inovmedИнновационная медицина КубаниInnovative Medicine of Kuban2541-9897Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 110.35401/2541-9897-2024-9-2-124-128inovmed-854Research ArticleОБЗОРЫREVIEWSПерспективы применения PCSK-9-модифицирующих агентов при остром коронарном синдромеProspects of Using PCSK9 Inhibitors for Acute Coronary Syndromehttps://orcid.org/0000-0002-5866-506XНамитоковА. М.NamitokovA. M.

Намитоков Алим Муратович, к. м. н., заведующий кардиологическим отделением № 2 для больных с инфарктом миокарда, Научно-исследовательский институт – Краевая клиническая больница №1 им. С.В. Очаповского; доцент кафедры терапии №1ФПК и ППС, Кубанский государственный медицинский университет

350086, Краснодар, ул. 1 Мая, 167

Alim M. Namitokov, Cand. Sci. (Med.), Head of Cardiology Unit No. 2 for Patients with Myocardial Infarction, Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 1; Associate Professor at Therapy Department No. 1, Faculty of Continuing Professional Development and Retraining, Kuban State Medical University

ulitsa 1 Maya 167, Krasnodar, 350086

apakella@mail.ruhttps://orcid.org/0000-0003-3883-8696ЗафиракиВ. К.ZafirakiV. K.

Зафираки Виталий Константинович, д. м. н., профессор кафедры терапии № 1 ФПК и ППС

Краснодар

Vitaliy K. Zafiraki, Dr. Sci. (Med.), Professor at Therapy Department No. 1, Faculty of Continuing Professional Development and Retraining

Krasnodar

https://orcid.org/0000-0002-1543-2987КарабахциеваК. В.KarabakhtsievaK. V.

Карабахциева Карина Витальевна, ординатор кафедры терапии № 1 ФПК и ППС

Краснодар

Karina V. Karabakhtsieva, Resident, Therapy Department No. 1, Faculty of Continuing Professional Development and Retraining

Krasnodar

Научно-исследовательский институт – Краевая клиническая больница №1 им. С.В. Очаповского; Кубанский государственный медицинский университетРоссияScientific Research Institute – Ochapovsky Regional Clinical Hospital No. 1; Kuban State Medical UniversityRussian FederationКубанский государственный медицинский университетРоссияKuban State Medical UniversityRussian Federation20243006202402124128Copyright © Намитоков А.М., Зафираки В.К., Карабахциева К.В., 20242024Намитоков А.М., Зафираки В.К., Карабахциева К.В.Namitokov A.M., Zafiraki V.K., Karabakhtsieva K.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.innovmedkub.ru/jour/article/view/854

Пропротеиновая конвертаза субтилизин-кексин типа 9 представляет собой фермент, участвующий в регуляции уровня холестерина крови путем связывания и разрушения рецепторов липопротеина низкой плотности. Опорные исследования показали, что ингибирования данной молекулы с помощью моноклональных антител алирокумаба и эволокумаба, а также малой интерферирующей РНК инклисирана снижает риск сердечно-сосудистых заболеваний у лиц с ишемической болезнью сердца. Однако место этих препаратов в лечении пациентов с острым коронарным синдромом не определено. В статье обсуждаются исследования по добавлению к терапии PCSK-9-модифицирующих агентов в острый период инфаркта миокарда, а также патофизиологические предпосылки для их применения.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme involved in the regulation of blood cholesterol levels by binding to low-density lipoprotein receptors and promoting their degradation. Pivotal studies have shown that PCSK9 inhibition by monoclonal antibodies, alirocumab and evolocumab, and the small interfering RNA (inclisiran) reduces the risk of cardiovascular diseases in individuals with coronary heart disease. However, the place of the PCSK9 inhibitors in treatment of patients with acute coronary syndrome has not been determined yet. The article discusses studies on the addition of PCSK9 inhibitors to therapy during the acute phase of myocardial infarction as well as pathophysiological prerequisites for their use.

