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Cholesterol absorption inhibition: filling an unmet need in lipid-lowering management

E. Leitersdorf*

Department of Medicine, Hadassah University Hospital, Jerusalem, Israel

* Correspondence: Eran Leitersdorf, MD, Center for Research, Prevention and Treatment of Atherosclerosis, Department of Medicine, Hadassah University Hospital, P.O. Box 12-221, Jerusalem, 91120, Israel.

Abstract

International guidelines specify target concentrations of low-density lipoprotein cholesterol (LDL-C) to reduce the risk of coronary heart disease. Although statins are the most widely prescribed cholesterol-lowering drugs, they have a number of limitations. A significant number of statin-treated patients do not reach recommended LDL-C target levels, even with high-dose therapy. Each doubling of the statin dose results in only a 6% reduction in LDL-C. Elevation of liver transaminase levels and muscle toxicity have been associated with high statin doses. Currently available agents that are co-administered with statins are not well tolerated due to gastrointestinal intolerance or are associated with an increased risk of myopathy. The limitations of statin monotherapy and currently available combination therapy warrant the need for more safe, effective and convenient approaches to combination therapy. Co-administration of statins and cholesterol absorption inhibitors may overcome some of these limitations and effectively target both the endogenous and exogenous pathways of cholesterol metabolism. Ezetimibe, a novel selective cholesterol absorption inhibitor, has demonstrated an excellent safety and tolerability profile and a LDL-C-lowering effect that is additive with statins. Co-administration of ezetimibe and a statin may therefore fill an unmet need in lipid-lowering management and provide broader lipid control.

Key Words: Cholesterol absorption inhibitor • ezetimibe • statins • hypercholesterolaemia • low-density lipoprotein cholesterol • target cholesterol levels


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