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’)10.30895/2312-7821-2023-11-3-252-270safetyrisk-391Research ArticleГЛАВНАЯ ТЕМА: СОВРЕМЕННАЯ ГИПОЛИПИДЕМИЧЕСКАЯ ТЕРАПИЯ: НЕ ТОЛЬКО СТАТИНЫMAIN TOPIC: CURRENT LIPID-LOWERING THERAPY: STATINS AND MOREСтатин-индуцированная миопатияStatin-Induced Myopathyhttps://orcid.org/0000-0002-4496-3680СычевД. А.SychevD. A.

Сычев Дмитрий Алексеевич - академик РАН, доктор медицинских наук, профессор.

Ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Dmitry A. Sychev - Academician of the Russian Academy of Sciences, Dr. Sci. (Med.), Professor.

2/1/1 Barrikadnaya St., Moscow 1125993

rmapo@rmapo.ruhttps://orcid.org/0000-0003-4258-1889ОстроумоваТ. М.OstroumovaT. M.

Остроумова Татьяна Максимовна - кандидат медицинских наук.

Ул. Трубецкая, д. 8, стр. 2, Москва, 119991

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

8/2 Trubetskaya St., Moscow 119991

t.ostroumova3@gmail.comhttps://orcid.org/0000-0002-0795-8225ОстроумоваО. Д.OstroumovaO. D.

Остроумова Ольга Дмитриевна - доктор медицинских наук, профессор.

Ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993; Ул. Трубецкая, д. 8, стр. 2, Москва, 119991

Olga D. Ostroumova - Dr. Sci. (Med.), Professor.

2/1/1 Barrikadnaya St., Moscow 1125993; 8/2 Trubetskaya St., Moscow 119991

ostroumova.olga@mail.ruhttps://orcid.org/0000-0001-5801-3742КочетковА. И.KochetkovA. I.

Кочетков Алексей Иванович - кандидат медицинских наук, доцент

Ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Aleksey I. Kochetkov - Cand. Sci. (Med.), Associate Professor.

2/1/1 Barrikadnaya St., Moscow 1125993

ak_info@list.ruhttps://orcid.org/0000-0003-1316-7654БатюкинаС. В.BatyukinaS. V.

Батюкина Светлана Владимировна

Ул. Баррикадная, д. 2/1, стр. 1, Москва, 125993

Svetlana V. Batyukina

2/1/1 Barrikadnaya St., Moscow 1125993

Batyukina.svetlana@yandex.ruhttps://orcid.org/0000-0002-2988-1767МироноваЕ. В.MironovaE. V.

Миронова Елена Владимировна - кандидат медицинских наук.

Волоколамское шоссе, д. 84, Москва, 125367

Elena V. Mironova - Cand. Sci. (Med.).

84 Volokolamsk Hwy, Moscow 125367

e.v.mironova@mail.ruФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет им. И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФедеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет им. И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияRussian Medical Academy of Continuous Professional Education; I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationЧастное учреждение здравоохранения «Центральная клиническая больница “РЖД-Медицина”»РоссияCentral Clinical Hospital “RZD-Medicine”,Russian Federation202326092023113252270Copyright © Сычев Д.А., Остроумова Т.М., Остроумова О.Д., Кочетков А.И., Батюкина С.В., Миронова Е.В., 20232023Сычев Д.А., Остроумова Т.М., Остроумова О.Д., Кочетков А.И., Батюкина С.В., Миронова Е.В.Sychev D.A., Ostroumova T.M., Ostroumova O.D., Kochetkov A.I., Batyukina S.V., Mironova E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/391Актуальность

Актуальность. Статины как основной класс препаратов для коррекции дислипидемий у различных категорий пациентов исключительно широко применяются в клинической практике. Вместе с тем данные препараты способны вызывать статин-ассоциированные мышечные симптомы (САМС) — наиболее частую нежелательную реакцию на фоне статинотерапии, которая в ряде случаев может достигать степени тяжести, угрожающей жизни пациента.

Цель

Цель. Систематизация сведений, касающихся эпидемиологии САМС, их классификации, патофизиологических механизмов развития, факторов риска и практических рекомендаций для врачей первичного звена по выявлению и тактике ведения пациентов с данным осложнением фармакотерапии.

Обсуждение

Обсуждение. САМС — собирательный термин, объединяющий различные варианты миопатий при статинотерапии. Показано, что распространенность САМС существенно различается по данным имеющихся публикаций и, вероятно, зависит от дизайна исследования, критериев включения и рассматриваемого препарата.

Предполагаемые механизмы развития САМС многообразны и включают, в частности, генетически детерминированные процессы, нарушения в функционировании митохондрий, дефекты внутриклеточных сигнальных и метаболических путей, а также иммуноопосредованные реакции. К основным известным факторам риска САМС относятся применяемая высокая доза статинов, межлекарственные взаимодействия, генетические полиморфизмы, женский пол, пожилой возраст, азиатская раса, заболевания почек, печени, мышц в анамнезе, тяжелые физические нагрузки. Общепризнанные алгоритмы диагностики САМС в настоящее время отсутствуют, вместе с тем для выявления данной нежелательной реакции клиницисту необходимо учитывать характер клинической картины и наличие временной связи между терапией препаратами и дебютом симптомов. Важную роль также играет динамика уровня миоспецифических ферментов, а ряде случаев — данные серологического исследования крови на антитела к 3-гидрокси-3-метил-глутарил-кофермент А редуктазе.

Выводы

Выводы. Для обеспечения безопасности фармакотерапии статинами важную роль играет повышение информированности клиницистов о факторах риска, клинических и лабораторно-инструментальных признаках САМС, а также о необходимости динамического контроля состояния пациентов, в том числе с привлечением врачей — клинических фармакологов.

Scientific relevance

Scientific relevance. Being the main class of medicinal products for dyslipidaemia treatment, statins are widely used in clinical practice in various patient populations. However, statins can cause statin-associated muscle symptoms (SAMS), which are the most frequent and, in some cases, even life-threatening adverse reactions associated with these medicinal products.

Aim

Aim. The study aimed to perform a systematic review of the epidemiology, classification, and physiological pathogenesis of SAMS, risk factors for this complication, and clinical guidelines for primary care physicians regarding the identification and treatment of patients with SAMS.

Discussion

Discussion. SAMS is an umbrella term that covers various forms of myopathies associated with satin therapy. According to the published literature, the prevalence of SAMS varies considerably and may depend on the study design, inclusion criteria, and the medicinal product used. SAMS has multiple putative pathogenic pathways that include genetically determined processes, abnormalities in mitochondrial function, defects in intracellular signalling and metabolic pathways, and immune-mediated reactions. The main known risk factors for developing SAMS include high-dose statins, drug–drug interactions, genetic polymorphisms, female sex, older age, Asian race, history of kidney, liver, and muscle disease, and strenuous physical activity. Given the lack of universally recognised algorithms for diagnosing SAMS, clinicians should consider the clinical presentation and the temporal relationship between statin therapy and symptoms. Other factors to consider include changes in muscle-specific enzyme levels and, in some cases, the results of blood tests for antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.

Conclusions

Conclusions. To ensure the safety of statin therapy, it is essential to raise clinicians’ awareness of the risk factors for SAMS, indicative clinical and laboratory findings, and the need for dynamic patient monitoring, including the involvement of clinical pharmacologists.

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