инфаркт миокардаPCSK-9 ингибиторыинклисиранатеротромбозmyocardial infarctionPCSK9 inhibitorsinclisiranatherothrombosisИсследование проведено при поддержке Кубанского научного фонда в рамках научного проекта № МФИ-20.1/63.The study was supported by the Kuban Science Foundation under scientific project No. МФИ-20.1/63.ReferencesRoth GA, Mensah GA, Johnson CO, et al; GBD-NHLBIJACC Global Burden of Cardiovascular Diseases Writing Group. Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982–3021. Published correction appears in J Am Coll Cardiol. 2021;77(15):1958–1959. PMID: 33309175. PMCID: PMC7755038. https://doi.org/10.1016/j.jacc.2020.11.010Roth GA, Mensah GA, Johnson CO, et al; GBD-NHLBIJACC Global Burden of Cardiovascular Diseases Writing Group. Global burden of cardiovascular diseases and risk factors, 1990- 2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982–3021. Published correction appears in J Am Coll Cardiol. 2021;77(15):1958–1959. PMID: 33309175. PMCID: PMC7755038. https://doi.org/10.1016/j.jacc.2020.11.010Chow CK, Islam S, Bautista L, et al. Parental history and myocardial infarction risk across the world: the INTERHEART study. J Am Coll Cardiol. 2011;57(5):619–627. PMID: 21272754. https://doi.org/10.1016/j.jacc.2010.07.054Chow CK, Islam S, Bautista L, et al. Parental history and myocardial infarction risk across the world: the INTERHEART study. J Am Coll Cardiol. 2011;57(5):619–627. PMID: 21272754. https://doi.org/10.1016/j.jacc.2010.07.054Seidah NG, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003;100(3):928–933. PMID: 12552133. PMCID: PMC298703. https://doi.org/10.1073/pnas.0335507100Seidah NG, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003;100(3):928–933. PMID: 12552133. PMCID: PMC298703. https://doi.org/10.1073/pnas.0335507100Almontashiri NA, Vilmundarson RO, Ghasemzadeh N, et al. Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies. PLoS One. 2014;9(9):e106294. PMID: 25180781. PMCID: PMC4152257. https://doi.org/10.1371/journal.pone.0106294Almontashiri NA, Vilmundarson RO, Ghasemzadeh N, et al. Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies. PLoS One. 2014;9(9):e106294. PMID: 25180781. PMCID: PMC4152257. https://doi.org/10.1371/journal.pone.0106294Burchardt P, Rzeźniczak J, Dudziak J, et al Evaluation of plasma PCSK9 concentrations, transcript of LDL receptor, as well as the total number of monocyte LDL receptors in acute coronary syndrome patients. Cardiol J. 2016;23(6):604–609. PMID: 27665855. https://doi.org/10.5603/CJ.a2016.0068Burchardt P, Rzeźniczak J, Dudziak J, et al Evaluation of plasma PCSK9 concentrations, transcript of LDL receptor, as well as the total number of monocyte LDL receptors in acute coronary syndrome patients. Cardiol J. 2016;23(6):604–609. PMID: 27665855. https://doi.org/10.5603/CJ.a2016.0068Fyfe T, Baxter RH, Cochran KM, Booth EM. Plasma-lipid changes after myocardial infarction. Lancet. 1971;2(7732):997–1001. PMID: 4108108. https://doi.org/10.1016/s0140-6736(71)90322-9Fyfe T, Baxter RH, Cochran KM, Booth EM. Plasma-lipid changes after myocardial infarction. Lancet. 1971;2(7732):997–1001. PMID: 4108108. https://doi.org/10.1016/s0140-6736(71)90322-9Navarese EP, Kolodziejczak M, Winter MP, et al. Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: the PCSK9-REACT study. Int J Cardiol. 2017;227:644–649. PMID: 27810295. https://doi.org/10.1016/j.ijcard.2016.10.084Navarese EP, Kolodziejczak M, Winter MP, et al. Association of PCSK9 with platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor: the PCSK9- REACT study. Int J Cardiol. 