Lipid-lowering drugs: present and future

Abstract

Hyperlipidemia is one of the most important risk factors for the development atherosclerotic cardiovascular diseases. The review summarizes data on lipoprotein metabolism and discusses methods pharmacological correction of dyslipidemia. Classification presented Lipid-lowering drugs, pharmacodynamics and pharmacokinetic features, indications for use and side effects of individual representatives, issues of their effectiveness and safety are considered. Prospects for the treatment of dyslipidemia are outlined.

Keywords

dyslipidemias / treatment / hypolipidemic drugs / statins / fibrates / bempedoic acid

References

[1] Oksenoit GK, Nikitin SY, editors. Health care in Russia. Statistical collection. Moscow: Rosstat; 2017. 170 p. (In Russ.)

[2] Здравоохранение в России. Статистический сборник / под ред. Г.К. Оксенойт, С.Ю. Никитина. Москва: Росстат. 2017. 170 с.

[3] Sergienko IV, Nedogoda CV, Vertkin AL, et al. Actual issues of increasing the availability of innovative therapy and organization of medical care for patients with atherosclerotic cardiovascular diseases in the Russian Federation. Council of experts. Journal of Atherosclerosis and Dyslipidemias. 2022;(49):54–61. (In Russ.) EDN: CVUPPX doi: 10.34687/2219-8202.JAD.2022.04.0006

[4] Сергиенко И.В., Недогода C.В., Верткин А.Л., и др. Актуальные вопросы повышения доступности инновационной терапии и организации медицинской помощи пациентам c атеросклеротическими сердечно-сосудистыми заболеваниями в Российской Федерации. Совет Экспертов // Атеросклероз и дислипидемии. 2022. № 49. С. 54–61. EDN: CVUPPX doi: 10.34687/2219-8202.JAD.2022.04.0006

[5] Golan DE, Armstrong EJ, Armstrong AW, editors. Principles of pharmacology: the pathophysiologic basis of drug therapy: fourth Edition. Elsevier: 2017. P. 1042.

[6] Principles of Pharmacology: the pathophysiologic basis of drug therapy. Fourth edition. Golan D.E., Armstrong E.J., Armstrong A.W. editors. Elsevier, 2017. P. 1042.

[7] Chaulin AM. New groups of hypolipidemic medications based on inhibition of proprotein convertase subtilisin/kexin type 9 (pcsk9). Part 1. Clinical Medicine. 2020;98(11–12):739–744. EDN: JXHPIA doi: 10.30629/0023-2149-2020-98-11-12-12-739-744

[8] Чаулин А.М. Новые группы гиполипидемических препаратов, основанные на ингибировании пропротеиновой конвертазы субтилизин-кексинового типа 9 (PCSK9). Часть 1 // Клиническая медицина. 2020. Т. 98, № 11–12. С. 739–744. EDN: JXHPIA doi: 10.30629/0023-2149-2020-98-11-12-739-744

[9] Borodulin VI, Topoliansky AV. To the scientific results of the twentieth century: the role of domestic researchers in the development of atherosclerosis. Clinical Medicine. 2013;91(11):70–73. (In Russ.) EDN: RSHRUP

[10] Бородулин В.И., Тополянский А.В. К научным итогам ХХ века: роль отечественных исследователей в разработке атеросклероза // Клиническая медицина. 2013. Т. 91, № 11. С. 70–73. EDN: RSHRUP

[11] Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–1681. doi: 10.1016/S0140-6736(10)61350-5

[12] Baigent C., Blackwell L., Emberson J., et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials // Lancet. 2010. Vol. 376, N 9753. P. 1670–1681. doi: 10.1016/S0140-6736(10)61350-5

[13] Karpov YuA. The efficacy and safety of statin therapy. Atmosphere. Cardiology News. 2019;(1):3–12. EDN: GRIGYR

[14] Карпов Ю.А. Эффективность и безопасность терапии статинами // Атмосфера. Новости кардиологии. 2019. № 1. С. 3–12. EDN: GRIGYR

[15] Chaulin AM. The main side effects of statins in clinical practice. Clinical Practice. 2022;13(2):98–107. EDN: QHSXST doi: 10.17816/clinpract108076

[16] Чаулин А.М. Основные побочные эффекты статинов в клинической практике // Клиническая практика. 2022. Т. 13, № 2. С. 98–107. EDN: QHSXST doi: 10.17816/clinpract108076

[17] Makhatova AR, Tuleutaeva RE. Dangerous and undesirable drug interactions of statins in patients with cardiovascular disease. Science & Health Care. 2019;21(2):55–56. EDN: ZKVNBB

