cardioКардиологияKardiologiia0022-90402412-5660Kardiomag10.18087/cardio.n581cardio-709Research ArticleСОВЕТ ЭКСПЕРТОВEXPERT ADVICEВозможности клинического применения препарата эзетимиба Отрио (АО «АКРИХИН», Россия) у пациентов высокого и очень высокого сердечно-сосудистого риска, не достигших целевых значений показателей липидного обмена. Заключение Совета экспертовPossibilities of clinical use of ezetimibe Otrio (JSC “AKRIKHIN”, Russia) in patients with high and very high cardiovascular risk who have not reached the target values of lipid metabolism. Conclusion of the Board of expertsКобалаваЖ. Д.KobalavaJ. D.

117198, Russia, Moscow, ul. Miklukho-Maklaya, 6, 

ГуревичВ. С.GurevichV. S.

Clinical-research center “Cardiology”, Department of Atherosclerosis of SPbU

199034, Russia, St Petersburg, Universitetskaya Emb., 11; 195067, Russia, St. Petersburg, Piskarevskij prosp., 47

ГалявичА. С.GalyavichA. M.КаминныйА. И.KaminnyiA. I.КашталапВ. В.KashtalapV. V.МареевВ. Ю.MareevV. Yu.СусековА. В.SusekovA. V.asus99@mail.ruШапошникИ. И.ShaposhnikI. I.

454092, Russia, Chelyabinsk, Vorovskogo str., 64

ФГАОУ ВО «РУДН»РоссияPeople’s Friendship University of RussiaRussian FederationФГБОУ ВО «СПБГУ» МЗ РФ, Научно-клинический центр «Кардиология», отдел атеросклероза; ФГБОУ ВО «СЗГМУ им.И.И. Мечникова» МЗ РФРоссияSaint-Petersburg State University; North-Western State Medical university n.a. I.I. MechnikovRussian FederationФГБОУ ВО «КГМУ» МЗ РФРоссияKazan State Medical UniversityRussian FederationФГБУ НМИЦ Кардиологии, отдел проблем атеросклероза; ФГБОУ ВО «РНИМУ им.Н.И. Пирогова» МЗ РФРоссияNational Medical Research Center of Cardiology, Department of atherosclerosis; Pirogov Russian National Research Medical UniversityRussian FederationФГБНУ «НИИ КПССЗ»; ФГБОУ ВО «КемГМУ» МЗ РФРоссияResearch Institute for Complex Issues of Cardiovascular Diseases; Kemerovo State Medical UniversityRussian FederationМНОЦ МГУ им. М.И. ЛомоносоваРоссияMedical scientific and educational center of Lomonosov Moscow state UniversityRussian FederationФГБОУ ДПО «РМАПО» МЗ РФРоссияAcademy of Postgraduate Medical EducationRussian FederationФГБОУ ВО ЮУГМУРоссияSouth-Ural State Medical UniversityRussian Federation201920062019595S4757Copyright © Kardiomag, 20192019KardiomagKardiomaghttps://cardio.elpub.ru/jour/about/submissions#copyrightNoticehttps://cardio.elpub.ru/jour/article/view/709

Настоящее Заключение Совета экспертов посвящено анализу доказательной базы, месту в современных клинических рекомендациях, анализу эффективности и безопасности, а также возможностям комбинированной терапии статинами и препаратом эзетимиба (Отрио, АО «АКРИХИН») у различных категорий пациентов в повседневной клинической практике в Российской Федерации. Сердечно-сосудистые заболевания (ССЗ) продолжают лидировать в структуре заболеваемости и смертности в РФ. Одним из главных модифицируемых факторов риска ССЗ является гиперхолестеринемия. Основа профилактики и лечения основных осложнений атеросклероза – терапия ингибиторами ГМГ-КоА-редуктазы (статинами), однако достижение целевых уровней ХС ЛНП на фоне монотерапии статинами в российской практике в различных категориях риска не превышает 50%. Часть больных (до 12%) не переносит терапию статинами, что требует поиска альтернативных схем терапии. Для оптимизации контроля уровня холестерина ХС ЛНП применяют комбинированную терапию статинами и  эзетимибом. Эзетимиб  – эффективный гиполипидемический препарат, ингибитор кишечной абсорбции ХС, хорошо изученный в международных и российских исследованиях, результаты которых показали хорошую переносимость, безопасность и эффективность (снижение уровня ХС ЛНП на 18% в монотерапии). Отмечено, что комбинированная терапия низкими/средними дозами статинов и эзетимибом за счет двух синергичных механизмов действия (концепция «двойного ингибирования» ХС) позволяет весьма эффективно снижать уровень ХС ЛНП на 44–53%, что сопоставимо с эффектом высоких доз статинов, а также уменьшает сердечно-сосудистый риск у больных с хронической почечной недостаточностью (ХПН) и ОКС. Препарат Отрио (МНН Эзетимиб), таблетки 10 мг (АО «АКРИХИН», Россия) биоэквивалентен оригинальному препарату Эзетрол®, таблетки 10 мг (Шеринг-Плау Лабо Н В, Бельгия). Широкое применение генерического препарата Отрио в комбинации с различными статинами позволит значительно увеличить частоту достижения целевых уровней липидов у больных высокого и очень высокого сердечно-сосудистого риска, в том числе у пациентов с ХПН, СД 2 типа и у лиц с высокой гиперхолестеринемией (ХС ЛНП >5 ммоль/л) и, в тем самым, уменьшить бремя сердечно-сосудистых заболеваний и смертности в РФ. 