2017;227:644–649. PMID: 27810295. https://doi.org/10.1016/j.ijcard.2016.10.084Schwartz GG, Steg PG, Szarek M, et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(2):2097–2107. PMID: 30403574. https://doi.org/10.1056/NEJMoa1801174Schwartz GG, Steg PG, Szarek M, et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(2):2097–2107. PMID: 30403574. https://doi.org/10.1056/NEJMoa1801174Sabatine MS, Giugliano RP, Keech AC, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722. PMID: 28304224. https://doi.org/10.1056/NEJMoa1615664Sabatine MS, Giugliano RP, Keech AC, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722. PMID: 28304224. https://doi.org/10.1056/NEJMoa1615664Khan SA, Naz A, Qamar Masood M, Shah R. Meta-analysis of inclisiran for the treatment of hypercholesterolemia. Am J Cardiol. 2020;134:69–73. PMID: 32892993. https://doi.org/10.1016/j.amjcard.2020.08.018Khan SA, NazA, Qamar Masood M, Shah R. Meta-analysis of inclisiran for the treatment of hypercholesterolemia. Am J Cardiol. 2020;134:69–73. PMID: 32892993. https://doi.org/10.1016/j. amjcard.2020.08.018Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/ PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(24):e285–e350. Published correction appears in J Am Coll Cardiol. 2019;73(24):3237–3241. PMID: 30423393. https://doi.org/10.1016/j.jacc.2018.11.003Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/ PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(24):e285–e350. Published correction appears in J Am Coll Cardiol. 2019;73(24):3237–3241. PMID: 30423393. https://doi.org/10.1016/j.jacc.2018.11.003Mach F, Baigent C, Catapano AL, et al; ESC Scientific Document Group. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. Published correction appears in Eur Heart J. 2020;41(44):4255. PMID: 31504418. https://doi.org/10.1093/eurheartj/ehz455Mach F, Baigent C, Catapano AL, et al; ESC Scientific Document Group. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. Published correction appears in Eur Heart J. 2020;41(44):4255. PMID: 31504418. https://doi.org/10.1093/eurheartj/ehz455Li S, Peng Y, Wang X, et al Cardiovascular events and death after myocardial infarction or ischemic stroke in an older Medicare population. Clin Cardiol. 2019;42(3):391–399. PMID: 30697776. PMCID: PMC6712383. https://doi.org/10.1002/clc.23160Li S, PengY, Wang X, et al Cardiovascular events and death after myocardial infarction or ischemic stroke in an older Medicare population. Clin Cardiol. 2019;42(3):391–399. PMID: 30697776. PMCID: PMC6712383. https://doi.org/10.1002/clc.23160Abtan J, Bhatt DL, Elbez Y, et al; REACH Registry Investigators. Residual ischemic risk and its determinants in patients with previous myocardial infarction and without prior stroke or TIA: insights from the REACH Registry. Clin Cardiol. 2016;39(11):670–677. PMID: 27588731. PMCID: PMC6490735. https://doi.org/10.1002/clc.22583Abtan J, Bhatt DL, Elbez Y, et al; REACH Registry Investigators. Residual ischemic risk and its determinants in patients with previous myocardial infarction and without prior stroke or TIA: insights from the REACH Registry. Clin Cardiol. 2016;39(11):670–677. PMID: 27588731. PMCID: PMC6490735. https://doi.org/10.1002/clc.22583Murphy A, Hamilton G, Andrianopoulos N, et al; Melbourne Interventional Group. One-year outcomes of patients with established coronary artery disease presenting with acute coronary syndromes. Am J Cardiol. 2019;123(9):1387–1392. PMID: 30797559. https://doi.org/10.1016/j.amjcard.2019.01.037Murphy A, Hamilton G, Andrianopoulos N, et al; Melbourne Interventional Group. One-year outcomes of patients with established coronary artery disease presenting with acute coronary syndromes. Am J Cardiol. 2019;123(9):1387–1392. PMID: 30797559. https://doi.org/10.1016/j.amjcard.2019.01.037Chen H, Chen X. PCSK9 inhibitors for acute coronary syndrome: the era of early implementation. Front Cardiovasc Med. 2023;10:1138787. PMID: 37200976. PMCID: PMC10185746. https://doi.org/10.3389/fcvm.2023.1138787Chen H, Chen X. PCSK9 inhibitors for acute coronary syndrome: the era of early implementation. Front Cardiovasc Med. 2023;10:1138787. PMID: 37200976. PMCID: PMC10185746. https://doi.org/10.3389/fcvm.2023.1138787Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients with Acute Coronary Syndromes (EVOPACS). J Am Coll Cardiol. 