avkАрхивъ внутренней медициныThe Russian Archives of Internal Medicine2226-67042411-6564“SINAPS” LLC10.20514/2226-6704-2018-8-4-266-276avk-805Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESПОБОЧНЫЕ ЭФФЕКТЫ СТАТИНОВ: МЕХАНИЗМЫ РАЗВИТИЯ, ДИАГНОСТИКА, ПРОФИЛАКТИКА И ЛЕЧЕНИЕSTATIN ADVERSE EFFECTS: MECHANISMS, DIAGNOSIS, PREVENTION AND MANAGEMENTДядыкА. И.DyadykA. I.

кафедра терапии ФИПО,

Донецк

Department of Therapy, Faculty of postgraduated education, 

Donetsk

КуглерТ. Е.KuglerT. E.

кафедра терапии ФИПО,

Донецк

Department of Therapy, Faculty of postgraduated education, 

Donetsk

kugler2@mail.ruСулиманЮ. В.SulimanY. V.

кафедра терапии ФИПО,

Донецк

Department of Therapy, Faculty of postgraduated education, 

Donetsk

ЗборовскийС. Р.ZborovskyyS. R.

кафедра терапии ФИПО,

Донецк

Department of Therapy, Faculty of postgraduated education, 

Donetsk

ЗдиховскаяИ. И.ZdykhovskayaI. I.

кафедра терапии ФИПО,

Донецк

Department of Therapy, Faculty of postgraduated education, 

Donetsk

Донецкий Национальный медицинский университет им. Максима ГорькогоУкраинаM. Gorky Donetsk National Medical UniversityUkraine20181108201884266276Copyright © Дядык А.И., Куглер Т.Е., Сулиман Ю.В., Зборовский С.Р., Здиховская И.И., 20182018Дядык А.И., Куглер Т.Е., Сулиман Ю.В., Зборовский С.Р., Здиховская И.И.Dyadyk A.I., Kugler T.E., Suliman Y.V., Zborovskyy S.R., Zdykhovskaya I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medarhive.ru/jour/article/view/805

Статины являются одними из наиболее распространенных гиполипидемических препаратов в клинической практике. Целью данно го обзора было систематизировать наиболее частые побочные эффекты статинов, представив механизмы их развития, диагностику, тактику лечения и профилактику. По данным реестров и наблюдательных исследований частота развития статин-ассоциированных мышечных симптомов значительно выше, чем в рандомизированных контролируемых исследованиях. Диагностика клинических проявлений мышечных симптомов затруднена, так как часто базируется на субъективной оценке больного и врача. При этом плазменные уровни креатинкиназы нередко остаются в пределах нормы или незначительно повышенными. В многочисленных исследованиях также продемонстрировано наличие ассоциации между применением статинов и развитием сахарного диабета. Стойкое и существенное повышение уровня трансаминаз часто обусловлено взаимодействием статинов с другими лекарственными препаратами, применением высоких дозировок и наличием сопутствующих заболеваний. Перед назначением статинов необходимо проведение базисных гликемических тестов, определение уровня печеночных трансаминаз и креатинкиназы для выявления пациентов с высоким риском развития побочных эффектов. Неоднозначны результаты ряда рандомизированных контролируемых исследований о риске развития геморрагических инсультов при проведении статиновой терапии. Предполагается, что статины могут ингибировать канцерогенез путем индукции апоптоза или ингибирования роста клеток, ангиогенеза и инвазии. Однако результаты доклинических и клинических исследований противоречат друг другу. Большинство исследований, посвященных изучению эффективности статинов и их побочных эффектов, являются наблюдательными или ретроспективными, в связи с чем, существует необходимость в проведении более крупных проспективных рандомизированных плацебо-контролируемых исследований с длительным периодом наблюдения. Врачу любой специальности требуется знать потенциальные негативные последствия применения статинов, учитывая расширение показаний к их применению. Понимание фармакокинетики статинов имеет первостепенное значение для обеспечения безопасности пациентов. Необходимо учитывать дозировки, пути метаболизма и факторы риска развития лекарственного взаимодействия с целью минимизации побочных эффектов статинов.

Statins are one of the most common lipid-lowering drugs in clinical practice. The purpose of this review was to systemize the most frequent statin adverse effects, including mechanisms, diagnosis, treatment and prevention. The frequency of statin-associated muscle symptoms is significantly higher in registries and observational studies than in randomized controlled trials. Diagnosis of muscle symptoms is difficult because it is subjective. The serum creatine kinase is often normal or slightly elevated. Association between statin use and the risk of new cases of diabetes mellitus was demonstrated in numerous studies. The drug interaction of statins, high dosage and concomitant diseases can lead to a persistent and clinically significant increase of hepatic enzymes. Basic glycemic tests, hepatic enzymes and serum creatine kinase have been necessary done before statin administration to identify patients with high risk of intolerance. The risk of hemorrhagic strokes after statin therapy is ambiguous due to randomized controlled trials. It is suggested that statins can inhibit cancerogenesis by inducing apoptosis or reducing cell growth, angiogenesis, and invasion. However, the results of preclinical and clinical studies are conflicting. The majority of the studies are observational or of retrospective nature. It is necessary to provide a larger prospective randomized placebo-controlled trials with a long follow-up. Any doctor should know the potential negative consequences of statins taking into account their expansion. Understanding the pharmacokinetics of statins is important for the safety of patients. Dosages, metabolism and risk factors of drug interactions should be considered to minimize statin adverse effects.

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