Ezetimibe: cholesterol lowering and beyond

Abstract

Ezetimibe is a cholesterol absorption inhibitor that blocks the intestinal absorption of both biliary and dietary cholesterol. It appears to exert its effect by blocking intestinal sterol transporters, specifically Niemann–Pick C1-like 1 proteins, thereby inhibiting the intestinal absorption of cholesterol, phytosterols and certain oxysterols. Ezetimibe monotherapy and in combination with statin therapy is primarily indicated for lowering LDL-cholesterol levels. In addition, it may favorably affect other parameters that could potentially further reduce atherosclerotic coronary heart disease risk, such as raising HDL-cholesterol and lowering levels of triglycerides, non-HDL-cholesterol, apolipoprotein B and remnant-like particle cholesterol. Further effects of ezetimibe include a reduction in circulating phytosterols and oxysterols and, when used in combination with statins, a reduction in high-sensitivity C-reactive protein. The clinical significance of the LDL-cholesterol lowering and other effects of ezetimibe is being evaluated in clinical outcome studies.

Keywords::

• ezetimibe
• HDL-C
• non-HDL-C
• oxysterols
• phytosterols
• RLP-C

Financial & competing interests disclosure

Harold Bays has served as a Clinical Investigator for (and has received research grants from) pharmaceutical companies such as Abbott, Amylin, Alteon, Arena, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Boehringer Mannheim, Bristol Myers Squibb, Ciba Geigy, Daiichi Sankyo, Eli Lilly, Esperion, Fujisawa, GelTex, Genetech, GlaxoSmithKline, Hoechst Roussel, Hoffman LaRoche, InterMune, KOS, Kowa, Lederle, Marion Merrell Dow, Merck, Merck Schering Plough, Miles, Microbia, Novartis, Obecure, Orexigen, Parke Davis, Pfizer, Pliva, Purdue, Reliant, Roche, Rorer, Regeneron, Sandoz, Sanofi, Sciele, Searle, Shionogi, Schering Plough, SmithKline Beacham, Takeda, TAP, UpJohn, Upsher Smith, Warner Lambert, and Wyeth-Ayerst. He has also served as a consultant, speaker and/or advisor to and for pharmaceutical companies such as Abbott, Arena, AstraZeneca, Aventis, Bayer, Bristol Myers Squibb, Daiichi Sankyo, KOS, Merck, Merck Schering Plough, Metabasis Therapeutics, Microbia, Novartis, Nicox, Ortho-McNeil, Parke Davis, Pfizer, Reliant, Roche, Sandoz, Sanofi Aventis, Schering Plough, SmithKline Beacham, Takeda, UpJohn, and Warner Lambert. Drs Neff, Tershakovec and Tomassini are employees of Merck and own stock and stock options.

No writing assistance was utilized in the production of this manuscript.