This Conclusion of the Board of experts is devoted to the analysis of the evidence base, the position in modern clinical guidelines, the efficacy and safety analysis as well as the options of combined therapy with statins and ezetimibe (Otrio, JSC “AKRIKHIN”) in various categories of patients in routine clinical practice in theRussian Federation. Cardiovascular diseases (CVD) continue to lead in the structure of morbidity and mortality inRussia. Hypercholesterolemia is one of the main modifiable risk factors for CVD. Administration of HMGCo-A-reductase inhibitors (statins) remains the basis for the prevention and treatment of the main complications of atherosclerosis, but the achievement of target levels of LDL–C on of statin monotherapy in Russian practice among different categories of risk does not exceed 50%. Proportion of patients (up to 12%) does not tolerate statin therapy, which requires the search for alternative therapies. To optimize the control of the level of LDL–C, combination therapy with statins and ezetimibe is used. Ezetimibe is an effective lipid-lowering drug, an inhibitor of intestinal absorption of cholesterol, which was investigated in many international and Russian studies, the results of which have demonstrated good tolerability, safety and efficacy (reduction of LDL–C levels by 18% in monotherapy). It was noted that the combined therapy with low/medium doses of statins and ezetimibe effectively reduces the level of LDL–C by 44–53%, which is comparable to the effect of high doses of statins and reduces CV risk in patients with CKD and ACS. Otrio (INN Ezetimib) tablets 10 mg ( JSC “AKRIKHIN”,Russia) has demonstrated bioequivalence to the original drug Ezetrol tablets 10 mg (Schering-plough Labo N. V,Belgium). Broad use of a new generic product Otrio in combination with different statins will significantly increase the frequency of achievement of target lipid levels in patients with high and very high CV risk, including patients with chronic renal failure, type 2 diabetes and in patients with high hypercholesterolemia (LDL–C > 5 mmol/l) and, ultimately, reduce the burden of CV disease and mortality in Russia. 

