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’)10.30895/2312-7821-2023-366safetyrisk-366Research ArticleДОКЛИНИЧЕСКИЕ И КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯPRECLINICAL AND CLINICAL STUDIESТерапия ингибиторами PCSK9 как альтернатива при непереносимости статиновPCSK9 Inhibitor Therapy as an Alternative for Statin Intolerancehttps://orcid.org/0000-0002-0630-4238ШнайдерК. О.ShnaiderK. O.

Шнайдер Ксения Олеговна

ул. Островитянова, д. 1, Москва, 117997

Ksenia O. Shnaider

1 Ostrovityanova St., Moscow 117997

ks.shnaider@mail.ruhttps://orcid.org/0000-0002-8979-8084МаксимовМ. Л.MaximovM. L.

Максимов Максим Леонидович, д-р мед. наук, профессор

ул. Островитянова, д. 1, Москва, 117997

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

ул. Бутлерова, д. 36, Казань, 420012, Республика Татарстан

Maxim L. Maximov, Dr. Sci. (Med.), Professor

1 Ostrovityanova St., Moscow 117997

2/1/1 Barrikadnaya St., Moscow 125993

36 Butlerov St., Kazan 420012, Republic of Tatarstan

maksim_maksimov@mail.ruhttps://orcid.org/0000-0002-4675-9034БарановаВ. А.BaranovaV. A.

Баранова Валерия Алексеевна

ул. Островитянова, д. 1, Москва, 117997

Valeria A. Baranova

1 Ostrovityanova St., Moscow 117997

baranova2002@yandex.ruhttps://orcid.org/0009-0008-0620-238XНекипеловаА. А.NekipelovaA. A.

Некипелова Алена Александровна

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

Alyona A. Nekipelova

8/2 Petrovsky Blvd, Moscow 127051

nekipelovaaa@expmed.ruФедеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияN.I. Pirogov Russian National Research Medical UniversityRussian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской Федерации; Федеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации; Казанская государственная медицинская академия — филиал федерального государственного бюджетного образовательного учреждения дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской ФедерацииРоссияN.I. Pirogov Russian National Research Medical University; Russian Medical Academy of Continuous Professional Education; Kazan State Medical Academy, Branch Campus of the Russian Medical Academy of Continuous Professional EducationRussian FederationФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202329092023114442449Copyright © Шнайдер К.О., Максимов М.Л., Баранова В.А., Некипелова А.А., 20232023Шнайдер К.О., Максимов М.Л., Баранова В.А., Некипелова А.А.Shnaider K.O., Maximov M.L., Baranova V.A., Nekipelova A.A.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/366Актуальность

Актуальность. Основной причиной сердечно-сосудистых патологий является атеросклероз, развивающийся на фоне расстройств липидного обмена, в частности накопления холестерина липопротеидов низкой плотности. Основными препаратами с наибольшей доказательной базой в комплексной терапии дислипидемий являются статины, однако их использование ограничивается непереносимостью у определенной части пациентов. Как альтернатива терапии статинами могут использоваться ингибиторы пропротеиновой конвертазы субтилизин/кексин типа 9 (PCSK9).

Цель

Цель. Анализ возможности применения ингибиторов PCSK9 у пациентов с непереносимостью статинов.

Обсуждение

Обсуждение. Проведенный анализ данных литературы показал, что наиболее частыми проявлениями непереносимости статинов являются мышечные симптомы. Основные механизмы развития статин-ассоциированных осложнений опосредованы ингибированием ГМГ-КоА-редуктазы, а также влиянием препаратов на клеточные и субклеточные процессы, на скелетные мышцы и генетическими особенностями пациентов. Ингибиторы PCSK9 имеют принципиально иной механизм действия — связывают и инактивируют белок PCSK9, что приводит к снижению в крови уровня холестерина липопротеидов низкой плотности. Для препаратов этой группы выявлено небольшое количество нежелательных реакций, наиболее важной из которых является иммуногенность. Однако даже в случае наличия у пациентов антител к ингибитору PCSK9 эффективность препарата относительно снижения уровня липопротеидов низкой плотности остается высокой.

Выводы

Выводы. Применение ингибиторов PCSK9, таким образом, является эффективной, хорошо переносимой и относительно безопасной терапевтической стратегией в лечении гиперлипидемий у пациентов с непереносимостью статинов.

Scientific relevance

Scientific relevance. The main cause of cardiovascular pathologies is atherosclerosis, which is secondary to lipid metabolism disorders, in particular, the accumulation of low-density lipoprotein (LDL) cholesterol. Dyslipidaemia treatment with the largest evidence base predominantly includes statins in combination therapy, but their use is limited by into lerance in some patients. Alternatively, the treatment may include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Aim

Aim. The study aimed to analyse the applicability of PCSK9 inhibitors in patients with statin intolerance.

Discussion

Discussion. According to the literature analysis, the most common presentation of statin intolerance is statin-associated muscle symptoms. The pathogenesis of statin-associated adverse events is mainly mediated by HMGCoA reductase inhibition, treatment effects on cellular and subcellular processes and skeletal muscles, and patients’ genetic makeup. The mechanism of action of PCSK9 inhibitors is entirely different and involves binding and inactivation of the PCSK9 protein, which lowers blood LDL cholesterol levels. PCSK9 inhibitors have been associated with some adverse drug reactions, most notably immunogenicity; however, PCSK9 inhibitors effectively reduce LDL levels even if patients develop antibodies.

Conclusions

Conclusions. Therefore, PCSK9 inhibitors are a safe, well-tolerated, and effec tive therapeutic strategy for hyperlipidaemia in patients with statin intolerance.

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