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Efficacy and Safety of Lomitapide in Hypercholesterolemia

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Abstract

Background

Despite extensive use of statins, patients with hypercholesterolemia, especially homozygous familial hypercholesterolemia (HoFH), do not achieve recommended targets of low-density lipoprotein cholesterol (LDL-C). There is an urgent need for novel options that could reduce proatherogenic lipoprotein cholesterol levels. Lomitapide, a microsomal triglyceride transport protein (MTP) inhibitor, was approved three years ago as an orphan drug for the treatment of patients with HoFH.

Objective

Our aim was to systematically evaluate the efficacy and safety of lomitapide and to provide guidance for clinicians.

Methods

We searched the PubMed, Embase, and Cochrane library databases and ClinicalTrials.gov to identify valid studies published before 31 October 2016 that included lomitapide-treated patients who did or did not undergo lipid-lowering therapy. We assessed the quality of different studies. Data were extracted and evaluated for quality by two reviewers.

Results

Studies reporting lomitapide therapy included one randomized controlled trial, three single-arm studies, and five case reports. In patients with HoFH, lomitapide reduced levels of LDL-C, total cholesterol, apolipoprotein B, and triglycerides with or without other lipid-lowering therapy, including apheresis. In non-HoFH patients with moderate hypercholesterolemia and hypertriglyceridemia, lomitapide also showed favorable effects on changes in LDL-C and triglycerides. However, both HoFH and non-HoFH patients experienced a reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-1). The most common adverse event was gastrointestinal disorder, and others included liver transaminase elevation and hepatic fat accumulation. Long-term use of lomitapide was associated with an increased risk of progressing to steatohepatitis and fibrosis.

Conclusions

Lomitapide improved most lipid parameters but not HDL-C or ApoA-1 in patients with HoFH and in non-HoFH patients, and gastrointestinal disorders were the most common adverse event. The possible benefits of lomitapide should be further evaluated and viewed against its possible long-term side effects.

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Acknowledgements

The authors thank Dr. Xunde Xian of the Department of Molecular Genetics, UT Southwestern Medical Center at Dallas, TX, for advice and suggestions on the manuscript.

Author contributions

George Liu designed the study and revised the manuscript, Xin Liu and Peng Men extracted the data, Yuhui Wang and Suodi Zhai evaluated the studies quality, Suodi Zhai and Zhigang Zhao verified the data. Xin Liu and Peng Men collected the data and composed the manuscript. George Liu and Zhigang Zhao contributed to interpretation of the results, reviewing the draft, and finalizing the manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Xin Liu & Zhigang Zhao

  2. Department of Pharmacy, Peking University Third Hospital, Beijing, China

    Peng Men & Suodi Zhai

  3. Institute of Cardiovascular Sciences, School of Basic Medicine, Peking University Health Science Center, Beijing, China

    Xin Liu, Yuhui Wang & George Liu

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  1. Xin Liu
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Correspondence to Zhigang Zhao or George Liu.

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Conflict of interest

Xin Liu, Peng Men, Yuhui Wang, Suodi Zhai, Zhigang Zhao, and George Liu have no conflicts of interest that might be relevant to the contents of this manuscript.

Funding

This work was supported by Grants from the National Natural Science Foundation of the People’s Republic of China to G. Liu (No. 81470555) and Y. Wang (No. 81570787).

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Registration number in PROSPERO: CRD42016037302.

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Liu, X., Men, P., Wang, Y. et al. Efficacy and Safety of Lomitapide in Hypercholesterolemia. Am J Cardiovasc Drugs 17, 299–309 (2017). https://doi.org/10.1007/s40256-017-0214-7

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