Economic losses due to low coverage of lipid-lowering therapy in patients with cardiovascular diseases in the Russian Federation

Aim. To assess the economic burden associated with the absence of lipid-lowering therapy (LLT) in patients with cardiovascular diseases (CVD) and hypercholesterolemia (HCS) in the Russian population in 2016, including direct costs of the health care system  and indirect economic losses due to premature death, absenteeism and disability.

Material and methods. The calculation includes data  from local population-based studies (prevalence of HCS, treatment coverage and efficiency), as well as Russian statistics on CVD for 2016. Population attributive risk (PAR) was determined, which reflected the incidence of excessive morbidity associated with the lack of HCS therapy in developing CVD for the Russian population, based  on LDL cholesterol level. Direct and indirect components of economic burden associated with the absence of LLT have been calculated, as well as the number of deaths with the calculation of "lost years of potential life" lacking to reach the age of 72 years, and losses associated with premature mortality in the economically active age. Indirect costs (economic losses) included non-received gross domestic product (GDP) due to premature mortality and disability in economically active age and loss of earnings due to temporary disability (TD). To estimate the indirect costs,  the number of people of the working age  with permanent disability in each  of the disability groups  has  been  calculated. The indirect costs  due  to temporary disability were  calculated as payments of salary including for days  of incapacity for work multiplied by the number of days of TD according the Russian statistics data.

Results. The absence of LLT  in people with HCS increases the  risk of CVD related mortality by one  third, death due  to cerebrovascular diseases, including stroke,  by more than a half. PAR was estimated to be 17% for CVD mortality in general, 26% for cerebrovascular diseases. Contribution of HCS and  the  lack of LLT to morbidity is 29% for ischemic heart  disease (IHD), 20% for myocardial infarction. Outpatient calls take  the  first place among all out-patient care statistics, and those  associated with IHD are in the leading position among them.  Hospitalization takes the second  place. The absence of LLT caused  the loss of more than 400,000 years of life in economically active age. The direct costs are determined by expenses for hospitalizations in the presence of IHD. The share of direct costs for hospitalizations is 86%, while in the presence of cerebrovascular diseases it is 76.8%. Payments for disability allowance, which refers to direct non-medical costs, exceed 154 million Russian rubles (RUR) for IHD and 104 million RUR for cerebrovascular diseases. The biggest share  of economic burden associated with the lack of LLT in individuals with this risk factor  is accounted for indirect economic losses: about 507 billion RUR in IHD, of which more  than  90  billion RUR are  associated with myocardial infarction. The costs associated with cerebrovascular diseases make up over 305 billion RUR, the vast majority of which is due to stroke: over 248 billion RUR. Due to the low LLT coverage in the Russian Federation, the economic burden associated with its absence is over 80% of the calculated HCS related losses in total.

Conclusion. Economic burden of the lack of LLT in HCS patients is calculated as 530 billion RUR, which is about 0.6% of GDP in 2016, and the largest part of expenditures is related to IHD. The increased awareness of HCS and its improved control with increasing treatment coverage will make possible to lower cholesterol values at the population level, which will also reduce  the economic burden of this risk factor for CVD.

1. McAloon C.J. et al. The changing face of cardiovascular disease 2000-2012: An analysis of the world health organisation global health estimates data. Int J Cardiol. 2016;224:256-64. doi:10.1016/j.ij-card.2016.09.026.

2. Konstantinov V.V., Deev A.D., Balanova Yu.A, et al. The cardiovascular risk profile and its contribution to survival in Moscow men and women aged 35-64 years. Profilakticheskaya Meditsina. 2013;16(1):3-7. (In Russ.).

3. Bruthans J., Cífková R., Lánská V. et al. Explaining the decline in coronary heart disease mortality in the Czech Republic between 1985 and 2007. European Journal of Preventive Cardiology. 2012;21(7):829-39. doi:10.1177/2047487312469476.

4. Ford E.S., Ajani U.A., Croft J.B., et al. Explaining the decrease in US deaths from coronary disease, 1980-2000. N Engl J Med. 2007;356(23):2388-98. doi:10.1056/NEJMsa053935.

5. Kontsevaya A.V., Balanova Y.A., Imaeva A.E., et al. Economic burden of hypercholesterolemia in the Russian Federation. Rational Pharmacotherapy in Cardiology. 2018;14(3):393-401 (In Russ.). doi:10.20996/1819-6446-2018-14-3-393-401.

6. Metelskaya V.A., Shalnova S.A., Deev A.D. Analysis of atherogenic dyslipidemias prevalence among population of Russian Federation (results of the ESSE-RF Study). Profilakticheskaya Meditsina. 2016;19(1):15-23 (In Russ.). doi:10.17116/profmed201619115-23.

