - therapeutic use; bile; Biomarkers - blood; Cholesterol; coronary artery disease; Dyslipidemias - blood; Dyslipidemias - drug therapy; Ezetimibe; Humans; Intestinal Absorption - drug effects; Jejunum - drug effects; Jejunum - metabolism; Lipids - blood; Low density lipoproteins; low-density lipoprotein cholesterol; Nieman pick C1 like 1 protein; Review; statin; Statins; Treatment Outcome
• ISSN: 1178-2048; 1176-6344; 1178-2048
• DOI: 10.2147/vhrm.s33664

The lowering of low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy in the primary and secondary prevention of cardiovascular events. Although statin therapy is the mainstay for LDL-C lowering, a significant percentage of patients prescribed these agents either do not achieve targets with statin therapy alone or have partial or complete intolerance to them. For such patients, the use of adjuvant therapy capable of providing incremental LDL-C reduction is advised. One such agent is ezetimibe, a cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border. Its primary target of action is the cholesterol transport protein Nieman Pick C1 like 1 protein. Ezetimibe is an effective LDL-C lowering agent and is safe and well tolerated. In response to significant controversy surrounding the use and therapeutic effectiveness of this drug, we provide an update on the biochemical mechanism of action for ezetimibe, its safety and efficacy, as well as the results of recent randomized studies that support its use in a variety of clinical scenarios.