гиперлипидемиягиперхолестеринемияингибиторы ГМГ-КоА-редуктазыстатиныингибитор кишечной абсорбции холестеринаэзетимибОтриокомбинированная терапияhyperlipidemiahypercholesterolemiaHMG-COA reductase inhibitorsstatinscholesterol intestinal absorption inhibitorsezetimibeOtriocombination therapyReferencesБойцов С.А., Шальнова С.А., Деев А.Д. Смертность от сердечно-сосудистых заболеваний в Российской Федерации и возможные механизмы ее изменения. Журнал неврологии и психиатрии им.С.С. Корсакова. 2018;118(8):98-103. DOI: 10.17116/jnevro201811808198Boytsov S.A., Shalnova S.A., Deev A. D. Cardiovascular mortality in the Russian Federation and possible mechanisms of its changes. S. S. Korsakov Journal of Neurology and Psychiatry. 2018;118 (8):98–103. [Rusian]. DOI: 10.17116/jnevro201811808198Russian: Шальнова С.А., Деев А.Д., Баланова Ю.А., Капустина А.В., Имаева А.Э., Муромцева Г.А. и др. Двадцатилетние тренды ожирения и артериальной гипертонии и их ассоциации в России. Кардиоваскулярная терапия и профилактика. 2017;16(4):4-10. DOI: 10.15829/1728-8800-2017-4-4-10Shal’nova S. A., Deev A. D., Balanova Yu.A., Kapustina A.V., Imaeva A. E., Muromtseva G.A. et al. Twenty years trends of obesity and arterial hypertension and their association in Russia. Cardiovascular Therapy and Prevention. 2017;16 (4):4–10. [Russian]. DOI: 10.15829/1728-8800-2017-4-4-10Муромцева Г.А., Концевая А.В., Константинов В.В., Артамонова Г.В., Гатагонова Т.М., Дупляков Д.В. и др. Распространенность факторов риска неинфекционных заболеваний в российской популяции в 2012-2013гг. Результаты исследования ЭССЕ-РФ. Кардиоваскулярная терапия и профилактика. 2014;13(6):4-11Muromtceva G. A., Kontsevaya A.V., Konstantinov V.V., Artamonova G.V., Gatagonova T.M., Duplyakov D.V. et al. The prevalence of non-infectious disease risk factors in the Russian population in 2012–2013. Results of the ESSE-RF study. Кардиоваскулярная терапия и профилактика. 2014;13 (6):4–11. [Russian]Ахмеджанов Н. М., Небиеридзе Д.В., Сафарян А.С., Выгодин В.А., Шураев А.Ю., Ткачева О.Н. и др. Анализ распространенности гиперхолестеринемии в условиях амбулаторной практики (по данным исследования АРГО): часть I. Рациональная фармакотерапия в кардиологии. 2015;11(3):253-60Akhmedzhanov N. M., Nebieridze D.V., Safaryan A. S., Vygodin V.A., Shuraev A. Yu., Tkacheva O.N. et al. Analysis of hypercholesterolemia prevalence in the outpatient practice (according to the ARGO study): part I. Rational Pharmacotherapy in Cardiology. 2015;11 (3):253–60. [Russian]Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal. 2017;38(32):2459–72. DOI: 10.1093/eurheartj/ehx144Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal. 2017;38(32):2459–72. DOI: 10.1093/eurheartj/ehx144Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. European Heart Journal. 2016;37(39):2999– 3058. DOI: 10.1093/eurheartj/ehw272Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. European Heart Journal. 2016;37(39):2999– 3058. DOI: 10.1093/eurheartj/ehw272Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS 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. Circulation. 2018; [Epub ahead of print]. DOI: 10.1161/CIR.0000000000000625Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS 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. Circulation. 2018; [Epub ahead of print]. DOI: 10.1161/CIR.0000000000000625Blazing MA, Giugliano RP, de Lemos JA, Cannon CP, Tonkin A, Ballantyne CM et al. On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). American Heart Journal. 2016;182:89–96. DOI: 10.1016/j.ahj.2016.09.004Blazing MA, Giugliano RP, de Lemos JA, Cannon CP, Tonkin A, Ballantyne CM et al. On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). American Heart Journal. 2016;182:89–96. DOI: 10.1016/j.ahj.2016.09.004Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine. 2017;376(18):1713–22. DOI: 10.1056/NEJMoa1615664Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine. 2017;376(18):1713–22. DOI: 10.1056/NEJMoa1615664Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine. 2017;377(12):1119–31. DOI: 10.1056/NEJMoa1707914Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. New England Journal of Medicine. 