Achieving target lipid levels with statin and ezetimibe combination therapy

Cover Page

Cite item

Full Text

Abstract

The article discusses the issues of achieving target lipid values when using different lipid-lowering therapy regimens. The use of a combination of low/medium doses of statins and ezetimibe acts through complementary mechanisms: a decrease in intracellular cholesterol concentration with increased capture of LDL-C by hepatocytes (statins) and a decrease in cholesterol absorption in the intestine (ezetimibe). This allows you to achieve a reduction in LDL cholesterol by 45-65%. In addition, combination therapy with statin and ezetimibe is safe and cost-effective. The combination of statin and ezetimibe makes it possible to more effectively achieve target lipid values in comparison with statin monotherapy. Thus, among patients taking a combination therapy, the achievement of target values of LDL cholesterol is observed in more than 70% of cases. The addition of ezetimibe to a statin is associated with an increase in the probability of reaching target LDL values 2.5-3.2 times. In accordance with current international recommendations, the prescription of ezetimibe is possible both in monotherapy mode (with statin intolerance) and as part of combination therapy. In the framework of combined lipid-lowering therapy, the administration of ezetimibe is recommended in addition to the statin (“on top”) in case of failure to achieve the target lipid values. Adding ezetimibe at a dose of 10 mg/day to statin therapy can be recommended in most patients at high and very high risk if target levels of LDL cholesterol are not achieved within 4-12 weeks after starting therapy. Generic product of ezetimibe - Otrio, tablets 10 mg (JSC “Akrikhin”, Russia) is bioequivalent to the original drug Ezetrol® 10 mg (“Schering-plough Labo N.V.”, Belgium). Usage of Otrio in combination with different statins will make combination therapy of hypercholesterolemia more accessible and will increase the frequency of achievement of target levels of lipids in patients with high and very high CV risk (including familial hypercholesterolemia, CRD and diabetes).

