Features of using of a fixed combination of rosuvastatin and ezetimibe for effective hypolipidemic therapy

Mortality from cardiovascular diseases (CVD) in Russian Federation (RF) remains one of the highest in the world. Compared to 2003, the mortality from CVD decreased by 37%, but when compared with most European countries, it is 3 times higher. Most deaths (53%) occur due to coronary heart disease. While analyzing reasons of mortality, total economic impact due to hypercholesterolemia in RF is estimated as 1,3 trillion RUR annually. The prevalence of hypercholesterolemia is in more than 50% of working-age population in RF. Due to AISBERG study, the prevalence of HCE in ambulatory practice in RF is 84%. When using lipid-lowering medications, the frequency of reaching of target total cholesterol level does not exceed 12%. Active actions on primary and secondary prevention are needed to low mortality rate from CVD, including active promoting of healthy lifestyle, and prescribing if necessary of lipid-lowering therapy (LLT) regimens. The paper deals with significance of target low density lipoprotein cholesterol level in accordance with the latest recommendations as the main aim for LLT. Combined LLT with one of the most potent statins rosuvastatin and ezetimibe seems to be effective and safe strategy for achieving target lipid level in different populations of patients. At present, Rosulip Plus is available in Russia - an quantitative and proven combination of rosuvastatin and ezetimibe.

1. Mach F., Baigent C., Catapano A., Koskinas K., Casula M., Badimon L. et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardio vascular risk: The task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). European Heart Journal. 2020;41(1):111-188. doi: 10.1093/eurheartj/ehz455.

2. Yusuf S., Hawken S., Ounpuu S., Dans T., Avezum A., Lanas F. et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937-952. doi: 10.1016/S0140-6736(04)17018-9.

3. Metelskaya V.A., Shalnova S.A., Deev A.D., Perova N.V., Gomyranova N.V., Litinskaya O.A. et al. Analysis of atherogenic dyslipidemias prevalence among population of Russian Federation (resultsof the ESSE-RF Study). Profilakticheskaya meditsina = Russian Journal of Preventive Medicine and Public Health. 2016;19(1):15-23. (In Russ.) doi: 10.17116/profmed201619115-23.

4. Meshkov A.N., Ershova A.I., Deev A.D., Metelskaya V.A., Zhernakova Yu.V., Rotar O.P. et al. Distribution of lipid profile values in economically active men and women in Russian Federation: results of the ESSE-RF study for the years 2012-2014. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2017;16(4):62-67. (In Russ.) doi: 10.15829/1728-8800-2017-4-62-67.

5. Ezhov M.V., Lazareva N.V., Sagaydak O.V., Vygodin V.A., Chubikina U.V., Blizniuk S.A. et al. Prevalence of Dyslipidemia and Statins Use In Russian Acute Coronary Syndrome Registry. Ateroskleroz i Dislipidemii = The Journal of Atherosclerosis and Dyslipidemias. 2018;1(30):47-57. (In Russ.) Available at: https://noatero.ru/ru/noa/jurnal/2018g-no1-30.

6. Kontsevaya A.V., Balanova Yu.A., Imaeva A.E., Khudyakov M.B., Karpov O.I., Drapkina O.M. Economic burden of hypercholesterolemia in the Russian Federation. Ratsionalnaya farmakoterapiya v kardiologii = Rational Pharmacotherapy in Cardiology. 2018;14(3):393-401. (In Russ.) doi: 10.20996/1819-6446-2018-14-3-393-401.

7. Shalnova SA., Deev A.D., Metelskaya VA., Evstifeeva S.E., Rotar O.P., Zhernakova Yu.V., Boytsov S.A. Awareness and treatment specifics of statin therapy in persons with various cardiovascular risk: the study ESSE-RF. Kardiovasku-lyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2016;15(4):29-37. (In Russ.) doi: 10.15829/1728-8800-2016-4-29-37.

8. Van Dis I. Cardiovascular risk prediction in The Netherlands. Wageningen, The Netherlands: Ipskamp Drukkers B.V.; 2011. 128 p. Available at: https://edepot.wur.nl/186623.

9. Brindle PM., McConnachie A., Upton M.N., Hart C.L., Smith G.D., Watt G.C. The accuracy of the Framingham risk-score in different socioeconomic groups: a prospective study. Br J Gen Pract. 2005;55(520):838-845. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570792.

10. GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. Lancet. 1990;336(8707):65-71. Available at: https://pubmed.ncbi.nlm.nih.gov/1975321.

11. Singh A., Collins B.L., Gupta A., Fatima A., Oamar A., Biery D. et al. Cardiovascular risk and statin eligibility of young adults after an MI: partners YUNG-MI regisrty. J Am Coll Cardiol. 2018;71(3):292-302. doi: 10.1016/j.jacc.2017.11.007.

