PHARMACOECONOMIC ANALYSIS OF CHRONIC HEART FAILURE DRUG THERAPY IN PATIENTS WITH COMORBID CONDITIONS

Aim. To perform pharmacoeconomic analysis of CHF therapy with supramolecular sacubitril/valsartan complex compared to routine therapy in patients with diabetes type 2 and ACE inhibitor intolerance within context of Russian healthcare system.

Material and methods. A Markov model based on Russian Standards of treatment and clinical practice results was built. Cost-effectiveness analysis was done by comparing two patient groups of 1000 people each. Budget impact analysis required 27,451 simulated patients. Randomized controlled clinical trials results of sacubitril/valsartan vs. routine practice were used as source of efficacy and safety data. Time horizon was set at 3 years. Quality Adjusted Life Years (QALY) were used as effectiveness. Single-factor sensitivity analysis (SA) was used to ensure the results are robust to changes in market situation.

Results. Cost-effectiveness ratio for sacubitril/valsartan is 301,145.7 rub. per QALY while cost-effectiveness ratio for routine practice is 510,621 rub. Budget impact analysis results indicate that during three years, in case of sacubitril/valsartan usage budgetary burden can be reduced by more than 220,000 rubles per patient and leads to savings of more than six billion rubles in terms of the whole population. Sensitivity analysis has confirmed the robustness of results.

Conclusion. These results indicate benefits of sacubitril/valsartan using for CHF patients with type 2 diabetes and ACE inhibitor intolerance and justify inclusion of this drug into reimbursement lists that allow to reduce risk of hospitalization, lethal outcomes and budget of healthcare system.

1. Chen J, Normand SL, Wang Y, Krumholz HM. National and regional trends in heart failure hospitalization and mortality rates for Medicare beneficiaries, 1998-2008. JAMA. 2011;306(15):1669-78. doi: 10.1001/jama.2011.1474.

2. Ageev F.T., Belenkov U.N., Fomin I.V. et al. Incidence of chronic heart failure in European part of the Russian Federation – data from EPOCHA-HSN study. Zhurnal Serdechnaja Nedostatochnost'. 2006;7(1):112-5. (In Russ.)

3. Belenkov U.N., Fomin I.V., Mareev V.U. et al. Prevalence of chronic heart failure un European part of Russian Federation – data from EPOCHA-HSN study (part 2). Zhurnal Serdechnaja Nedostatochnost'. 2006;7(3):3-7. (In Russ.)

4. Modern problems of medical support of patients with cardiological diseases (based on results of project for acquisition of data on quality and availability of medical assistance for cardiological patients). Analytical Note. Moscow: Federal Service of Government Statistics, 2017. Available at: http:.www.gks.ru/wps/wcm/connect/rosstat_main/rosstat/ru/statistics/population/healthcar/ Checked on 10.02.2018. (In Russ.)

5. Sitnikova M.U. Chronic heart failure: epidemiology and planning perspectives. Zhurnal Serdechnaja Nedostatochnost'. 2012;6(74):372-6. (In Russ.)

6. Butler J., Kalogeropoulos A. Worsening heart failure hospitalization epidemic. Journal of the American College of Cardiology. 2008;52(6):435–7. doi:10.1016/j.jacc.2008.04.037.

7. Ageev F.T., Danielyan M.O., Mareev V.U. et al Patients with chronic heart failure In Russian outpatient care practice: peculiarities of population, diagnosis and treatment (based on EPOCHA-O-HSN data). Zhurnal Serdechnaja Nedostatochnost'. 2004;5(1):1-7.

8. Lazarev P.V., Alexandria L.G., Shavarov A.A. Clinical fatal outcome prognosis among patients with acute decompensation of chronic heart failure. Kardiologiia. 2013;(2):19-24. (In Russ.)

9. Ramani G.V., Uber P.A., Mehra M.R. Chronic Heart Failure: Contemporary Diagnosis and Management. Mayo Clinic Proceedings. 2010;85(2):180-95. doi:10.4065/mcp.2009.0494.

