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Statins and Lomitapide: A Suitable Response for Homozygous Familial Hypercholesterolemia?

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Combination Therapy In Dyslipidemia

Abstract

Autosomal dominant hypercholesterolemia (ADH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth and the occurrence of premature cardiovascular disease and myocardial infarction. ADH is determined by defects in genes encoding for proteins involved in the metabolism of LDL, including LDLR, apolipoprotein B, and PCSK9. Carrying these mutations results in the exposure to high levels of LDL-C from birth and the onset of premature cardiovascular disease. Among the various forms of ADH, familial hypercholesterolemia caused by mutations in the LDLR gene in the homozygous form (HoFH) is the most severe. If untreated, these subjects have a severely impaired life expectancy; thus, lipid-lowering therapies are recommended to start very early to delay the onset of cardiovascular disease. Unfortunately, often HoFHs do not respond adequately to classical cholesterol-lowering drugs, especially subjects carrying mutations that drastically reduce the expression of hepatic LDLR. Thus, the need to find out new drugs directed to different targets led to the development of lomitapide, an inhibitor of microsomal triglyceride transfer protein (MTP), an enzyme playing a key role in the biosynthesis of VLDL and chylomicrons. Lomitapide significantly reduces LDL-C levels in HoFH subjects, either as monotherapy or in association with current lipid-lowering therapies; VLDL-C, triglycerides, total cholesterol, and apoB are also reduced. Lomitapide is generally well tolerated, gastrointestinal manifestations, transient hepatic enzyme elevation, and modest increase of hepatic fat being the most common adverse effects. The lipid-lowering efficacy of lomitapide in association with statins may thus represent an effective strategy for the management of HoFH subjects.

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Authors and Affiliations

  1. Center for the Study of Atherosclerosis, E. Bassini Hospital, Via M. Gorki 50, Cinisello Balsamo, Italy

    Angela Pirillo

  2. IRCCS Multimedica, Milan, Italy

    Angela Pirillo & Alberico Luigi Catapano

  3. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy

    Alberico Luigi Catapano

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  1. Angela Pirillo
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  2. Alberico Luigi Catapano
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Correspondence to Angela Pirillo .

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Editors and Affiliations

  1. Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Lodz, Poland

    Maciej Banach

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Pirillo, A., Catapano, A.L. (2015). Statins and Lomitapide: A Suitable Response for Homozygous Familial Hypercholesterolemia?. In: Banach, M. (eds) Combination Therapy In Dyslipidemia. Adis, Cham. https://doi.org/10.1007/978-3-319-20433-8_8

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  • DOI: https://doi.org/10.1007/978-3-319-20433-8_8

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-20432-1

  • Online ISBN: 978-3-319-20433-8

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