[18] Махатова А.Р., Тулеутаева Р.Е. Опасные и нежелательные межлекарственные взаимодействия статинов у больных кардиоваскулярной патологией // Наука и здравоохранение. 2019. T. 21, № 2. С. 55–56. EDN: ZKVNBB

[19] Sumarokov AB, Kukharchuk VV. Hypolipidemic and pleiotropic effects of a combination of simvastatin and ezetimibe in patients with different types of hyperlipidemia. Therapeutic Archive. 2014;86(12): 107–115. EDN: RNYIIS doi: 10.17116/terarkh20148612107-115

[20] Сумароков А.Б., Кухарчук В.В. Гиполипидемические и плейотропные эффекты комбинации симвастатина и эзетимиба у больных различными видами гиперлипидемий // Терапевтический архив. 2014. Т. 86, № 12. С. 107–115. EDN: RNYIIS doi: 10.17116/terarkh20148612107-115

[21] Lawitz EJ, Bhandari BR, Ruane PJ, et al. Fenofibrate mitigates hypertriglyceridemia in nonalcoholic steatohepatitis patients treated with cilofexor/firsocostat. Clin Gastroenterol Hepatol. 2023;21(1): 143–152.e3. doi: 10.1016/j.cgh.2021.12.044

[22] Lawitz E.J., Bhandari B.R., Ruane P.J., et al. Fenofibrate mitigates hypertriglyceridemia in nonalcoholic steatohepatitis patients treated with cilofexor/firsocostat // Clin Gastroenterol Hepatol. 2023. Vol. 21, N 1. P. 143–152.e3. doi: 10.1016/j.cgh.2021.12.044.

[23] Shaposhkin AI, Genkel VV. Pleiotropic effects of ezetimibe. Cardiology. 2019;59(12):12–17. EDN: ZIIFEL doi: 10.18087/cardio.n875

[24] Шапошкин И.И., Генкель В.В. Плейотропные эффекты эзетимиба // Кардиология. 2019. Т. 59, № 12. С. 12–17. EDN: ZIIFEL doi: 10.18087/cardio.n875

[25] Gurevich VS, Solodovnikov AG, Manko KS, et al. The efficacy of ezetimibe and statin combination therapy compared to statin monotherapy: a systematic review and meta-analysis of observational trials. Atmosphere. Cardiology News. 2023;(3):33–46. EDN: PFTAPH doi: 10.24412/2076-4189-2023-13015

[26] Гуревич В.С., Солодовников А.Г., Манько К.С., и др. Эффективность комбинации эзетимиба и статинов по сравнению с монотерапией статинами: систематический обзор и метаанализ наблюдательных исследований // Атмосфера. Новости кардиологии. 2023. № 3. С. 33–46. EDN: PFTAPH doi: 10.24412/2076-4189-2023-13015

[27] Robinson JG, Rogers WJ, Nedergaard BS, et al. Rationale and design of LAPLACE-2: a phase 3, randomized, double-blind, placebo- and ezetimibe-controlled trial evaluating the efficacy and safety of evolocumab in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2014;37(4):195–203. doi: 10.1002/clc.22252

[28] Robinson J.G., Rogers W.J., Nedergaard B.S., et al. Rationale and design of LAPLACE-2: a phase 3, randomized, double-blind, placebo- and ezetimibe-controlled trial evaluating the efficacy and safety of evolocumab in subjects with hypercholesterolemia on background statin therapy // Clin Cardiol. 2014. Vol. 37, N 4. P. 195–203. doi: 10.1002/clc.22252

[29] Schneider KO, Maksimov ML, Baranova VA, et al. PCSK9 inhibitor therapy as an alternative for statin intolerance. Safety and Risk of Pharmacotherapy. 2023;11(4):442–449. EDN: OZZYFX doi: 10.30895/2312-7821-2023-366

[30] Шнайдер К.О., Максимов М.Л., Баранова В.А., и др. Терапия ингибиторами PCSK9 как альтернатива при непереносимости статинов. Безопасность и риск фармакотерапии. 2023. Т. 11, № 4. С. 442–449. EDN: OZZYFX doi: 10.30895/2312-7821-2023-366

[31] Vatutin NT, Taradin GG, Rakitskaya IV, et al. Hypolipidemic therapy in insufficient efficacy or intolerance of statins (literature review). Bulletin of Emergency and Restorative Therapy. 2020;5(4):29–39. EDN: VPAHIT

[32] Ватутин Н.Т., Тарадин Г.Г., Ракитская И.В., и др. Гиполипидемическая терапия при недостаточной эффективности или непереносимости статинов (обзор литературы) // Вестник неотложной и восстановительной терапии. 2020. Т. 5, № 4. С. 29–39. EDN: VPAHIT