10. Lloyd-Jones D., Adams R., Carnethonet M. et al. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):e21-181. doi: 10.1161/CIRCULATIONAHA.108.191261.

11. Roger V. L., Weston S. A., Redfield M. M. et al. Trends in heart failure incidence and survival in a communitybased population. JAMA. 2004;292(3):344–50. doi:10.1001/jama.292.3.344.

12. Fala L. Entresto (Sacubitril/Valsartan): First-in-Class Angiotensin Receptor Neprilysin Inhibitor FDA Approved for Patients with Heart Failure. American Health & Drug Benefits. 2015;8(6):330-4.

13. Vilela-Martin J.F. Spotlight on valsartan–sacubitril fixed-dose combination for heart failure: the evidence to date. Drug Design, Development and Therapy. 2016;10:1627-39. doi: 10.2147/DDDT.S84782.

14. Desai AS, Claggett BL, Packer M et al. PARADIGM-HF Investigators. Influence of sacubitril/valsartan (LCZ696) on 30-Day readmission after heart failure hospitalization. J Am Coll Cardiol. 2016;68:241–8 doi: 10.1016/j.jacc.2016.04.047.

15. McMurray J.J., Packer M., Desai A.S., PARADIGM-HF Investigators and Committees Angiotensinneprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004. doi: 10.1056/NEJMoa1409077.

16. Packer M, McMurray JJ, Desai AS, et al. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015;131(1):54–61. doi: 10.1161/CIRCULATIONAHA.114.013748.

17. Seferovic J.P., Claggett B, Seidelmann S.B., et al. Effect of sacubitril/valsartan vs enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial. Lancet Diabetes Endocrinol. 2017;5(5):333–40 doi: 10.1016/S2213-8587(17)30087-6.

18. Zhuravleva M.V., Kukes V.G., Prokofiev A.B. et al Clinico-economic analysis of use of innovative Sacubitril/ valsartan complex for treatment of patients suffering from chronic heart failure with reduced ejection fraction. Russkij Medicinskij Zhurnal. 2017;4:282-9. (In Russ.)

19. Industry standard "Clinical and economic research. General provisions ≫Order of the Ministry of Health of the Russian Federation from 27.05.2002 №163 together with the stop 91500.14.0001-2002. Available at: http://www.healtheconomics.com/index.php?Option=com_content&view=article&id=300:-q-q&catid=55:2009-05-29-19-56-44&Itemid=104. Checked on 11.02.2018. (In Russ.)

20. Methodical recommendations of FGBU "CECMPS" of the Ministry of Health of Russia for conducting a comparative clinical and economic evaluation of a medicinal product. Available at: https://rosmedex.ru/25-12-16/. Checked on 12.10.2017. (In Russ.)

21. Methodical recommendations of FGBU "CECMPS" of the Ministry of Health of Russia to assess the impact on the budget as part of the implementation of the Program of state guarantees for free provision of medical care to citizens. Available at: https://rosmedex.ru/25-12-16/. Checked on 12.10.2017. (In Russ.)

22. The federal law "On the Federal Budget for 2018 and the Planning Period 2019 and 2020" of 05.12.2017 N 362-FZ. Available at: http://www.consultant.ru/document/cons_doc_LAW_284360/. Checked on 10.12.2017]. (In Russ)

23. Serenko K.A., Pokrovsky V.E. Preliminary results of research regarding effects of introduction of Sacubitril/ valsartan complex on healthcare resource utilization. Kachestvennaja Klinicheskaja Praktika. 2017;4:53-7. (In Russ.)

24. Heran B.S., Musini V.M., Bassett K., et al. Angiotensin receptor blockers for heart failure. Cochrane Database Syst Rev. 2012;4 doi: 10.1002/14651858.CD003040.pub2.

25. Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349(20):1893–906. doi: 10.1056/NEJMoa032292.