2017;377(12):1119–31. DOI: 10.1056/NEJMoa1707914Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. New England Journal of Medicine. 2018;379(22):2097–107. DOI: 10.1056/NEJMoa1801174Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. New England Journal of Medicine. 2018;379(22):2097–107. DOI: 10.1056/NEJMoa1801174Ray KK, Stoekenbroek RM, Kallend D, Leiter LA, Landmesser U, Wright RS et al. Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins: Prespecified Secondary End Points in ORION 1. Circulation. 2018;138(13):1304–16. DOI: 10.1161/CIRCULATIONAHA.118.034710Ray KK, Stoekenbroek RM, Kallend D, Leiter LA, Landmesser U, Wright RS et al. Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins: Prespecified Secondary End Points in ORION 1. Circulation. 2018;138(13):1304–16. DOI: 10.1161/CIRCULATIONAHA.118.034710Ballantyne CM, McKenney JM, MacDougall DE, Margulies JR, Robinson PL, Hanselman JC et al. Effect of ETC-1002 on Serum LowDensity Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy. The American Journal of Cardiology. 2016;117(12):1928–33. DOI: 10.1016/j.amjcard.2016.03.043Ballantyne CM, McKenney JM, MacDougall DE, Margulies JR, Robinson PL, Hanselman JC et al. Effect of ETC-1002 on Serum LowDensity Lipoprotein Cholesterol in Hypercholesterolemic Patients Receiving Statin Therapy. The American Journal of Cardiology. 2016;117(12):1928–33. DOI: 10.1016/j.amjcard.2016.03.043Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al. 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) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). European Heart Journal. 2016;37(29):2315–81. DOI: 10.1093/eurheartj/ehw106Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al. 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) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). European Heart Journal. 2016;37(29):2315–81. DOI: 10.1093/eurheartj/ehw106Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. The Lancet. 2005;366(9493):1267–78. DOI: 10.1016/S0140-6736(05)67394-1Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. The Lancet. 2005;366(9493):1267–78. DOI: 10.1016/S0140-6736(05)67394-1Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a metaanalysis of data from 170 000 participants in 26 randomised trials. The Lancet. 2010;376(9753):1670–81. DOI: 10.1016/S0140-6736(10)61350-5Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a metaanalysis of data from 170 000 participants in 26 randomised trials. The Lancet. 2010;376(9753):1670–81. DOI: 10.1016/S0140-6736(10)61350-5Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The Lancet. 2012;380(9841):581– 90. DOI: 10.1016/S0140-6736(12)60367-5Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The Lancet. 2012;380(9841):581– 90. DOI: 10.1016/S0140-6736(12)60367-5Fulcher J, O’Connell R, Voysey M, Emberson J, Blackwell L, Mihaylova B et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174 000 participants in 27 randomised trials. The Lancet. 2015;385(9976):1397–405. DOI: 10.1016/S01406736(14)61368-4Fulcher J, O’Connell R, Voysey M, Emberson J, Blackwell L, Mihaylova B et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174 000 participants in 27 randomised trials. The Lancet. 2015;385(9976):1397–405. DOI: 10.1016/S01406736(14)61368-4Mach F, Ray KK, Wiklund O, Corsini A, Catapano AL, Bruckert E et al. Adverse effects of statin therapy: perception vs. the evidence – focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. European Heart Journal. 2018;39(27):2526–39. DOI: 10.1093/eurheartj/ehy182Mach F, Ray KK, Wiklund O, Corsini A, Catapano AL, Bruckert E et al. Adverse effects of statin therapy: perception vs. the evidence – focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. European Heart Journal. 2018;39(27):2526–39. DOI: 10.1093/eurheartj/ehy182Endo A. The discovery and development of HMG-CoA reductase inhibitors. Journal of Lipid Research. 1992;33(11):1569– 82. PMID: 1464741Endo A. The discovery and development of HMG-CoA reductase inhibitors. Journal of Lipid Research. 1992;33(11):1569– 82. PMID: 1464741Turley SD. Dietary cholesterol and mechanisms of cholesterol absorption. European Heart Journal. 1999;1(Suppl):S29–35Turley SD. Dietary cholesterol and mechanisms of cholesterol absorption. European Heart Journal. 