7. Shalnova S.A., Deev A.D., Metelskaya V.A. et al. Awareness and treatment specifics of statin therapy in persons with various cardiovascular risk: the study ESSE-RF. Cardiovascular Therapy and Prevention. 2016;15(4):29-37. (In Russ.). doi:10.15829/1728-8800-2016-4-29-37.

8. Lindgren P., Eriksson J., Buxton M. et al. The economic consequences of non-adherence to lipid-lowering therapy: Results from the Anglo-Scandinavian-Cardiac Outcomes Trial. International Journal of Clinical Practice. 2010;64(9):1228-34. doi:10.1111/j.1742-1241.2010.02445.x.

9. WHO Mortality Database. WHO: World Health Organization; 2014. [cited by Oct 21, 2018] Available from: http://www.who.int/healthinfo/mortality_data/en/.

10. Russian database on fertility and mortality. [cited by Oct 21, 2018] Available from: http://demogr.nes.ru/ru/demogr_indicat/data_description (In Russ.).

11. Filippov E.V., Balanova Yu.A. Dyslipidemia and its relationship with chronic non-communicable diseases (according to the MERIDIAN-RO study). Medicinskij Sovet. 2015;12:104-10. (In Russ.).

12. Kontsevaya A.V., Drapkina O.M., Balanova Y.A. et al. Economic Burden of Cardiovascular Diseases in the Russian Federation in 2016. Rational Pharmacotherapy in Cardiology. 2018;14(2):156-66. (In Russ.). doi:10.20996/1819-6446-2018-14-2-156-166.

13. Government Decision №1382 of 19 December 2015 «On the Programme of State guarantees for providing citizens of the Russian Federation with free medical care for 2016». [cited by Oct 21, 2018]. Available from: http://www.garant.ru/products/ipo/prime/doc/71189846/ (In Russ.).

14. The demographic yearbook of Russia. Statistical handbook. Moscow: Rosstat; 2017 (In Russ.).

15. Government Decision №247 of 18.03.2015 “On the approval of the indexation coefficient from 01/04/2015 of social pensions” [cited by Oct 21, 2018]. Available from: http://base.garant.ru/70913974/ (In Russ.).

16. Government Decision №192/323н/45н/113 of 10 April 2012 "On the approval of the methodology for calculating economic losses from mortality, morbidity and disability of the population" [cited by Oct 21, 2018]. Available from: http://www.garant.ru/products/ipo/prime/doc/70070542/.

17. Gutierrez J., Ramirez G., Rundek T., et al. Statin Therapy in the Prevention of Recurrent Cardiovascular Events. Cochrane Database Syst Rev. 2013(1):909-19. doi:10.1001/archinternmed.2012.2145.

18. Taylor F., Ward K., Moore T. H. et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):CD004816. doi:10.1002/14651858.CD004816.pub5.

19. Conly J., Clement F., Tonelli M., et al. Cost-effectiveness of the use of low- and high-potency statins in people at low cardiovascular risk. CMAJ. 2011;183(16):1189-202. doi:10.1503/cmaj.101281.

20. Ford E.S., Capewell S. Trends in Total and Low-Density Lipoprotein Cholesterol among U.S. Adults: Contributions of Changes in Dietary Fat Intake and Use of Cholesterol-Lowering Medications. PLoS One. 2013;8(5):1-8. doi:10.1371/journal.pone.0065228.

21. Guzman-Castillo M., Ahmed R., Hawkins N. et al. The contribution of primary prevention medication and dietary change in coronary mortality reduction in England between 2000 and 2007: a modelling study. BMJ Open. 2015;5(1):e006070. doi:10.1136/bmjopen-2014-006070.

22. Wang W., Zhang B. Statins for the prevention of stroke: A meta-analysis of randomized controlled trials. PLoS One. 2014;9(3):e92388. doi:10.1371/journal.pone.0092388.

23. Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267-78. doi:10.1016/S0140-6736(05)67394-1.

24. Wang T.Y., Newby L.K., Chen A.Y. et al. Hypercholesterolemia paradox in relation to mortality in acute coronary syndrome. Clin Cardiol. 2009;32(9):E22-8. doi:10.1002/clc.20518.

25. Shepel R.N. Cholesterol paradox in patients with chronic cardiac insufficiency modern state of the problem. Meditsinskiy Sovet. 2016;13:61-5. (In Russ.). doi:10.21518/2079-701X-2016-13-61-65.

26. Bundhun P.K., Wu Z.J., Chen M.H. Impact of Modifiable Cardiovascular Risk Factors on Mortality After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of 100 Studies. Medicine (Baltimore). 2015,94(50):e2313. doi:10.1097/MD.0000000000002313

27. Mensah G.A., Wei G. S., Sorlie, P. D. et al. Decline in Cardiovascular Mortality: Possible Causes and Implications. Circulation Research. 2017;120(2):366-80. doi:10.1161/CIRCRESAHA.116.309115.

