safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2023-11-3-292-302safetyrisk-385Research ArticleГЛАВНАЯ ТЕМА: СОВРЕМЕННАЯ ГИПОЛИПИДЕМИЧЕСКАЯ ТЕРАПИЯ: НЕ ТОЛЬКО СТАТИНЫMAIN TOPIC: CURRENT LIPID-LOWERING THERAPY: STATINS AND MOREЭффективность и безопасность бемпедоевой кислоты как нового гиполипидемического средстваBempedoic Acid: Safety and Efficiacy of a New Lipid-Lowering Agenthttps://orcid.org/0000-0002-3733-6822МазеркинаИ. А.MazerkinaI. A.

Мазеркина Ирина Анатольевна - кандидат медицинских наук.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Irina A. Mazerkina - Cand. Sci. (Med.).

8/2 Petrovsky Blvd, Moscow 127051

mazerkina@expmed.ruhttps://orcid.org/0000-0002-7597-2926БукатинаТ. М.BukatinaT. V.

Букатина Татьяна Михайловна - кандидат медицинских наук.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Tatiana M. Bukatina - Cand. Sci. (Med.).

8/2 Petrovsky Blvd, Moscow 127051

bukatina@expmed.ruhttps://orcid.org/0000-0003-3855-5899АлександроваТ. В.AleksandrovaT. V.

Александрова Татьяна Владимировна - кандидат медицинских наук.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Tatiana V. Alexandrova - Cand. Sci. (Med.).

8/2 Petrovsky Blvd, Moscow 127051

aleksandrova@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202326092023113292302Copyright © Мазеркина И.А., Букатина Т.М., Александрова Т.В., 20232023Мазеркина И.А., Букатина Т.М., Александрова Т.В.Mazerkina I.A., Bukatina T.V., Aleksandrova T.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/385Актуальность

Актуальность. Применение статинов для снижения уровня холестерина липопротеидов низкой плотности (ХС-ЛПНП) является общепринятым стандартом терапии дислипидемий. Но развитие нежелательных реакций и непереносимости статинов стимулировало поиск липидомодифицирующих средств с альтернативными механизмами действия, одним из которых является бемпедоевая кислота.

Цель

Цель. Обзор данных литературы по механизму действия, фармакокинетике, фармакодинамике, эффективности и безопасности бемпедоевой кислоты как гиполипидемического средства.

Обсуждение

Обсуждение. Бемпедоевая кислота является лекарственным средством, которое аналогично статинам подавляет синтез холестерина из ацетил-коэнзима А. Выявлено, что главным отличием механизма действия бемпедоевой кислоты является образование ее активного метаболита только в печени, поэтому она не вызывает мышечных нежелательных реакций. Основные данные по эффективности и безопасности бемпедоевой кислоты получены в клинических исследованиях III фазы CLEAR: бемпедоевая кислота в комбинации с максимально переносимыми дозами статинов дополнительно снижала уровень ХС-ЛПНП на 18%, а при монотерапии у пациентов с непереносимостью статинов — на 25% по сравнению с плацебо. Длительное применение бемпедоевой кислоты у пациентов с непереносимостью статинов в исследовании CLEAR Outcomes (n=13970) показало снижение риска развития сердечно-сосудистых осложнений на 13%. Применение бемпедоевой кислоты было ассоциировано с небольшим повышением частоты приступов подагры, как правило, у пациентов с гиперурикемией.

Выводы

Выводы. Применение бемпедоевой кислоты является эффективным и безопасным вариантом лечения дислипидемии у пациентов с высоким риском атеросклеротических сердечно-сосудистых заболеваний как в комбинации с липидоснижающей терапией статинами, так и в качестве монотерапии или в комбинации с эзетимибом при непереносимости статинов.

Scientific relevance

Scientific relevance. Lowering low-density lipoprotein cholesterol (LDL-C) levels with statins is a generally accepted standard treatment for dyslipidaemia. However, adverse reactions and intolerance to statins have motivated the search for lipid-modifying agents with alternative mechanisms of action. Bempedoic acid is one of these alternative agents.

Aim

Aim. The study aimed to review published data on the mechanism of action, pharmacokinetics, pharmacodynamics, safety and efficacy of bempedoic acid used as a lipid-lowering agent.

Discussion

Discussion. Similar to statins, bempedoic acid inhibits cholesterol synthesis from acetyl-CoA. Statins and bempedoic acid differ in their mechanisms of action mainly because the conversion of bempedoic acid into its active metabolite takes place only in the liver. As a result, bempedoic acid does not cause adverse drug reactions in muscles. The main safety and efficacy data on bempedoic acid were obtained in phase III CLEAR trials. Compared to placebo, bempedoic acid reduced LDL-C levels by an additional 18% in combination with maximum tolerated doses of statins and by 25% in monotherapy in patients with statin intolerance. In the CLEAR Outcomes trial, long-term treatment with bempedoic acid reduced the risk of major adverse cardiovascular events in patients with statin intolerance (n=13970) by 13%. A slight increase in gout attack frequency was observed, primarily in patients with pre-existing hyperuricaemia.

Conclusions

Conclusions. Therefore, bempedoic acid is a safe and effective treatment option for patients with dyslipidaemia at high risk of atherosclerotic cardiovascular disease. It can be used either in combination with statins or, in the case of statin intolerance, as monotherapy and with ezetimibe.

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The authors declare that there are no conflicts of interest present.