12. Singh A., Gupta A., Collins B.L., Oamar A., Monda K.L., Biery D. et al. Familial Hypercholesterolemia Among Young Adults With Myocardial Infarction. J Am Coll Cardiol. 2019;73(19):2439-2450. doi: 10.1016/j.jacc.2019.02.059.

13. Ezhov M.V., Bazhan S.S., Ershova A.I., Meshkov A.N., Sokolov A.A., Kukharchuk V.V. et al. Clinical guidelines for familial hypercholesterolemia. Ateroskleroz i Dislipidemii = The Journal of Atherosclerosis and Dyslipidemias. 2019;(1):5-43. (In Russ.) Available at: https://elibrary.ru/item.asp?id=38071474.

14. Ezhov M.V., Blizniuk S.A., Alekseeva I.A., Vygodin V.A. Prevalence of hypercholesterolemia and statins intake in the outpatient practice in the Russian Federation (Iceberg study). Ateroskleroz i Dislipidemii = The Journal of Atherosclerosis and Dyslipidemias. 2017;(4):5-17. (In Russ.) Available at: https://elibrary.ru/item.asp?id=34905607.

15. Brown M.T., Bussell J.K. Medication adherence: WHO cares? Mayo Clin Proc. 2011;86(4):304-314. doi: 10.4065/mcp.2010.0575.

16. Vartiainen E., Laatikainen T., Peltonen M., Juolevi A., Mannisto S.,Sundvall J. et al. Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol. 2010;39(2):504-518. doi: 10.1093/ije/dyp330.

17. Diagnostics and correction of lipid metabolism disorders in order to prevent and treat of atherosclerosis Russian recommendations VII revision. Moscow, 2020. Ateroskleroz i Dislipidemii = The Journal of Atherosclerosis and Dyslipidemias. 2020;(1):7-40. (In Russ.) doi: 10.34687/2219-8202.JAD.2020.01.0002.

18. Baigent C., Blackwell L., Emberson J., Holland L.E., Reith C., Bhala N. et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a metaanalysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. doi: 10.1016/S0140-6736(10)61350-5.

19. Kotseva K., Wood D., De Bacquer D., De Backer G., Ryden L., Jennings C. et al. EUROASPIRE IV: a European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur J Prev Cardiol. 2016;23(6):636-648. doi: 10.1177/2047487315569401.

20. De Backer G., Jankowski P., Kotseva K., Mirrakhimov E., Reiner Z., Ryden L. et al. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis. 2019;285:135-146. doi: 10.1016/j.atherosclero-sis.2019.03.014.

21. Catapano A.L., Graham I., De Backer G., Wiklund O., Chapman MJ., Drexel H. et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016;37(39):2999-3058. doi: 10.1093/eurheartj/ehw272.

22. Zhang H., Plutzky J., Skentzos S., Morrison F., Mar P., Shubina M., Turchin A. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med. 2013;158(7):526-534. doi: 10.7326/0003-4819-158-7-201304020-00004.

23. Alekseeva I.A., Kolmakova T.E., Ezhov M.V Fixeddose combination of rosuvas-tatin + ezetimibe: ease of use, safety and efficacy. Meditsinskiy sovet = Medical Council. 2019;(16):21-26. (In Russ.) doi: 10.21518/2079-701X-2019-16-21-26.

24. Phan B.A., Dayspring T.D., Toth P.P. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415-427. doi: 10.2147/VHRM.S33664.

25. Pandor A., Ara R.M., Tumur I., Wilkinson AJ., Paisley S., Duenas A. et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009;265(5):568-580. doi: 10.1111/j.1365-2796.2008.02062.x.

26. Morrone D., Weintraub W.S., Toth P.P., Hanson M.E., Lowe R.S., Lin J. et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 2012;223(2):251-261. doi: 10.1016/j.atherosclerosis.2012.02.016.

27. Bays H.E., Davidson M.H., Massaad R., Flaim D., Lowe R.S., Tershakovec A.M., Jones-Burton C. Safety and Efficacy of Ezetimibe Added on to Rosuvastatin 5 or 10 mg Versus Up-Titration of Rosuvastatin in Patients With Hypercholesterolemia (the ACTE Study). Am J Cardiol. 2011;108(4):523-530. doi: 10.1016/j.amjcard.2011.03.079.

28. Ballantyne C.M., Weiss R., Moccetti T., Vogt A., Eber B., Sosef F., Duffield E. 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(5):673-680. doi: 10.1016/j.amjcard.2006.10.022.