2019;74(20):2452–2462. PMID: 31479722. https://doi.org/10.1016/j.jacc.2019.08.010Koskinas KC, Windecker S, Pedrazzini G, et al. Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients with Acute Coronary Syndromes (EVOPACS). J Am Coll Cardiol. 2019;74(20):2452–2462. PMID: 31479722. https://doi.org/10.1016/j.jacc.2019.08.010Mehta SR, Pare G, Lonn EM, et al. Effects of routine early treatment with PCSK9 inhibitors in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a randomised, double-blind, sham-controlled trial. EuroIntervention. 2022;18(11):e888–e896. PMID: 36349701. PMCID: PMC9743253. https://doi.org/10.4244/EIJ-D-22-00735Mehta SR, Pare G, Lonn EM, et al. Effects of routine early treatment with PCSK9 inhibitors in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a randomised, double-blind, sham-controlled trial. EuroIntervention. 2022;18(11):e888–e896. PMID: 36349701. PMCID: PMC9743253. https://doi.org/10.4244/EIJ-D-22-00735Trankle CR, Wohlford G, Buckley LF, et al. Alirocumab in acute myocardial infarction: results from the Virginia Commonwealth University Alirocumab Response Trial (VCU-AlirocRT). J Cardiovasc Pharmacol. 2019;74(3):266–269. PMID: 31356537. PMCID: PMC8336145. https://doi.org/10.1097/FJC.0000000000000706Trankle CR, Wohlford G, Buckley LF, et al. Alirocumab in acute myocardial infarction: results from the Virginia Commonwealth University Alirocumab Response Trial (VCU-AlirocRT). J Cardiovasc Pharmacol. 2019;74(3):266–269. PMID: 31356537. PMCID: PMC8336145. https://doi.org/10.1097/FJC.0000000000000706Räber L, Ueki Y, Otsuka T, et al; PACMAN-AMI collaborators. Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction: the PACMAN-AMI randomized clinical trial. JAMA. 2022;327(18):1771–1781. PMID: 35368058. PMCID: PMC8978048. https://doi.org/10.1001/jama.2022.5218Räber L, Ueki Y, Otsuka T, et al; PACMAN-AMI collaborators. Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction: the PACMAN-AMI randomized clinical trial. JAMA. 2022;327(18):1771–1781. PMID: 35368058. PMCID: PMC8978048. https://doi.org/10.1001/jama.2022.5218Zanchin C, Koskinas KC, Ueki Y, et al. Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-rationale and design of the PACMAN-AMI trial. Am Heart J. 2021;238:33–44. PMID: 33951415. https://doi.org/10.1016/j.ahj.2021.04.006Zanchin C, Koskinas KC, Ueki Y, et al. Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-rationale and design of the PACMAN-AMI trial. Am Heart J. 2021;238:33–44. PMID: 33951415. https://doi.org/10.1016/j.ahj.2021.04.006Nicholls SJ, Kataoka Y, Nissen SE, et al. Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction. JACC Cardiovasc Imaging. 2022;15(7):1308–1321. PMID: 35431172. https://doi.org/10.1016/j.jcmg.2022.03.002Nicholls SJ, Kataoka Y, Nissen SE, et al. Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction. JACC Cardiovasc Imaging. 2022;15(7):1308–1321. PMID: 35431172. https://doi.org/10.1016/j.jcmg.2022.03.002Zhang Y, Suo Y, Yang L, et al. Effect of PCSK9 inhibitor on blood lipid levels in patients with high and very-high CVD risk: a systematic review and meta-analysis. Cardiol Res Pract. 2022;2022:8729003. PMID: 35529059. PMCID: PMC9072011. https://doi.org/10.1155/2022/8729003Zhang Y, Suo Y, Yang L, et al. Effect of PCSK9 inhibitor on blood lipid levels in patients with high and very-high CVD risk: a systematic review and meta-analysis. Cardiol Res Pract. 2022;2022:8729003. PMID: 35529059. PMCID: PMC9072011. https://doi.org/10.1155/2022/8729003

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