Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 17 4 2022 10 31 168 179 EN Aziz Rezapour Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran. Samad Azari Research Center for Emergency and Disaster Resilience, Red Crescent Society of the Islamic Republic of Iran, Tehran, Iran. & Hospital Management Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran. Jalal Arabloo Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran. Pirhossein Kolivand Department of Health Economics, Faculty of Medicine, Shahed University, Tehran, Iran. Masoud Behzadifar Social Determinants of Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran. Negar Omidi Tehran Heart Center, Cardiovascular Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Ali Sarabi Asiabar Hospital Management Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran. Peyman Saberian Prehospital and Hospital Emergency Research Center, Tehran University of Medical Sciences, Tehran, Iran. Hamid Pourasghari Hospital Management Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran. Nicola Bragazzi Laboratory for industrial and applied mathematics (LIAM), Department of mathematics and statistics, York University, Toronto, Canada. Mehdi Mehrani Tehran Heart Center, Cardiovascular Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Shayan Shahi Tehran Heart Center, Cardiovascular Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Masih Tajdini Tehran Heart Center, Cardiovascular Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 2022 11 10 2022 12 28 Background: To assess the cost-effectiveness of sacubitril/valsartan compared with enalapril in patients with heart failure with reduced ejection (HFrEF). Methods: A systematic literature search was conducted searching in major electronic databases from inception to January 1, 2021. All relevant full economic evaluation studies of sacubitril/valsartan versus enalapril for the treatment of patients with HFrEF were identified using ad hoc search strategies. Mortality, hospital admissions, quality-adjusted life years (QALYs), life-years (LYQs), annual drug costs, total lifetime costs, and incremental cost-effectiveness ratio (ICER) were considered as the outcomes. The quality of the included studies was assessed using the CHEERS checklist. This study was conducted and reported in accordance with the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines. Results: The initial search yielded a pool of 1026 articles, of which 703 unique articles were screened, 65 full-text articles were assessed for eligibility and 15 studies finally included in the qualitative synthesis. Studies show that sacubitril/valsartan reduces mortality and hospitalization rate. The mean of death risk ratio and hospitalization were computed at 0.843 and 0.844, respectively. Sacubitril/valsartan produced higher annual and total lifetime costs. The lowest and highest lifetime costs for sacubitril/valsartan were found in Thailand ($4,756) and Germany ($118,815), respectively. The lowest ICER was reported in Thailand ($4857/QALY) and the highest in the USA ($143,891/QALY). Conclusion: Sacubitril/valsartan is associated with better outcomes and may be cost-effective compared to enalapril for the management of HFrEF. However, in developing countries such as Thailand, sacubitril-valsartan costs must be reduced to yield an ICER below the threshold. https://rhythm.tums.ac.ir/index.php/jthc/article/view/1752 https://rhythm.tums.ac.ir/index.php/jthc/article/download/1752/1026