title: The ezetimibe controversy: implications for clinical practice.
abstract: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of lipid-lowering therapy. Achieving LDL-C goals as outlined by the National Cholesterol Education Program Adult Treatment Panel III can be difficult with statins alone; therefore, adjunctive therapy is often indicated to reduce cardiovascular risk. Ezetimibe, a potent inhibitor of intestinal cholesterol absorption, has been shown to be safe, tolerable and effective at lowering LDL-C, non-high-density lipoprotein cholesterol and apolipoprotein B, each of which has been correlated with improved clinical outcomes, alone or in combination with a statin. However, because of randomized trials that demonstrated mixed results about atherosclerotic plaque regression via carotid intima-media thickness and a concern about cancer risk, ezetimibe's role in lipid therapy has been questioned. Currently, a large randomized controlled trial is in progress to answer if ezetimibe improves clinical outcomes in patients with high-risk acute coronary syndrome. A smaller trial in patients with chronic kidney disease demonstrated reduced clinical events, including myocardial infarction, stroke and revascularization for patients taking the combination of ezetimibe and simvastatin versus those taking statin or placebo alone. In this paper, we review the trials that have led to the ezetimibe controversy and then discuss the possible role of ezetimibe in specific patient populations until the results of ongoing clinical trials are known.
authors.affiliation: College of Pharmacy and Department of Pharmacy Services, University of Michigan, Ann Arbor, Michigan 48109-5008, USA. shamo@med.umich.edu
authors.forename: Ujjaini
authors.initials: U
authors.lastname: Khanderia
authors.forename: Randolph E
authors.initials: RE
authors.lastname: Regal
authors.forename: Melvyn
authors.initials: M
authors.lastname: Rubenfire
authors.forename: Thomas
authors.initials: T
authors.lastname: Boyden
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000503:physiopathology; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects*; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D009369:Neoplasms / Q000139:chemically induced / Q000209:etiology; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000473:pathology
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe