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Bempedoic Acid in the Treatment of Patients with Dyslipidemias and Statin Intolerance

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Abstract

An elevated plasma low-density lipoprotein cholesterol (LDL-C) level is a well-established atherosclerotic cardiovascular disease (ACSVD) risk factor. Randomized studies with statins (alone or in combination with other lipid-lowering drugs) have demonstrated their clinical efficacy in lowering LDL-C. Several classes of new, non-statin agents have been successfully studied and used (e.g., ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 [i-PSCK9]). However, many high ACSVD risk patients remain at a high residual cardiovascular risk, with at least 10% being statin intolerant. Bempedoic acid (ETC-1002) is a new inhibitor of cholesterol synthesis that targets ATP citrate lyase (ACL). Importantly, ETC-1002 is only converted into an active form in the liver and is free of muscle side effects.

Area Covered: Mechanism of action of ETC-1002, clinical pharmacology, completed clinical studies with bempedoic acid, lipid-lowering efficacy/safety issues, and recent meta-analyses of trials with ETC-1002.

Expert Opinion: ETC-1002 has been extensively studied in phase I–III clinical studies in over 4000 individuals from different patient populations (statin intolerance, familial hypercholesterolemia, and high ACSVD risk patients), ETC-1002 has been demonstrated to have moderate cholesterol-lowering efficacy and a good safety profile at a dose of 180 mg/day as a monotherapy and in combination with statins and ezetimibe. The ongoing study CLEAR Outcomes, with composite cardiovascular endpoints, will elucidate the role of bempedoic acid in the management of high ACSVD risk and statin-intolerant patients with hypercholesterolemia. Long-term safety data on bempedoic acid are needed to fully establish this agent in evidence-informed guidelines for managing of patients with dyslipidemias.

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Authors and Affiliations

  1. GBOU DPO Russian Medical Academy for Postgraduate Medical Education Ministry of Health, Moscow, Russian Federation

    Andrey V. Susekov

  2. I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation

    Ludmila A. Korol

  3. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia

    Gerald F. Watts

  4. Lipid Disorders Clinic, Cardiometabolic Service, Departments of Cardiology and Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia

    Gerald F. Watts

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Contributions

Andrey V Susekov: literature search, first draft of manuscript and lead editor of manuscript.

Ludmila A Korol: literature search, writing a segment on clinical pharmacology.

Gerald F Watts: general plan of writing overview, paper proof-reading and correction, writing a segment on clinical trials.

Proof-reading complete: 16 July 2020 by Proof-reading Services Ltd. UK.

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English language (US) editing completed 20 Оct 2020 by Scribendi (http:// www.scribendi.com).

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Correspondence to Andrey V. Susekov.

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Conflicts of Interest/Competing Interests

Andrey V Susekov: none for this manuscript.

Lecturer, honoraria: AstraZeneca, Abbott, KRKA, Akrikhin, Sanofi-Aventis, Amgen, Servier. Teva Pharmaceuticals. Clinical Trials: ESPERION 2018–2019, PI (Clear OUTCOMES), KOWA Research (PROMINENT, K-877-301, K-877-302).

Ludmila A Korol: none.

Gerald Watts: GFW has received honoraria for advisory boards and research grants from Amgen, Arrowhead, Gemphire, Kowa, Novartis, Pfizer, Sanofi and Regeneron.

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Susekov, A.V., Korol, L.A. & Watts, G.F. Bempedoic Acid in the Treatment of Patients with Dyslipidemias and Statin Intolerance. Cardiovasc Drugs Ther 35, 841–852 (2021). https://doi.org/10.1007/s10557-020-07139-x

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