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Cholesterol Absorption Inhibitor Ezetimibe: Risk–Benefits and Role in Treating Dyslipidemias

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Dyslipidemias

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Ezetimibe, a novel lipid-lowering compound, selectively inhibits intestinal cholesterol absorption by binding to Niemann-Pick C1-Like 1 (NPC1L1). Ezetimibe reduces the hepatic influx of cholesterol via chylomicron remnants, enhances the hepatic expression of low-density lipoproteins (LDL) receptor, and thus reducing LDL-cholesterol (LDL-C) levels. Ezetimibe also attenuates the development of atherosclerosis in various animal models. The administration of ezetimibe decreases the fasting levels of LDL-C in patients with primary hypercholesterolemia as well as plant sterols in patients with sitosterolemia. A significantly greater reduction in LDL-C levels is achieved in patients treated with ezetimibe plus statin combination compared with statin monotherapy.

Ezetimibe was reported to decrease fasting triglycerides (TG) levels as well as postprandial TG-rich lipoprotein and remnants significantly in patients with combined hyperlipidemia and those with hypertriglyceridemia (TG ≥ 150 mg/dl); however, its underlying mechanism of action on TG-rich lipoprotein metabolism has not yet been elucidated. Ezetimibe administration can attenuate postprandial hyperlipidemia by reducing the production of chylomicrons (CMs) from the small intestines and decreasing the absorption of free fatty acids (FFA).

More recently, ezetimibe has been reported to attenuate nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) in animal models and humans. Since the influx of chylomicron remnants and FFA into the liver is decreased by ezetimibe, it is plausible that it may attenuate hepatic lipid deposition. The antiatherosclerotic effects of ezetimibe have been demonstrated in a variety of animal models and more recently in some clinical trials. In the recent Study of Heart and Renal Protection (SHARP) Trial, the combination of simvastatin and ezetimibe was shown to be effective for major atherosclerotic events in patients with chronic kidney disease. Taken together, ezetimibe may possess additional pleiotropic roles in addition to lipid-lowering effects.

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Acknowledgments

The authors gratefully acknowledge the excellent technical assistance and office work extended by Kaori Hizu-Shioyama, Risa Wada, and Kyoko Ozawa. This work was supported by a Grant-in-Aid for Scientific Research (No. 13671191) to S. Yamashita from the Japanese Ministry of Education, Science, Sports and Culture and in part by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), Foundation for Biomedical Research and Innovation for Akifumi Matsuyama, Daisaku Masuda, Shizuya Yamashita.

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  1. Department of Community Medicine, Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan

    Shizuya Yamashita MD, PhD, FAHA, FJCC

  2. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, 565-0871, Suita, Osaka, Japan

    Daisaku Masuda MD, PhD

  3. Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, 567-0085, Ibaraki, Osaka, Japan

    Akifumi Matsuyama MD, PhD

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  1. Shizuya Yamashita MD, PhD, FAHA, FJCC
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Correspondence to Shizuya Yamashita MD, PhD, FAHA, FJCC .

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  1. Professor of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA

    Abhimanyu Garg

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Yamashita, S., Masuda, D., Matsuyama, A. (2015). Cholesterol Absorption Inhibitor Ezetimibe: Risk–Benefits and Role in Treating Dyslipidemias. In: Garg, A. (eds) Dyslipidemias. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-424-1_28

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