, Volume 36, Issue 10, pp 1285–1296 | Cite as

Sacubitril/Valsartan (LCZ696): A Novel Treatment for Heart Failure and its Estimated Cost Effectiveness, Budget Impact, and Disease Burden Reduction in Germany

  • Afschin GandjourEmail author
  • Dennis A. Ostwald
Original Research Article



Heart failure affects over 1 million people in Germany and contributes to morbidity, mortality, and high healthcare costs. A recent large randomized controlled trial compared the novel compound sacubitril/valsartan (LCZ696) with the angiotensin-converting enzyme (ACE) inhibitor enalapril and found a 16% reduction in mortality hazard. In Germany, sacubitril/valsartan was launched at the beginning of 2016.


The purpose of this study was to conduct a post hoc analysis of the cost effectiveness, budget impact, and disease burden reduction of sacubitril/valsartan compared with ACE inhibitors for patients with heart failure from the perspective of the German social health insurance (SHI), based on the results of this trial.


A Markov (cohort) state transition model was constructed to simulate treatment over a remaining lifetime. Based on the Markov model, a dynamic population model was developed that projects the incidence, prevalence, mortality, and healthcare costs of heart failure in the SHI population from 2017 to 2060. The population model follows prevalent and incident cohorts over time. Each year a new cohort is added, while the existing cohorts age by 1 year or die. To test for sensitivity of results, a Monte Carlo simulation was run.


Based on the price negotiated between manufacturer and representatives of the SHI, the base-case incremental cost-effectiveness ratio (ICER) of sacubitril/valsartan versus ACE inhibitors is €23,401 per life-year gained (in 2018 Euros). At a price of zero, the cost-effectiveness ratio is already €9594 per life-year gained due to high background costs of heart failure. Annual budget impact and reduction of disease burden reach a maximum at 4–8 years after launch (€221 million and 2.9%, respectively, in the base case).


The ICER of sacubitril/valsartan is projected to be at or below the level of other accepted interventions for the treatment of asymptomatic to severe heart failure in Germany. Projected budget impact leads to an increase in SHI expenditures by < 0.04% per year.


Author contributions

AG was involved in model conceptualization, building, and validation, and wrote the first draft of the manuscript. DO was involved in model conceptualization and commented on the draft version of the manuscript.

Compliance with Ethical Standards

Data Availability Statement

All data generated or analyzed during this study are included in this published article.


This study was funded by Novartis Deutschland GmbH.