1999;1(Suppl):S29–35Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. European Heart Journal. 2015;36(17):1012–22. DOI: 10.1093/eurheartj/ehv043Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. European Heart Journal. 2015;36(17):1012–22. DOI: 10.1093/eurheartj/ehv043Stein EA, Ballantyne CM, Windler E, Sirnes PA, Sussekov A, Yigit Z et al. Efficacy and Tolerability of Fluvastatin XL 80 mg Alone, Ezetimibe Alone, and the Combination of Fluvastatin XL 80 mg With Ezetimibe in Patients With a History of MuscleRelated Side Effects With Other Statins. The American Jour nal of Cardiology. 2008;101(4):490–6. DOI: 10.1016/j.amjcard.2007.09.099Stein EA, Ballantyne CM, Windler E, Sirnes PA, Sussekov A, Yigit Z et al. Efficacy and Tolerability of Fluvastatin XL 80 mg Alone, Ezetimibe Alone, and the Combination of Fluvastatin XL 80 mg With Ezetimibe in Patients With a History of MuscleRelated Side Effects With Other Statins. The American Jour nal of Cardiology. 2008;101(4):490–6. DOI: 10.1016/j.amjcard.2007.09.099Оганов Р. Г., Кухарчук В. В., Арутюнов Г.П., Галявич А.С., Гуревич В.С., Дупляков Д. В. и др. Сохраняющиеся нарушения показателей липидного спектра у пациентов с дислипидемией, по лучающих статины, в реальной клинической практике в Российской Федерации (российская часть исследования DYSIS). Кардиоваскулярная терапия и профилактика. 2012;11(4):70-8Oganov R.G., Kukharchuk V.V., Arutyunov G.P., Galyavich A.S., Gurevich V. S., Duplyakov D.V. et al. Persistent dyslipidemia in statin-treated patients: Russian real-world clinical practice data (Russian part of the DYSIS Study). Cardiovascular Therapy and Prevention. 2012;11 (4):70–8. [Russian]Ершова А.И., Мешков А.Н., Якушин С.С., Лукьянов М.М., Мосейчук К.А., Марцевич С.Ю. и др. Диагностика и лечение больных с выраженной гиперхолестеринемией в реальной амбулаторно-клинической практике. (по данным регистра РЕКВАЗА). Рациональная фармакотерапия в кардиологии. 2014;10(6):612-6Ershova A.I., Meshkov A.N., Yakushin S.S., Loukianov M.M., Moseychuk K.A., Martsevich S.Yu. et al. Diagnosis and treatment of patients with severe hypercholesterolemia in real outpatient practice (according to the RECVASA registry). Rational Pharmacotherapy in Cardiology. 2014;10(6):612–6. [Russian]Gitt AK, Lautsch D, Ferrières J, De Ferrari GM, Vyas A, Baxter CA et al. Contemporary data on treatment practices for low-density lipoprotein cholesterol in 6794 patients with stable coronary heart disease across the world. Data in Brief. 2018;18:1937–40. DOI: 10.1016/j.dib.2018.04.092Gitt AK, Lautsch D, Ferrières J, De Ferrari GM, Vyas A, Baxter CA et al. Contemporary data on treatment practices for low-density lipoprotein cholesterol in 6794 patients with stable coronary heart disease across the world. Data in Brief. 2018;18:1937–40. DOI: 10.1016/j.dib.2018.04.092Rosenblum SB, Huynh T, Afonso A, Davis HR, Yumibe N, Clader JW et al. Discovery of 1-(4-Fluorophenyl)-(3 R)-[3-(4fluorophenyl)-(3 S)hydroxypropyl]-(4 S)-(4-hydroxyphenyl)2-azetidinone (SCH 58235): A Designed, Potent, Orally Active Inhibitor of Cholesterol Absorption. Journal of Medicinal Chemistry. 1998;41(6):973–80. DOI: 10.1021/jm970701fRosenblum SB, Huynh T, Afonso A, Davis HR, Yumibe N, Clader JW et al. Discovery of 1-(4-Fluorophenyl)-(3 R)-[3-(4fluorophenyl)-(3 S)hydroxypropyl]-(4 S)-(4-hydroxyphenyl)2-azetidinone (SCH 58235): A Designed, Potent, Orally Active Inhibitor of Cholesterol Absorption. Journal of Medicinal Chemistry. 1998;41(6):973–80. DOI: 10.1021/jm970701fSparrow CP, Patel S, Baffic J, Chao YS, Hernandez M, Lam MH et al. A fluorescent cholesterol analog traces cholesterol absorption in hamsters and is esterified in vivo and in vitro. Journal of Lipid Research. 1999;40(10):1747–57. PMID: 10508194Sparrow CP, Patel S, Baffic J, Chao YS, Hernandez M, Lam MH et al. A fluorescent cholesterol analog traces cholesterol absorption in hamsters and is esterified in vivo and in vitro. Journal of Lipid Research. 1999;40(10):1747–57. PMID: 10508194Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Toth PD, Dujovne CA et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clinical Therapeutics. 2001;23(8):1209– 30. PMID: 11558859Bays HE, Moore PB, Drehobl MA, Rosenblatt S, Toth PD, Dujovne CA et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clinical Therapeutics. 