cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.2022.6.n2115cardio-2115Research ArticleОБЗОРЫREVIEWSИнклисиран – новая эра в гиполипидемической терапииInclisiran – a new era in lipid-lowering therapyhttps://orcid.org/0000-0001-9425-413XВоеводаМ. И.VoevodaM. I.

Директор, академик, д.м.н., профессор

Director, Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor.

mvoevoda@ya.ruГуревичВ. С.GurevichV. S.

Руководитель Центра по лечению атеросклероза и нарушений липидного обмена, профессор, заведующий отделом атеросклероза научно-клинического и образовательного Центра

Head of the Center for the Treatment of Atherosclerosis and Lipid Metabolism Disorders, Professor, Head of the Atherosclerosis Department of the Scientific, Clinical and Educational Center

vktrgurevich@gmail.comЕжовМ. В.EzhovM. V.

доктор медицинских наук, профессор, главный научный сотрудник отдела проблем атеросклероза, руководитель лаборатории нарушений липидного обмена

Doctor of Medical Sciences, Professor, Chief Researcher of the Department of Atherosclerosis Problems, Head of the Laboratory of Lipid Metabolism Disorders

marat_ezhov@mail.ruСергиенкоИ. В.SergienkoI. V.

Профессор, доктор медицинских наук, старший научный сотрудник 

Professor, Doctor of Medical Sciences, Senior Researcher

igorcardio@mail.ruФГБНУ "Федеральный исследовательский центр фундаментальной и трансляционной медицины", НовосибирскРоссияFederal Research Center of Fundamental and Translational Medicine, NovosibirskRussian FederationФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова», Минздрава России, Санкт-ПетербургRussian FederationMechnikov North-Western State Medical University, St. PetersburgRussian FederationФГБУ «Национальный медицинский исследовательский центр кардиологии им. Е.И. Чазова», Минздрава России, МоскваRussian FederationChazov National Medical Research Center of Cardiology, MoscowRussian Federation2022300620226265762Copyright © Kardiomag, 20222022KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/2115

Инклисиран – новый гиполипидемический препарат, ингибирующий синтез белка PCSK9 с помощью процесса, называемого «РНК-интерференция», и представляющий собой двухцепочечную модифицированную РНК, связанную с углеводной молекулой N-ацетилгалактозамина (GalNAc) – лигандом асиалогликопротеинового рецептора, экспрессирующегося гепатоцитами. Попадая в гепатоциты, инклисиран вызывает расщепление матричной РНК и соответствующее снижение синтеза белка PCSK9. В свою очередь это приводит к усилению захвата циркулирующих липопротеидов низкой плотности (ЛНП) специфическими рецепторами гепатоцитов и соответственно к снижению их концентрации в крови. Эффективность и безопасность применения инклисирана для снижения концентрации холестерина (ХС) ЛНП в крови и влияния на риск развития кинических осложнений атеросклероза были изучены и изучаются в рамках программы ORION, включающей большое число клинических исследований. По результатам выполнения программы в настоящее время показано, что инклисиран эффективно снижает уровень ХС ЛНП и частоту развития сердечно-сосудистых осложнений в отсутствие клинически значимых неблагоприятных реакций. Важным преимуществом инклисирана по сравнению с другими липидснижающими препаратами является режим его введения – 2 раза в год, позволяющий значительно повысить приверженность пациентов к лечению и эффективность гиполипидемической терапии.

 

Inclisiran is a novel hypolipidemic drug that inhibits synthesis of the PCSK9 protein through the process called RNA interference. Inclisiran is a double-stranded, modified RNA bound to the N-acetylgalactosamine (GalNAc) carbohydrate molecule, a ligand of the acialoglycoprotein receptor, that is expressed by hepatocytes. After entering hepatocytes, inclisiran cleaves matrix RNA and, thereby, reduces the PCSK9 protein synthesis. This, in turn, enhances the uptake of circulating low-density lipoproteins (LDL) by specific receptors on hepatocytes, thereby lowering LDL levels in circulation. Efficacy and safety of inclisiran for lowering LDL cholesterol (C) in blood and its effect on the risk of clinical complications of atherosclerosis have been studied in the ORION program that includes multiple clinical trials. According to results of this program, inclisiran effectively reduces both LDL-C levels and the incidence of cardiovascular complications in the absence of clinically significant adverse reactions. An important advantage of inclisiran compared with other lipid-lowering drugs is the administration schedule (twice a year), which allows a considerable improvement of patients’ compliance with the treatment and also of the effectiveness of the hypolipidemic treatment.

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