[33] O’Donoghue ML, Giugliano RP, Wiviott SD, et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation. 2022;146(15):1109–1119. doi: 10.1161/CIRCULATIONAHA.122.061620

[34] O’Donoghue M.L., Giugliano R.P., Wiviott S.D., et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease // Circulation. 2022. Vol. 146, N 15. P. 1109–1119. doi: 10.1161/CIRCULATIONAHA.122.061620

[35] Santos RD, Ruzza A, Hovingh GK, et al. Paediatric patients with heterozygous familial hypercholesterolaemia treated with evolocumab for 80 weeks (HAUSER-OLE): a single-arm, multicentre, open-label extension of HAUSER-RCT. Lancet Diabetes Endocrinol. 2022;10(10):732–740. doi: 10.1016/S2213-8587(22)00221-2

[36] Santos R.D., Ruzza A., Hovingh G.K., et al. Paediatric patients with heterozygous familial hypercholesterolaemia treated with evolocumab for 80 weeks (HAUSER-OLE): a single-arm, multicentre, open-label extension of HAUSER-RCT // Lancet Diabetes Endocrinol. 2022. Vol. 10, N 10. P. 732–740. doi: 10.1016/S2213-8587(22)00221-2

[37] Ezhov MV, Kukharchuk VV. Disorders of lipid metabolism. Clinical guidelines 2023. Russian Cardiology Journal. 2023;28(5):54–71. EDN: YVZOWJ doi: 10.15829/1560-4071-2023-5471

[38] Ежов М.В., Кухарчук В.В. Нарушения липидного обмена. Клинические рекомендации 2023 // Российский кардиологический журнал 2023. Т. 28, № 5. С. 54–71. EDN: YVZOWJ doi: 10.15829/1560-4071-2023-5471

[39] Voyevoda MI, Gurevich VS, Ezhov MV, et al. Inclisiran — a new era in lipid-lowering therapy. Cardiology. 2022;62(6):57–62. EDN: NEWLUX doi: 10.18087/cardio.2022.6.n2115

[40] Воевода М.И., Гуревич В.С., Ежов М.В., и др. Инклисиран — новая эра в гиполипидемической терапии // Кардиология. 2022. Т. 62, № 6. С. 57–62. EDN: NEWLUX doi: 10.18087/cardio.2022.6.n2115

[41] Jain P. Traditional and novel non-statin lipid-lowering drugs. Indian Heart J. 2024;76(Suppl 1):S38–S43. doi: 10.1016/j.ihj.2023.11.003

[42] Jain P. Traditional and novel non-statin lipid-lowering drugs // Indian Heart J. 2024. Vol. 76, Suppl 1. P. S38–S43. doi: 10.1016/j.ihj.2023.11.003

[43] Petrosyan AS, Rud RS, Polyakov PP, et al. The pathogenetic basis of the action of bempedoic acid. Rational Pharmacotherapy in Cardiology. 2022;18(6):734–741. EDN: HLENQU doi: 10.20996/1819-6446-2022-12

[44] Петросян А.С., Рудь Р.С., Поляков П.П., и др. Патогенетические основы эффектов бемпедоевой кислоты // Рациональная фармакотерапия в кардиологии. 2022. Т. 18, № 6. С. 734–741. EDN: HLENQU doi: 10.20996/1819-6446-2022-12

[45] Tummala R, Gupta M, Devanabanda AR, et al. Bempedoic acid and its role in contemporary management of hyperlipidemia in atherosclerosis. Annals of Medicine. 2022;54(1):1287–1296. EDN: RAOOHE doi: 10.1080/07853890.2022.2059559

[46] Tummala R., Gupta M., Devanabanda A.R., et al. Bempedoic acid and its role in contemporary management of hyperlipidemia in atherosclerosis // Annals of Medicine. 2022. Vol. 54, N 1. P. 1287–1296. EDN: RAOOHE doi: 10.1080/07853890.2022.2059559

[47] Banach M, Duell PB, Gotto AM Jr, et al. Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia. JAMA Cardiol. 2020;5(10):1124–1135. doi: 10.1001/jamacardio.2020.2314

[48] Banach M., Duell P.B., Gotto A.M., et al. Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia // JAMA Cardiol. 2020. Vol. 5, N 10. P. 1124–1135. doi: 10.1001/jamacardio.2020.2314

[49] Ray KK, Bays HE, Catapano AL, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380(11):1022–1032. doi: 10.1056/NEJMoa1803917

[50] Ray K.K., Bays H.E., Catapano A.L., et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol // N Engl J Med. 2019. Vol. 380, N 11. P. 1022–1032. doi: 10.1056/NEJMoa1803917

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