2001;23(8):1209– 30. PMID: 11558859Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. Journal of the American College of Cardiology. 2002;40(12):2125–34. PMID: 12505224Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. Journal of the American College of Cardiology. 2002;40(12):2125–34. PMID: 12505224Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R et al. Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia: A Prospective, Randomized, Double-Blind Trial. Circulation. 2003;107(19):2409– 15. DOI: 10.1161/01.CIR.0000068312.21969.C8Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R et al. Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia: A Prospective, Randomized, Double-Blind Trial. Circulation. 2003;107(19):2409– 15. DOI: 10.1161/01.CIR.0000068312.21969.C8Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F et al. Efficacy and Safety of Rosuvastatin 40 mg Alone or in Combination With Ezetimibe in Patients at High Risk of Cardiovascular Disease (Results from the EXPLORER Study). The American Journal of Cardiology. 2007;99(5):673–80. DOI: 10.1016/j.amjcard.2006.10.022Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F et al. Efficacy and Safety of Rosuvastatin 40 mg Alone or in Combination With Ezetimibe in Patients at High Risk of Cardiovascular Disease (Results from the EXPLORER Study). The American Journal of Cardiology. 2007;99(5):673–80. DOI: 10.1016/j.amjcard.2006.10.022Gagné C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. The American Journal of Cardiology. 2002;90(10):1084–91. PMID: 12423708Gagné C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. The American Journal of Cardiology. 2002;90(10):1084–91. PMID: 12423708Catapano AL, Davidson MH, Ballantyne CM, Brady WE, Gazzara RA, Tomassini JE et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Current Medical Research and Opinion. 2006;22(10):2041–53. DOI: 10.1185/030079906X132721Catapano AL, Davidson MH, Ballantyne CM, Brady WE, Gazzara RA, Tomassini JE et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Current Medical Research and Opinion. 2006;22(10):2041–53. DOI: 10.1185/030079906X132721Catapano A, Brady WE, King TR, Palmisano J. Lipid alteringefficacy of ezetimibe co-administered with simvastatin compared with rosuvastatin: a meta-analysis of pooled data from 14 clinical trials. Current Medical Research and Opinion. 2005;21(7):1123–30. DOI: 10.1185/030079905X50642Catapano A, Brady WE, King TR, Palmisano J. Lipid alteringefficacy of ezetimibe co-administered with simvastatin compared with rosuvastatin: a meta-analysis of pooled data from 14 clinical trials. Current Medical Research and Opinion. 2005;21(7):1123–30. DOI: 10.1185/030079905X50642Kastelein JJP, Akdim F, Stroes ESG, Zwinderman AH, Bots ML, Stalenhoef AFH et al. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia. New England Journal of Medicine. 2008;358(14):1431–43. DOI: 10.1056/NEJMoa0800742Kastelein JJP, Akdim F, Stroes ESG, Zwinderman AH, Bots ML, Stalenhoef AFH et al. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia. New England Journal of Medicine. 2008;358(14):1431–43. DOI: 10.1056/NEJMoa0800742Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. New England Journal of Medicine. 2008;359(13):1343–56. DOI: 10.1056/NEJMoa0804602Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. New England Journal of Medicine. 2008;359(13):1343–56. DOI: 10.1056/NEJMoa0804602Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. The Lancet. 2011;377(9784):2181–92. DOI: 10.1016/S0140-6736(11)60739-3Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. The Lancet. 2011;377(9784):2181–92. DOI: 10.1016/S0140-6736(11)60739-3Fleg JL, Mete M, Howard BV, Umans JG, Roman MJ, Ratner RE et al. Effect of Statins Alone Versus Statins Plus Ezetimibe on Carotid Atherosclerosis in Type 2 Diabetes. Journal of the American College of Cardiology. 2008;52(25):2198–205. DOI: 10.1016/j.jacc.2008.10.031Fleg JL, Mete M, Howard BV, Umans JG, Roman MJ, Ratner RE et al. Effect of Statins Alone Versus Statins Plus Ezetimibe on Carotid Atherosclerosis in Type 2 Diabetes. Journal of the American College of Cardiology. 2008;52(25):2198–205. DOI: 10.1016/j.jacc.2008.10.031Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. New England Journal of Medicine. 