28. Hopstock L.A., Bønaa K. H., Eggen A. E., et al. Longitudinal and secular trends in total cholesterol levels and impact of lipid-lowering drug use among Norwegian women and men born in 1905-1977 in the population-based Tromsø Study 1979-2016. BMJ Open. 2017;7(8):e015001. doi:10.1136/bmjopen-2016-015001.

29. Ezhov M.V. Recent progress in the management of atherosclerosis and hyperlipidemia. Meditsinskiy Sovet. 2017;7:5-10. (In Russ.). doi:10.21518/2079-701X-2017-7-5-10.

30. Shalnova S.A., Vilkov V.G., Metelskaya V.A. et al. Thirty-year changes in average blood lipids levels in populations of the Russian Federation and the USA. Rational Pharmacotherapy in Cardiology. 2018;14(1):4-11 (In Russ.). doi:10.20996/1819-6446-2018-14-1-4-11.

31. Voevoda M.I., Kovalkova N.A., Ragino Yu.I. et al. Prevalence of metabolic syndrome in 25-45-year-old Nov osibirsk dwellers. Ter Arkhiv. 2016;88(10):51-6 (In Russ.). doi:10.17116/terarkh2016881051-56.

32. Serebryakova V.N., Trubacheva I.A., Kaveshnikov V.S., et a l. Abnormalities of lipid and carbohydrate metabolism in population of female intellectual workers. Siberian Medical Journal. 2014;29(2):79-84. (In Russ.). doi10.29001/2073-8552-2014-29-2-79-84.

33. Wadhera R.K., Steen D. L., Khan I., et a l. A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. J Clin Lipidol. 2016;10(3):472-89. doi:10.1016/j.jacl.2015.11.010.

34. Ershova A.I., Meshkov A.N., Yakushin S.S. 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. (In Russ.). doi:10.20996/1819-6446-2014-10-6-612-616.

35. Smetnev S.A., Ershova A.I., Bogdanova R.S. et al. The Effectiveness of Outpatient and Hospital Lipid-lowering Therapy in Patients with High and Very High Cardiovascular Risk during 2011-2015. Rational Pharmacotherapy in Cardiology. 2016;12(6):622-30. (In Russ.). doi:10.20996/1819-6446-2016-12-6-622-630.

36. Eriksson M., Forslund A.S., Jansson J.H., et al. Greater decreases in cholesterol levels among individuals with high cardiovascular risk than among the general population: The northern Sweden MONICA study 1994 to 2014. Eur Heart J. 2016;37(25):1985-92. doi:10.1093/eurheartj/ehw052.

37. Reiner Ž., De Backer G., Fras Z. et al. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries - Findings from the EUROASPIRE IV survey. Atherosclerosis. 2016;246:243-50. doi:10.1016/j.atherosclerosis.2016.01.018.

38. Stam Slob M.C., van der Graaf Y., Greving J.P. et al. Cost-effectiveness of intensifying lipid-lowering therapy with statins based on individual absolute benefit in coronary artery disease patients. J Am Heart Assoc. 2017;6(2). pii: e004648. doi:10.1161/JAHA.116.004648.

39. Gilyarevsky S.R., Orlov V.A., Sycheva E.Yu. Economical strategies of treatment in cardiology. Emergency Medicine. 2007;3(10):56-65 (In Russ.).

40. Belousov D.Yu., Afanasyeva E.V., Beketov A.S., et al. Forecasting the effect of statins on direct medical costs in secondary prevention in patients with a high risk of developing cardiovascular diseases. Good Clinical Practice. 2011;1:97-115. (In Russ.).

41. Blackburn D.F., Dobson R.T., Blackburn J.L. et al. Cardiovascular morbidity associated with nonadherence to statin therapy. Pharmacotherapy. 2005;25(8):1035-43. doi:10.1592/phco.2005.25.8.1035.

42. Foody J.M., Joyce A.T., Rudolph A.E. et al. Cardiovascular outcomes among patients newly initiating atorvastatin or simvastatin therapy: A large database analysis of managed care plans in the United States. Clin Ther. 2008;30(1):195-205. doi:10.1016/j.clinthera.2008.01.00.

43. Wei L., Wang J., Thompson P. et al. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart. 2002;88(3):22933. doi:10.1136/heart.88.3.229.

44. Ridker P.M., Morrow D.A., Rose L.M., et al. Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: An analysis of the PROVE-IT TIMI-22 trial. JACC. 2005;45(10):1644-8. doi:10.1016/j.jacc.2005.02.080.

45. Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet. 2007;370(9602):1829-39. doi:10.1016/S0140-6736(07)61778-4.

46. Ziryanov S.K., Diakov I.N. Expected economic effect of the alirocumab administration in patients with hypercholesterolemia and high cardiovascular risk. Clinical Pharmacology and Therapy. 2018;27(1):90-6 (In Russ.).