Economic Evaluation of Sacubitril/Valsartan in Chronic Heart Failure Patients: A Markov Model Analysis in Iran
-
Mahmood Yousefi
,
Fatemeh Keshvari-Shad
,
Farhad Khalili
,
Jebraeil Farzi
,
Baharak Aghapour
,
Maryam Chenaghlou
Abstract
Background: Sacubitril/valsartan (Sac-Val) is recommended for patients with heart failure (HF) and reduced ejection fraction (HFrEF). This study aimed to evaluate the cost-effectiveness of Sac/Val in chronic HF patients in Iran.
Methods: A Markov model was constructed to assess the cost-effectiveness of Sac/Val and enalapril from a healthcare perspective over a 15-year time horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY). A discount rate of 3.5% was applied to both costs and outcomes, and a probabilistic sensitivity analysis was performed to evaluate the robustness of the results.
Results: The average costs of treating HF patients with Sac/Val and enalapril were 22,132,050,140 IRR (USD 77,442.3) and 143,043,859 IRR (USD 500.52), respectively, whereas the corresponding QALY values were 5.37 and 3.30, respectively. Sac/Val was more expensive and more effective than enalapril. The ICER was 10,635,189,214 IRR per QALY (37.06 USD/QALY), which was higher than the WHO-recommended threshold in terms of gross domestic product per capita in 2022. Sac/Val had a significant impact on increasing the QALY for HFrEF patients. At the proposed price, the cost per QALY value for Sac/Val exceeded the recommended threshold for the country.
Conclusion: Considering the country’s economic context, negotiating lower prices for Sac/Val would bring it to the top of the priority list for health services.
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2. Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, Adamopoulos S, Albert N, et al. Universal definition and classification of heart failure: a report of the heart failure society of America, heart failure association of the European society of cardiology, Japanese heart failure society and writing committee of the universal definition of heart failure. J Card Fail. 2021;27(4):387-413. doi: 10.1016/j.cardfail.2021.01.022
3. Rice H, Say R, Betihavas V. The effect of nurse-led education on hospitalisation, readmission, quality of life and cost in adults with heart failure. A systematic review. Patient Educ Couns. 2018;101(3):363-74. doi: 10.1016/j.pec.2017.10.002
4. Bratsos S. Efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor-neprilysin inhibitors in the treatment of chronic heart failure: a review of landmark trials. Cureus. 2019;11(1):e3913. doi: 10.7759/cureus.3913
5. Wachter R, Viriato D, Klebs S, Grunow SS, Schindler M, Engelhard J, et al. Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/ valsartan in Germany. Postgrad Med. 2018;130(3):308-16. doi: 10.1080/00325481.2018.1442090
6. Huusko J, Tuominen S, Studer R, Corda S, Proudfoot C, Lassenius M, et al. Recurrent hospitalizations are associated with increased mortality across the ejection fraction range in heart failure. ESC Heart Fail. 2020;7(5):2406-17. doi: 10.1002/ehf2.12792
7. Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, et al. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016;18(9):1193-202. doi: 10.1002/ejhf.548
8. Greenberg B. Angiotensin receptor-neprilysin inhibition (ARNI) in heart failure. Int J Heart Fail. 2020;2(2):73-90. doi: 10.36628/ijhf.2020.0002
9. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi: 10.1056/NEJMoa1409077
10. Morrow DA, Velazquez EJ, DeVore AD, Desai AS, Duffy CI, Ambrosy AP, et al. Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF trial. Circulation. 2019;139(19):2285-8. doi: 10.1161/circulationaha.118.039331
11. Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCagueK, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380(6):539-48. doi: 10.1056/NEJMoa1812851
12. Desai AS, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J, et al. Effect of sacubitril-valsartan vs enalapril on aortic stiffness in patients with heart failure and reduced ejection fraction: a randomized trial. JAMA. 2019;322(11):1077-84. doi: 10.1001/jama.2019.12843
13. Maddox TM, Januzzi JL Jr, Allen LA, Breathett K, Butler J, Davis LL, et al. 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;77(6):772-810. doi: 10.1016/j.jacc.2020.11.022
14. Sarrafzadegan N, Mohammmadifard N. Cardiovascular disease in Iran in the last 40 years: prevalence, mortality, morbidity, challenges and strategies for cardiovascular prevention. Arch Iran Med. 2019;22(4):204-10.
15. Lippi G, Sanchis-Gomar F. Global epidemiology and future trends of heart failure. AME Med J. 2020;5:15. doi: 10.21037/amj.2020.03.03
16. Golla MS, Hajouli S, Ludhwani D. Heart failure and ejection fraction. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2025.