2015;372(25):2387–97. DOI: 10.1056/NEJMoa1410489Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. New England Journal of Medicine. 2015;372(25):2387–97. DOI: 10.1056/NEJMoa1410489Ference BA, Majeed F, Penumetcha R, Flack JM, Brook RD. Effect of Naturally Random Allocation to Lower Low-Density Lipoprotein Cholesterol on the Risk of Coronary Heart Disease Mediated by Polymorphisms in NPC1L1, HMGCR, or Both. Journal of the American College of Cardiology. 2015;65(15):1552–61. DOI: 10.1016/j.jacc.2015.02.020Ference BA, Majeed F, Penumetcha R, Flack JM, Brook RD. Effect of Naturally Random Allocation to Lower Low-Density Lipoprotein Cholesterol on the Risk of Coronary Heart Disease Mediated by Polymorphisms in NPC1L1, HMGCR, or Both. Journal of the American College of Cardiology. 2015;65(15):1552–61. DOI: 10.1016/j.jacc.2015.02.020Сусеков А.В., Зубарева М.Ю., Кухарчук В.В. Результаты наблюдательной программы по эзетролу «Исследование двух столиц». Фарматека. 2006;8:65-70Susekov A.V., Zubareva M.Yu., Kukharchuk V.V. Results of the observation program on ezetrol “Study of two capitals“. Pharmateka. 2006;8:65–70. [Russian]Зубарева М.Ю., Рожкова Т.А., Соловьева Е.Ю., Сусеков А.В. Рандомизированное исследование ЭСКАДРА. Часть 1: гиполипидемическая эффективность, безопасность и переносимость эзетимиба, начальных доз оригинальных статинов и комбинации эзетимиба с начальными дозами статинов у больных ишемической болезнью сердца и гиперлипопротеидемией. Кардиоваскулярная терапия и профилактика. 2010;9(6):74-82Zubareva M.Yu., Rozhkova Т.А., Solovyeva E.Yu., Susekov A.V. ESCADRA: a randomised study. Part I: lipid-lowering effectiveness, safety and tolerability of ezetimibe, initial doses of original statins, and the combination of ezetimibe with initial doses of statins in patients with coronary heart disease and hyperlipidemia. Cardiovascular Therapy and Prevention. 2010;9(6):74– 82. [Russian]Landmesser U, John Chapman M, Farnier M, Gencer B, Gielen S, Hovingh GK et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. European Heart Journal. 2017;38(29):2245–55. DOI: 10.1093/eurheartj/ehw480Landmesser U, John Chapman M, Farnier M, Gencer B, Gielen S, Hovingh GK et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. European Heart Journal. 2017;38(29):2245–55. DOI: 10.1093/eurheartj/ehw480Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society. European Heart Journal. 2013;34(45):3478–90. DOI: 10.1093/eurheartj/eht273Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society. European Heart Journal. 2013;34(45):3478–90. DOI: 10.1093/eurheartj/eht273Бойцов С.А., Погосова Н.В., Бубнова М.Г., Драпкина О.М., Гаврилова Н.Е., Еганян Р.А. и др. Кардиоваскулярная профилактика 2017. Российские национальные рекомендации. Российский кардиологический журнал. 2018;23(6):7–122. DOI: 10.15829/1560-4071-20186-7-122Boytsov S.A., Pogosova N.V., Bubnova M.G., Drapkina O.M., Gavrilova N.E., Yeganyan R.A. et al. Cardiovascular prevention 2017. National guidelines. Russian Journal of Cardiology. 2018;23(6):7–122. [Russian]. DOI: 10.15829/1560-4071-20186-7-122Толкачева В.В., Малая И.П., Багманова Н.Х., Кобалава Ж.Д. Изучение биоэквивалентности препаратов эзетимиба у здоровых добровольцев после однократного приема натощак. Consilium Medicum. 2019;21(1):87–91. DOI: 10.26442/20751753.2019.1.190205Tolkacheva V.V., Malaya I.P., Bagmanova N.Kh., Kobalava Zh.D. Study of bioequivalence of ezetimibe drugs in healthy volunteers after a single fasting. Consilium Medicum. 2019;21(1):87– 91. [Russian]. DOI: 10.26442/20751753.2019.1.190205Аронов Д.М., Арабидзе Г.Г., Ахмеджанов Н.М., Балахонова Т.В., Бойцов С.А., Бубнова М.Г. и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации. VI пересмотр. 2017;1-44. Доступно на: https://noatero.ru/sites/default/files/references_v6.pdfAronov D.M., Arabidze G.G., Akhmedzhanov N.M., Balakhonova T.V., Barbarash O.L., Boytsov S.A. et al. Diagnostics and correction of lipid metabolism disorders for the prevention and treatment of atherosclerosis. Russian recommendations. VI revision. 2017;1–44. [Russian https://noatero.ru/sites/default/files/references_v6.pdf

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