26. Chronic heart failure. Clinical guidelines. Available at: http://www.consultant.ru/document/cons_doc_LAW_284360/. Checked on 10.12.2017]. (In Russ.)

27. National guidelines for the diagnosis and treatment of chronic heart failure (fourth revision). Zhurnal Serdechnaja Nedostatochnost'. 2013;14(7):1-24. (In Russ.)

28. Swedberg K., Komajda M., Bohm M., et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomized placebo-controlled study . Lancet. 2010;376:875–85. doi: 10.1016/S01406736(10)61198-1.

29. Safavi K.C., Dharmarajan K, Kim N, et al. Variation exists in rates of admission to intensive care units for heart failure patients across hospitals in the United States. Circulation. 2013;127(8):923–9 doi: 10.1161/CIRCULATIONAHA.112.001088.

30. Corrao G, Ghirardi A, Ibrahim B, et al. Shortand long-term mortality and hospital readmissions among patients with new hospitalization for heart failure: A population-based investigation from Italy. Int J Cardiol. 2015;181:81-7. doi: 10.1016/j.ijcard.2014.12.004.

31. Adams K.F., Fonarow G.C., Emerman C.L., et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: Rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2005;149:209–16. doi: 10.1016/j.ahj.2004.08.005.

32. Decree of the Government of the Russian Federation of 23 October 2017 No. 2323-r. Available on: https://rg.ru/2017/10/25/pravitelstvo-rasp2323-site-dok.html. Checked on 13.02.2018. (In Russ.)

33. Tariff agreement for the payment of medical assistance provided under the territorial program of compulsory medical insurance of the city of Moscow for 2018 from December 29, 2017, with attachments, Moscow. Available at: http: .www.mgfoms.ru/strahovye-kompanii/tarifi. Checked on 25.01.2018. (In Russ.)

34. Teerlink JR, Cotter G, Davison BA, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial . Lancet. 2013;381:2939. doi: 10.1016/S0140-6736(12)61855-8.

35. Belousov D.U., Afanasyeva E.V., Basic insulin analogues in Type 2 diabetes control – economic aspects. Kachestvennaja Klinicheskaja Praktika. 2014,(1):3-13. (In Russ.)

36. Federal Law "On the Budget of the Federal Fund of Mandatory Medical Insurance for 2018 and for the Planning Period 2019 and 2020" of 05.12.2017 N 368-FZ. Available at: http://www.consultant.ru/document/cons_doc_LAW_284131/. Checked on 13.02.2018. (In Russ.)

37. Fomin I.V., Mareev V.U., Ageev F.T., et al. Diabetes as etiological cause of chronic heart failure in European part of Russian Federation (EPOCHA-HSN trial, hospital stage). Zhurnal Serdechnaja Nedostatochnost'. 2012;13(1):3-8. (In Russ.)

38. Mareev V.U., Danielyan M.O., Belenkov U.N. On behalf of EPOCHA-O-HSN workgroup. Comparative characteristics of chronic heart failure parameters relative to ejection fraction magnitude based on Russian multicenter research effort EPOCHA-O-HSN. Zhurnal Serdechnaja Nedostatochnost' 2006;7(4):164-71. (In Russ.)

39. Kostis JB, Shelton B, Gosselin G, et al. Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators. Am Heart J. 1996;131(2):350-5. doi: 10.1016/S0002-8703(96)90365-8.

40. Yagudina R.I., Serpik V.G., Ugrehelidze D.T. Methodological basics of budget impact analysis. Pharmacoeconomics: theory and practice. 2015;3(4):5-8. (In Russ.)

41. Yagudina R.I., Kulikov A.Yu., Serpik V.G. Discounting in the conduct of pharmacoeconomic research. Farmakojekonomika. 2009;4:10-3. (In Russ.)

42. Belousov U.B., Belousov D.U. “Basicsofpharmacoeconomicresearch” Training Manual. M 2000. Moscow: RGMU national fund for assisting scientific and clinical research; 2000. (In Russ.)