Intensification of lipid-lowering therapy in patients with acute coronary syndrome

Lipid metabolism disorders play a key role in determining cardiovascular risk. The level of low-density lipoprotein cholesterol is a significant factor in the pathophysiology of atherosclerosis and an indicator, the assessment of which reduces the risk of cardiovascular events. The prevalence of acute coronary syndrome in Russia remains at a high level. To date, the successful implementation and implementation of standards for the management of acute coronary syndrome has significantly reduced hospital mortality rates, however, secondary prevention issues remain relevant. Despite a wide range of lipid-lowering drugs, the use of which at maximum doses in acute coronary syndrome does not allow reaching the target levels of the lipid spectrum, the risk of developing repeated cardiovascular events remains high. Recently, a promising direction is the use of type 9 subtilisin/ kexin proprotein convertase inhibitors for the intensification of lipid-lowering therapy in patients with acute coronary syndrome. This article presents the clinical case of the successful use of one of the inhibitors of the proprotein convertase of subtilisin/kexin type 9, alirocoumab, in lowering low-density lipoprotein cholesterol and thereby reducing the risk of repeated cardiovascular events in a patient with acute coronary syndrome.

dyslipidemia, acute coronary syndrome, PCSK9 inhibitors, statins, alirocoumab

1. Гарганеева А.А., Округин С.А., Ефимова Е.В., Борель К.Н. «Регистр острого инфаркта миокарда» как информационная популяционная система оценки эпидемиологической ситуации и медицинской помощи больным острым инфарктом миокарда. Сердце. 2013; 1 (12): 37-41.

2. Барбараш О.Л., Кашталап В.В. Контроль липидов у пациентов после перенесенного инфаркта миокарда — эффективный инструмент управления сердечно-сосудистым риском. Атеротромбоз. 2017; 1: 94-104. doi.org/10.21518/2307-1109-2017-1-94-104

3. Piepoli M.F., Hoes A.W., Agewall S., Albus C., Brotons C., Catapano A.L., Cooney M.T., Corrà U., Cosyns B., Deaton C., Catapano A.L., Cooney M.T., Corrà U., Cosyns B., Deaton C., Graham I., Hall M.S., Hobbs F.D.R. Løchen M.L., Löllgen H., Marques-Vidal P., Perk J., Prescott E., Redon J., Richter D.J., Sattar N., Smulders Y., Tiberi M., van der Worp H.B., van Dis I., Verschuren W.M.M., Binno S.; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). European Heart Journal. 2016; 37: 2315-2381. doi:10.1093/eurheartj/ehw106

4. Yusuf S., Hawken S., Ounpuu S., Dans T., Avezum A., Lanas F., McQueen M., Budaj A., Pais P., Varigos J., Lisheng L.; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study) case-control study. Lancet. 2004; (364): 937–952. doi:10.1016/S01406736(04)17018-9

5. Ежов М.В., Сергиенко И.В., Кухарчук В.В., Карпов Ю.А., Бубнова М.Г., Гуревич В.С. и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза: Российские рекомендации, VI пересмотр. Атеросклероз и дислипидемии. – 2017. – №3. – С. 5–22.

6. Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., Chapman M.J., De Backer G.G., Delgado V., Ference B.A., Graham I.M., Halliday A., Landmesser U., Mihaylova B., Pedersen T.R., Riccardi G., Richter D.J., Sabatine M.S., Taskinen M.R., Tokgozoglu L., Wiklund O.; ESC Scientific Document Group. 2019 ESC/ EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020 Jan 1;41(1):111-188. doi:10.1093/eurheartj/ehz455.

7. Moriarty P.M., Parhofer K.G., Babirak S.P., Cornier M.A., Duell P.B., Hohenstein B., Leebmann J., Ramlow W., Schettler V., Simha V., Steinhagen-Thiessen E., Thompson P.D., Vogt A., von Stritzky B., Du Y., Manvelian G. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J. 2016; 37(48):3588-3595. doi:10.1093/eurheartj/ehw388.

8. Stroes E., Guyton J.R., Lepor N., Civeira F., Gaudet D., Watts G.F., Baccara-Dinet M.T., Lecorps G., Manvelian G., Farnier M. Efficacy and safety of alirocumab 150 mg every 4 weeks in patients with hypercholesterolemia not on statin therapy: the ODYSSEY CHOICE II study. J Am Heart Assoc. 2016; 5 (9): e003421. doi:10.1161/JAHA.116.003421.

9. Careskey H.E., Davis R.A., Alborn W.E. Troutt J.S., Cao G., Konrad R.J. .Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res. 2008; 49: 394–398. doi:10.1194/jlr.M700437-JLR200

10. Welder G., Zineh I., Pacanowski M.A., Troutt J.S., Cao G., Konrad R.J. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res. 2010; 51: 2714–2721. doi:10.1194/jlr.M008144.

11. Okada K., Iwahashi N., Endo T., Himeno H, Fukui K., Kobayashi S. et al. Long-term effects of ezetimibe-plusstatin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease. Atherosclerosis. 2012; 224: 454–456. doi:10.1016/j.atherosclerosis.2012.07.036.

12. Попова А.Б., Нозадзе Д.Н., Сергиенко И.В. Роль PCSK9 в генезе развития сердечно-сосудистых заболеваний. Атеросклероз и дислипидемии. 2016; 3: 5-14.

13. Kereiakes D.J., Robinson J.G., Cannon C.P., Lorenzato C, Pordy R., Chaudhari U., Colhoun H.M. Efficacy and safety of the proproteinconvertasesubtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J. 2015; 169 (6): 906-915.e13. doi:10.1016/j.ahj.2015.03.004.

14. Cannon C.P., Cariou B., Blom D., McKenney J.M., Lorenzato C., Pordy R., Chaudhari U., Colhoun H.M.; ODYSSEY COMBO II Investigators.Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015; 36 (19): 1186-94. doi:10.1093/eurheartj/ehv028.

15. Карпов Ю.А. Ингибиторы PCSK9 в улучшении прогноза у пациентов после острого коронарного синдрома: данные исследования ODYSSEY OUTCOMES. Рациональная Фармакотерапия в Кардиологии 2018; 14 (6): 922-934. DOI:10.20996/1819-6446-2018-14-6-922-934

16. Navarese E.P., Kolodziejczak M., Kereiakes D.J., Tantry U.S., O’Connor C., Gurbel P.A. Proprotein convertase subtilisin/kexin type 9 antibodies for acute coronary syndrome: a narrative review. Ann Intern Med 2016; 164 (9): 600–607. doi:10.7326/M15-2994.

17. Сорокин Е.В., Карпов Ю.А. Алирокумаб – представитель нового класса гиполипидемических препаратов. Атмосфера. Новости кардиологии. 2016; 3: 23-28.