17. Gaziano TA, Fonarow GC, Claggett B, Chan WW, Deschaseaux-Voinet C, Turner SJ, et al. Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction. JAMA Cardiol. 2016;1(6):666-72. doi: 10.1001/jamacardio.2016.1747
18. 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;165(10):681-9. doi: 10.7326/m16-0057
19. Liu XQ, He LS, Huang JQ, Xiong LJ, Xia C, Lao HY. Cost-effectiveness analyses of sacubitril-valsartan for heart failure. Heart Fail Rev. 2021;26(5):1119-30. doi: 10.1007/s10741-020-09956-6
20. Husereau D, Drummond M, Augustovski F, de Bekker-Grob E, Briggs AH, Carswell C, et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. MDM Policy Pract. 2022;7(1):23814683211061097. doi: 10.1177/23814683211061097
21. 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. doi: 10.1016/j.jchf.2016.02.007
22. Calvert MJ, Freemantle N, Cleland JG. The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study. Eur J Heart Fail. 2005;7(2):243-51. doi: 10.1016/j.ejheart.2005.01.012
23. Liang L, Bin-Chia Wu D, Abdul Aziz MI, Wong R, Sim D, Leong KT, et al. Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction. J Med Econ. 2018;21(2):174-81. doi: 10.1080/13696998.2017.1387119
24. Krittayaphong R, Permsuwan U. Cost-effectiveness analysis of sacubitril-valsartan compared with enalapril in patients with heart failure with reduced ejection fraction in Thailand. Am J Cardiovasc Drugs. 2018;18(5):405-13. doi: 10.1007/s40256-018-0288-x
25. Earla JR, Sansgiry SS. PCV31 Comparison of cost-effectiveness between sacubitril/valsartan and valsartan with enalapril in heart failure.Value Health. 2019;22:S124. doi: 10.1016/j.jval.2019.04.467
26. Zueger PM, Kumar VM, Harrington RL, Rigoni GC, Atwood A, DiDomenico RJ, et al. Cost-effectiveness analysis of sacubitril/ valsartan for the treatment of heart failure with reduced ejection fraction in the United States. Pharmacotherapy. 2018;38(5):520-30. doi: 10.1002/phar.2108
27. Gaziano TA, Fonarow GC, Velazquez EJ, Morrow DA, Braunwald E, Solomon SD. Cost-effectiveness of sacubitril-valsartan in hospitalized patients who have heart failure with reduced ejection fraction. JAMA
Cardiol. 2020;5(11):1236-44. doi: 10.1001/jamacardio.2020.2822
28. Wu Y, Tian S, Rong P, Zhang F, Chen Y, Guo X, et al. Sacubitrilvalsartan compared with enalapril for the treatment of heart failure: a decision-analytic Markov model simulation in China. Front Pharmacol. 2020;11:1101. doi: 10.3389/fphar.2020.01101
29. Chin KL, Zomer E, Wang BH, Liew D. Cost-effectiveness of switching patients with heart failure and reduced ejection fraction to sacubitril/valsartan: the Australian perspective. Heart Lung Circ. 2020;29(9):1310-7. doi: 10.1016/j.hlc.2019.03.007
30. 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. doi: 10.1016/j.jval.2016.10.015
31. Park SK, Hong SH, Kim H, Kim S, Lee EK. Cost-utility analysis of sacubitril/valsartan use compared with standard care in chronic heart failure patients with reduced ejection fraction in South Korea.
Clin Ther. 2019;41(6):1066-79. doi: 10.1016/j.clinthera.2019.04.031
2. Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, Adamopoulos S, Albert N, et al. Universal definition and classification of heart failure: a report of the heart failure society of America, heart failure association of the European society of cardiology, Japanese heart failure society and writing committee of the universal definition of heart failure. J Card Fail. 2021;27(4):387-413. doi: 10.1016/j.cardfail.2021.01.022
3. Rice H, Say R, Betihavas V. The effect of nurse-led education on hospitalisation, readmission, quality of life and cost in adults with heart failure. A systematic review. Patient Educ Couns. 2018;101(3):363-74. doi: 10.1016/j.pec.2017.10.002
4. Bratsos S. Efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor-neprilysin inhibitors in the treatment of chronic heart failure: a review of landmark trials. Cureus. 2019;11(1):e3913. doi: 10.7759/cureus.3913
5. Wachter R, Viriato D, Klebs S, Grunow SS, Schindler M, Engelhard J, et al. Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/ valsartan in Germany. Postgrad Med. 2018;130(3):308-16. doi: 10.1080/00325481.2018.1442090
6. Huusko J, Tuominen S, Studer R, Corda S, Proudfoot C, Lassenius M, et al. Recurrent hospitalizations are associated with increased mortality across the ejection fraction range in heart failure. ESC Heart Fail. 2020;7(5):2406-17. doi: 10.1002/ehf2.12792
7. Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, et al. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016;18(9):1193-202. doi: 10.1002/ejhf.548
8. Greenberg B. Angiotensin receptor-neprilysin inhibition (ARNI) in heart failure. Int J Heart Fail. 2020;2(2):73-90. doi: 10.36628/ijhf.2020.0002
9. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi: 10.1056/NEJMoa1409077
10. Morrow DA, Velazquez EJ, DeVore AD, Desai AS, Duffy CI, Ambrosy AP, et al. Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF trial. Circulation. 2019;139(19):2285-8. doi: 10.1161/circulationaha.118.039331
11. Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCagueK, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380(6):539-48. doi: 10.1056/NEJMoa1812851
12. Desai AS, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J, et al. Effect of sacubitril-valsartan vs enalapril on aortic stiffness in patients with heart failure and reduced ejection fraction: a randomized trial. JAMA. 2019;322(11):1077-84. doi: 10.1001/jama.2019.12843
13. Maddox TM, Januzzi JL Jr, Allen LA, Breathett K, Butler J, Davis LL, et al. 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;77(6):772-810. doi: 10.1016/j.jacc.2020.11.022
14. Sarrafzadegan N, Mohammmadifard N. Cardiovascular disease in Iran in the last 40 years: prevalence, mortality, morbidity, challenges and strategies for cardiovascular prevention. Arch Iran Med. 2019;22(4):204-10.