About the authors

Igor I. Shaposhnik

South-Ural State Medical University

Email: shaposhnik@yandex.ru
D. Sci. (Med.), Prof. Chelyabinsk, Russia

Vadim V. Genkel

South-Ural State Medical University

Email: henkel-07@mail.ru
Cand. Sci. (Med.) Chelyabinsk, Russia

References

  1. Ежов М.В., Близнюк С.А., Алексеева И.А., Выгодин В.А. Распространенность гиперхолестеринемии и применения статинов в амбулаторной практике в Российской Федерации. Исследование Айсберг - диагностирование пациентов с гиперхолестеринемией в условиях амбулаторной практики на раннем этапе с целью улучшения сердечно-сосудистого прогноза. Атеросклероз и дислипидемии. 2017; 4 (29): 5-17.@@Ezhov M.V., Blizniuk S.A., Alekseeva I.A., Vygodin V.A. Rasprostranennost' giperkholesterinemii i primeneniia statinov v ambulatornoi praktike v Rossiiskoi Federatsii. Issledovanie Aisberg - diagnostirovanie patsientov s giperkholesterinemiei v usloviiakh ambulatornoi praktiki na rannem etape s tsel'iu uluchsheniia serdechno-sosudistogo prognoza. Ateroskleroz i dislipidemii. 2017; 4 (29): 5-17
  2. Мешков А.Н., Ершова А.И., Деев А.Д. и др. Распределение показателей липидного спектра у мужчин и женщин трудоспособного возраста в Российской Федерации: результаты исследования ЭССЕ-РФ за 2012-2014 гг. Кардиоваскулярная терапия и профилактика. 2017; 16 (4): 62-7. @@Meshkov A.N., Ershova A.I., Deev A.D. et al. Raspredelenie pokazatelei lipidnogo spektra u muzhchin i zhenshchin trudosposobnogo vozrasta v Rossiiskoi Federatsii: rezul'taty issledovaniia ESSE-RF za 2012-2014 gg. Kardiovaskuliarnaia terapiia i profilaktika. 2017; 16 (4): 62-7
  3. Концевая А.В., Баланова Ю.А., Имаева А.Э. и др. Экономический ущерб от гиперхолестеринемии на популяционном уровне в Российской Федерации. Рациональная фармакотерапия в кардиологии. 2018; 14 (3): 393-401. @@Kontsevaia A.V., Balanova Iu.A., Imaeva A.E. et al. Ekonomicheskii ushcherb ot giperkholesterinemii na populiatsionnom urovne v Rossiiskoi Federatsii. Ratsional'naia farmakoterapiia v kardiologii. 2018; 14 (3): 393-401
  4. Kotseva K, De Backer G, De Bacquer D et al. Lifestyle and impact on cardiovascular risk factor control in coronary patients across 27 countries: Results from the European Society of Cardiology ESC-EORP EUROASPIRE V registry. Eur J Prev Cardiol 2019. doi: 10.1177/2047487318825350
  5. Takase H, Dohi Y, Okado T et al. Effects of ezetimibe on visceral fat in the metabolic syndrome: a randomised controlled study. Eur J Clin Invest 2012; 42 (12): 1287-94. doi: 10.1111/eci.12000
  6. Koh K.K, Oh P.C, Sakuma I et al. Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia. Int J Cardiol 2015; 199: 126-31. doi: 10.1016/j.ijcard.2015.07.016.
  7. Ohbu-Murayama K, Adachi H, Hirai Y et al. Ezetimibe combined with standard diet and exercise therapy improves insulin resistance and atherosclerotic markers in patients with metabolic syndrome. J Diabetes Investig 2015; 6 (3): 325-33. doi: 10.1111/jdi.12298
  8. Wu H, Shang H, Wu J. Effect of ezetimibe on glycemic control: a systematic review and meta-analysis of randomized controlled trials. Endocrine 2018; 60 (2): 229-39. doi: 10.1007/s12020-018-1541-4
  9. Nakade Y, Murotani K, Inoue T, Kobayashi Y et al. Ezetimibe for the treatment of non-alcoholic fatty liver disease: A meta-analysis. Hepatol Res 2017; 47 (13): 1417-28. doi: 10.1111/hepr.12887
  10. Kalogirou M, Tsimihodimos V, Elisaf M. Pleiotropic effects of ezetimibe: do they really exist? Eur J Pharmacol 2010; 633 (1-3): 62-70. doi: 10.1016/j.ejphar.2010.02.003
  11. Hong N, Lee Y.H, Tsujita K et al. Comparison of the Effects of Ezetimibe-Statin Combination Therapy on Major Adverse Cardiovascular Events in Patients with and without Diabetes: A Meta-Analysis. Endocrinol Metab (Seoul) 2018; 33 (2): 219-27. doi: 10.3803/EnM.2018.33.2.219
  12. Mach F, Ray K.K, Wiklund O et al. Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract. Eur Heart J 2018; 39 (27): 2526-39. doi: 10.1093/eurheartj/ehy182
  13. Catapano A.L, Graham I, De Backer G et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37 (39): 2999-58. doi: 10.1093/eurheartj/ehw272
  14. Ежов М.В., Сергиенко И.В., Аронов Д.М. и др. Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза. Российские рекомендации VI пересмотр. Атеросклероз и дислипидемии. 2017; 3 (28): 5-22. @@Ezhov M.V., Sergienko I.V., Aronov D.M. et al. Diagnostika i korrektsiia narushenii lipidnogo obmena s tsel'iu profilaktiki i lecheniia ateroskleroza. Rossiiskie rekomendatsii VI peresmotr. Ateroskleroz i dislipidemii. 2017; 3 (28): 5-22