  1. 1.
    Ohlmeier C, Mikolajczyk R, Frick J, Prütz F, Haverkamp W, Garbe E. Incidence, prevalence and 1-year all-cause mortality of heart failure in Germany: a study based on electronic healthcare data of more than six million persons. Clin Res Cardiol. 2015;104(8):688–96.PubMedGoogle Scholar
  2. 2.
    Störk S, Handrock R, Jacob J, Walker J, Calado F, Lahoz R, Hupfer S, Klebs S. Epidemiology of heart failure in Germany: a retrospective database study. Clin Res Cardiol. 2017;106(11):913–22.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Pocock SJ, Ariti CA, McMurray JJ, Maggioni A, Køber L, Squire IB, Swedberg K, Dobson J, Poppe KK, Whalley GA, Doughty RN, Meta-Analysis Global Group in Chronic Heart Failure. Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies. Eur Heart J. 2013;34(19):1404–13.PubMedGoogle Scholar
  4. 4.
    Bundesamt Statistisches. Krankheitskostenrechnung. Wiesbaden: Statistisches Bundesamt; 2015.Google Scholar
  5. 5.
    McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K. Zile MR, PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993–1004.PubMedGoogle Scholar
  6. 6.
    Packer M, McMurray JJ, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile M, Andersen K, Arango JL, Arnold JM, Bělohlávek J, Böhm M, Boytsov S, Burgess LJ, Cabrera W, Calvo C, Chen CH, Dukat A, Duarte YC, Erglis A, Fu M, Gomez E, Gonzàlez-Medina A, Hagège AA, Huang J, Katova T, Kiatchoosakun S, Kim KS, Kozan Ö, Llamas EB, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires FJ, Refsgaard J, Rosenthal A, Senni M, Sibulo AS Jr, Silva-Cardoso J, Squire IB, Starling RC, Teerlink JR, Vanhaecke J, Vinereanu D. Wong RC, PARADIGM-HF Investigators and Coordinators. 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.PubMedGoogle Scholar
  7. 7.
    Lillyblad MP. Dual angiotensin receptor and neprilysin inhibition with sacubitril/valsartan in chronic systolic heart failure: understanding the New PARADIGM. Ann Pharmacother. 2015;49(11):1237–51.PubMedGoogle Scholar
  8. 8.
    Simpson J, Jhund PS, Silva Cardoso J, Martinez F, Mosterd A, Ramires F, Rizkala AR, Senni M, Squire I, Gong J, Lefkowitz MP, Shi VC, Desai AS, Rouleau JL, Swedberg K, Zile MR, McMurray JJ, Packer M. Solomon SD, PARADIGM-HF Investigators and Committees. Comparing LCZ696 with enalapril according to baseline risk using the MAGGIC and EMPHASIS-HF Risk Scores: an analysis of mortality and morbidity in PARADIGM-HF. J Am Coll Cardiol. 2015;66(19):2059–71.PubMedGoogle Scholar
  9. 9.
    Novartis Pharma GmbH. Sacubitril/Valsartan (Entresto®): Dossier zur Nutzenbewertung gemäß § 35a SGB V (Modul 4 A). Accessed 13 June 2018.
  10. 10.
    Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA. 1995;273(18):1450–6.PubMedGoogle Scholar
  11. 11.
    Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. General methods. Version 5.0. Köln: IQWiG. 2017.Google Scholar
  12. 12.
    Claggett B, Packer M, McMurray JJ, Swedberg K, Rouleau J, Zile MR, Jhund P, Lefkowitz M, Shi V, Solomon SD, PARADIGM-HF Investigators. Estimating the long-term treatment benefits of sacubitril-valsartan. N Engl J Med. 2015;373(23):2289–90.PubMedGoogle Scholar
  13. 13.
    Lauer-Fischer GmbH, Lauer-Taxe Arzneimittelpreise. Accessed 30 June 2018
  14. 14.
    Fischer KE, Stargardt T. The diffusion of generics after patent expiry in Germany. Eur J Health Econ. 2016;17(8):1027–40.PubMedGoogle Scholar
  15. 15.
    Kassenärztliche Bundesvereinigung. Einheitlicher Bewertungsmaßstab (EBM). Stand: 1. Quartal 2015. Berlin: Kassenärztliche Bundesvereinigung; 2018.Google Scholar
  16. 16.
    Institut für das Entgeltsystem im Krankenhaus. Fallpauschalen-Katalog 2015. Siegburg: InEK GmbH; 2018.Google Scholar
  17. 17.
    Management Consult Kestermann (2015). Gutachten zur ambulanten Notfallversorgung im Krankenhaus: Fallkostenkalkulation und Strukturanalyse. Accessed 29 May 2018.
  18. 18.
    Bundesamt Statistisches. Krankheitskostenrechnung. Bonn: Statistisches Bundesamt; 2010.Google Scholar
  19. 19.
    Trueman D, Kapetanakis V, Briggs A, Lewis E, Rouleau J, Solomon SD, Swedberg K, Zile MR, Packer M, McMurray JJV, Croft DC, Haroun R, Gielen V. Better health-related quality of life in patients treated with sacubitril/valsartan compared with enalapril, irrespective of NYHA class: Analysis of EQ-5D in PARADIGM-HF. Eur Heart J. 2017;38(Suppl 1):P3373.Google Scholar
  20. 20.
    Novartis Pharma GmbH. Sacubitril/Valsartan (Entresto®): Dossier zur Nutzenbewertung gemäß § 35a SGB V (Modul 3 A). Accessed 29 May 2018.
  21. 21.
    Jhund PS, Fu M, Bayram E, Chen CH, Negrusz-Kawecka M, Rosenthal A, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, McMurray JJ, Packer M, PARADIGM-HF Investigators and Committees. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF. Eur Heart J. 2015;36(38):2576–84.PubMedPubMedCentralGoogle Scholar
  22. 22.
    EuroQol Group. EuroQol–a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208.Google Scholar
  23. 23.
    Barendregt JJ. The half-cycle correction: banish rather than explain it. Med Decis Mak. 2009;29(4):500–2.Google Scholar
  24. 24.
    Bundesamt Statistisches. Allgemeine Sterbetafel 2010/12. Wiesbaden: Statistisches Bundesamt; 2015.Google Scholar
  25. 25.
    Kuntz K, Weinstein M. Modelling in economic evaluation. In: Drummond M, McGuire A, editors. Economic evaluation in health care: merging theory with practice. New York: Oxford University Press; 2001.Google Scholar
  26. 26.
    Bundesamt Statistisches. Bevölkerung: Deutschland, Stichtag, Altersjahre. Wiesbaden: Statistisches Bundesamt; 2015.Google Scholar
  27. 27.
    Statistisches Bundesamt. Bevölkerung Deutschlands bis 2060 – 13. koordinierte Bevölkerungsvorausberechnung. Wiesbaden: Statistisches Bundesamt; 2010.Google Scholar
  28. 28.
    Gampe J. Human mortality beyond age 110. In Supercentenarians. Berlin: Springer; 2010. p. 168–230.Google Scholar
  29. 29.
    Owan TE, Redfield MM. Epidemiology of diastolic heart failure. Prog Cardiovasc Dis. 2005;47(5):320–32.PubMedGoogle Scholar
  30. 30.
    Lewis EF, Lamas GA, O’Meara E, Granger CB, Dunlap ME, McKelvie RS, Probstfield JL, Young JB, Michelson EL, Halling K, Carlsson J, Olofsson B, McMurray JJ, Yusuf S, Swedberg K, Pfeffer MA, CHARM Investigators. Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM. Eur J Heart Fail. 2007;9(1):83–91.PubMedGoogle Scholar
  31. 31.
    Tiller D, Russ M, Greiser KH, Nuding S, Ebelt H, Kluttig A, Kors JA, Thiery J, Bruegel M, Haerting J, Werdan K. Prevalence of symptomatic heart failure with reduced and with normal ejection fraction in an elderly general population-the CARLA study. PLoS One. 2013;8(3):e59225.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Wachter R. Diastolic heart failure and multimorbidity. Dtsch Med Wochenschr. 2015;140(6):402–5.PubMedGoogle Scholar
  33. 33.
    Cassel D, Ulrich V. AMNOG-Check 2017: Gesundheitsökonomische Analysen der Versorgung mit Arzneimittel-Innovationen. Baden-Baden: Nomos Verlagsgesellschaft; 2017. p. 168.Google Scholar
  34. 34.
    Cavender MA, Norhammar A, Birkeland KI, Jørgensen ME, Wilding JP, Khunti K, Fu AZ, Bodegård J. Blak BT, Wittbrodt E, Thuresson M, Fenici P, Hammar N, Kosiborod M, CVD-REAL Investigators and StudyGroup. SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL. J Am Coll Cardiol. 2018;71(22):2497–506.PubMedGoogle Scholar
  35. 35.
    Sullivan SD, Mauskopf JA, Augustovski F, Jaime Caro J, Lee KM, Minchin M, Orlewska E, Penna P, Rodriguez Barrios JM, Shau WY. Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value Health. 2014;17(1):5–14.PubMedGoogle Scholar
  36. 36.
    Aidelsburger P, Grabein K, Klauss V, Wasem J. Cost-effectiveness of cardiac resynchronization therapy in combination with an implantable cardioverter defibrillator (CRT-D) for the treatment of chronic heart failure from a German health care system perspective. Clin Res Cardiol. 2008;97(2):89–97.PubMedGoogle Scholar
  37. 37.
    Gandjour A, Holler A, Adarkwah CC. Cost-effectiveness of implantable defibrillators after myocardial infarction based on 8-year follow-up data (MADIT II). Value Health. 2011;14(6):812–7.PubMedGoogle Scholar
  38. 38.
    Sandhu AT, Ollendorf DA, Chapman RH, Pearson SD, Heidenreich PA. Cost-effectiveness of sacubitril-valsartan in patients with heart failure with reduced ejection fraction. Ann Intern Med. 2016 Nov 15;165(10):681–9.PubMedGoogle Scholar
  39. 39.
    Gaziano TA, Fonarow GC, Claggett B, Chan WW, Deschaseaux-Voinet C, Turner SJ, Rouleau JL, Zile MR, McMurray JJ, Solomon SD. Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction. JAMA Cardiol. 2016;1(6):666–72.PubMedGoogle Scholar
  40. 40.
    King JB, Shah RU, Bress AP, Nelson RE, Bellows BK. Cost-effectiveness of sacubitril-valsartan combination therapy compared with enalapril for the treatment of heart failure with reduced ejection fraction. JACC Heart Fail. 2016;4(5):392–402.PubMedGoogle Scholar
  41. 41.
    van der Pol S, Degener F, Postma MJ, Vemer P. An economic evaluation of sacubitril/valsartan for heart failure patients in the Netherlands. Value Health. 2017;20(3):388–96.PubMedGoogle Scholar
  42. 42.
    Corro Ramos I, Versteegh MM, de Boer RA, Koenders JM, Linssen GC, Meeder JG, Rutten-van Mölken MP. Cost-effectiveness of the angiotensin receptor neprilysin inhibitor sacubitril/valsartan for patients with chronic heart failure and reduced ejection fraction in the Netherlands: a country adaptation analysis under the former and current Dutch Pharmacoeconomic Guidelines. Value Health. 2017;20(10):1260–9.Google Scholar
  43. 43.
    National Institute for Health and Care Excellence. Final appraisal determination: sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction. Issue date: March 2016.Google Scholar
  44. 44.
    Neumann PJ, Sanders GD, Russell LB, Siegel JE, Ganiats TG, editors. Cost-effectiveness in health and medicine. 2nd ed. New York: Oxford University Press; 2016.Google Scholar
  45. 45.
    Grimm SE, Dixon S, Stevens JW. When future change matters: modeling future price and diffusion in health technology assessments of medical devices. Value Health. 2016;19(6):720–6.PubMedGoogle Scholar
  46. 46.
    Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC, Ikonomidis JS, Khavjou O, Konstam MA, Maddox TM, Nichol G, Pham M, Piña IL, Trogdon JG, American Heart Association Advocacy Coordinating Committee; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Stroke Council. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6(3):606–19.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Frankfurt School of Finance and ManagementFrankfurt am MainGermany
  2. 2.WifORDarmstadtGermany

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