15. Lippi G, Sanchis-Gomar F. Global epidemiology and future trends of heart failure. AME Med J. 2020;5:15. doi: 10.21037/amj.2020.03.03
16. Golla MS, Hajouli S, Ludhwani D. Heart failure and ejection fraction. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2025.
17. Gaziano TA, Fonarow GC, Claggett B, Chan WW, Deschaseaux-Voinet C, Turner SJ, et al. Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction. JAMA Cardiol. 2016;1(6):666-72. doi: 10.1001/jamacardio.2016.1747
18. 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;165(10):681-9. doi: 10.7326/m16-0057
19. Liu XQ, He LS, Huang JQ, Xiong LJ, Xia C, Lao HY. Cost-effectiveness analyses of sacubitril-valsartan for heart failure. Heart Fail Rev. 2021;26(5):1119-30. doi: 10.1007/s10741-020-09956-6
20. Husereau D, Drummond M, Augustovski F, de Bekker-Grob E, Briggs AH, Carswell C, et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. MDM Policy Pract. 2022;7(1):23814683211061097. doi: 10.1177/23814683211061097
21. 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. doi: 10.1016/j.jchf.2016.02.007
22. Calvert MJ, Freemantle N, Cleland JG. The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study. Eur J Heart Fail. 2005;7(2):243-51. doi: 10.1016/j.ejheart.2005.01.012
23. Liang L, Bin-Chia Wu D, Abdul Aziz MI, Wong R, Sim D, Leong KT, et al. Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction. J Med Econ. 2018;21(2):174-81. doi: 10.1080/13696998.2017.1387119
24. Krittayaphong R, Permsuwan U. Cost-effectiveness analysis of sacubitril-valsartan compared with enalapril in patients with heart failure with reduced ejection fraction in Thailand. Am J Cardiovasc Drugs. 2018;18(5):405-13. doi: 10.1007/s40256-018-0288-x
25. Earla JR, Sansgiry SS. PCV31 Comparison of cost-effectiveness between sacubitril/valsartan and valsartan with enalapril in heart failure.Value Health. 2019;22:S124. doi: 10.1016/j.jval.2019.04.467
26. Zueger PM, Kumar VM, Harrington RL, Rigoni GC, Atwood A, DiDomenico RJ, et al. Cost-effectiveness analysis of sacubitril/ valsartan for the treatment of heart failure with reduced ejection fraction in the United States. Pharmacotherapy. 2018;38(5):520-30. doi: 10.1002/phar.2108
27. Gaziano TA, Fonarow GC, Velazquez EJ, Morrow DA, Braunwald E, Solomon SD. Cost-effectiveness of sacubitril-valsartan in hospitalized patients who have heart failure with reduced ejection fraction. JAMA
Cardiol. 2020;5(11):1236-44. doi: 10.1001/jamacardio.2020.2822
28. Wu Y, Tian S, Rong P, Zhang F, Chen Y, Guo X, et al. Sacubitrilvalsartan compared with enalapril for the treatment of heart failure: a decision-analytic Markov model simulation in China. Front Pharmacol. 2020;11:1101. doi: 10.3389/fphar.2020.01101
29. Chin KL, Zomer E, Wang BH, Liew D. Cost-effectiveness of switching patients with heart failure and reduced ejection fraction to sacubitril/valsartan: the Australian perspective. Heart Lung Circ. 2020;29(9):1310-7. doi: 10.1016/j.hlc.2019.03.007
30. 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. doi: 10.1016/j.jval.2016.10.015
31. Park SK, Hong SH, Kim H, Kim S, Lee EK. Cost-utility analysis of sacubitril/valsartan use compared with standard care in chronic heart failure patients with reduced ejection fraction in South Korea.
Clin Ther. 2019;41(6):1066-79. doi: 10.1016/j.clinthera.2019.04.031
| Files | ||
| Issue | Vol 9 No 4 (2025) | |
| Section | Articles | |
| DOI | https://doi.org/10.18502/htaa.v9i4.20662 | |
| Keywords | ||
| Cost-Utility Analysis Markov Model Heart Failure With Reduced Ejection Fraction Sacubitril/Valsartan | ||
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How to Cite
1.
Yousefi M, Keshvari-Shad F, Khalili F, Farzi J, Aghapour B, Chenaghlou M. Economic Evaluation of Sacubitril/Valsartan in Chronic Heart Failure Patients: A Markov Model Analysis in Iran. Health Tech Ass Act. 2025;9(4).