  15. Grundy S.M, Stone N.J, Bailey A.L et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation 2018. doi: 10.1161/CIR.0000000000000625
  16. Silverman M.G, Ference B.A, Im K et al. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA 2016; 316 (12): 1289-197. doi: 10.1001/jama.2016.13985
  17. Leibowitz M, Karpati T, Cohen-Stavi C.J et al. Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment. JAMA Intern Med 2016; 176 (8): 1105-13. doi: 10.1001/jamainternmed.2016.2751
  18. Lee J.H, Ko Y.G, Shin D.H et al. Attainment of low-density lipoprotein cholesterol goal after endovascular treatment is associated with reduced cardiovascular events in patients with peripheral arterial disease. J Vasc Surg 2016; 63 (3): 756-63. doi: 10.1016/j.jvs.2015.09.059
  19. Cannon C.P, Blazing M.A, Giugliano R.P et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372: 2387-97. doi: 10.1056/NEJMoa1410489
  20. Giugliano R.P, Pedersen T.R, Park J.G et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet 2017; 390 (10106): 1962-71. doi: 10.1016/S0140-6736(17)32290-0
  21. Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet 2019; 393 (10170): 407-15. doi: 10.1016/S0140-6736(18)31942-1
  22. Ray K.K, Bach R.G, Cannon C.P et al. Benefits of achieving the NCEP optional LDL-C goal among elderly patients with ACS. Eur Heart J 2006; 27 (19): 2310-6. doi: 10.1093/eurheartj/ehl180
  23. Сусеков А.В., Кобалава Ж.Д., Гуревич В.С. и др. Возможности 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 экспертов. Кардиология. 2019; 59 (5S): 47-57.@@Susekov A.V., Kobalava Zh.D., Gurevich V.S. et al. Vozmozhnosti klinicheskogo primeneniia preparata ezetimiba Otrio (AO "AKRIKhIN', Rossiia) u patsientov vysokogo i ochen' vysokogo serdechno-sosudistogo riska, ne dostigshikh tselevykh znachenii pokazatelei lipidnogo obmena. Zakliuchenie Soveta ekspertov. Kardiologiia. 2019; 59 (5S): 47-57.
  24. Kashani A, Sallam T, Bheemreddy S et al. Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials. Am J Cardiol 2008; 101 (11): 1606-13. doi: 10.1016/j.amjcard.2008.01.041
  25. Luo L, Yuan X, Huang W et al. Safety of coadministration of ezetimibe and statins in patients with hypercholesterolaemia: a meta-analysis. Intern Med J 2015; 45 (5): 546-57. doi: 10.1111/imj.12706
  26. Davies G.M, Vyas A, Baxter C.A. Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States. J Med Eco 2017; 20 (7): 723-31. doi: 10.1080/13696998.2017.1320559
  27. Suh D.C, Griggs S.K, Henderson E.R et al. Comparative effectiveness of lipid-lowering treatments to reduce cardiovascular disease. Expert Rev Pharmacoecon Outcomes Res 2018; 18 (1): 51-69. doi: 10.1080/14737167.2018.1407246
  28. Ballantyne C.M, Weiss R, Moccetti T 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). Am J Cardiol 2007; 99: 673-80. doi: 10.1016/j.amjcard.2006.10.022
  29. Gryskiewicz K.A, Coleman C.I, Gillespie E.L et al. Cost-Effectiveness Analysis of Combination Statin/Ezetimibe Therapy for the Treatment of Elevated Low-Density Lipoprotein Cholesterol. Hospital Pharmacy 2005; 40 (8): 687-92. doi: 10.1177/001857870504000808
  30. Wu N.Q, Guo Y.L, Zhu C.G et al. Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers. Lipids Health Dis 2018; 17 (1): 265. doi: 10.1186/s12944-018-0909-z
  31. Foody J.M, Toth P.P, Tomassini J.E et al. Changes in LDL-C levels and goal attainment associated with addition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin compared with titrating statin monotherapy. Vasc Health Risk Manag 2013; 9: 719-27. doi: 10.2147/VHRM.S49840
  32. Ambegaonkar B.M, Tipping D, Polis A.B et al. Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Atherosclerosis 2014; 237 (2): 829-37. doi: 10.1016/j.atherosclerosis.2014.10.105
  33. Lorenzi M, Ambegaonkar B, Baxter C.A et al. Ezetimibe in high-risk, previously treated statin patients: a systematic review and network meta-analysis of lipid efficacy. Clin Res Cardiol 2019; 108 (5): 487-509. doi: 10.1007/s00392-018-1379-z
  34. Landmesser U, Chapman M.J, Farnier M 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. Eur Heart J 2017; 38 (29): 2245-55. doi: 10.1093/eurheartj/ehw480
  35. Lloyd-Jones D.M, Morris P.B, Ballantyne C.M et al. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2017; 70 (14): 1785-822. doi: 10.1016/j.jacc.2017.07.745

Copyright (c) 2019 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies