OBJECTIVES: PARADIGM-HF, a phase III trial conducted in patients with heart failure with reduced ejection fraction (HFrEF), showed that sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, provided incremental cardiovascular and overall survival benefit compared with enalapril. This analysis aims to quantify the number of all-cause deaths that potentially could be avoided with optimal usage of sacubitril/valsartan in the treatment of HFrEF in Brazil. METHODS: Data from Instituto Brasileiro de Geografia e Estatística was used to quantify the target population. A literature review was conducted to determine the prevalence of HF, the proportion of NYHA Class II-IV and finally, the proportion of HFrEF patients. The number needed to treat (NNT) to avoid one death due to any cause, standardized to 12 months, was derived from the PARADIGM-HF trial. The number of all-cause deaths that might be potentially prevented or postponed as a result of treatment with sacubitril/valsartan was estimated along with multiple-way sensitivity analysis. The main outcome measure was all-cause mortality. RESULTS: The 2017 population (≥20 years) in Brazil was estimated at 144,323,520 and the estimated prevalence of HF was 2%, which was applied to determine the number of HF patients. The percentage of diagnosed HF patients was 60%. Of these, 85% were NYHA Class II-IV; 41% of these patients had HFrEF. This equated to 603,561 patients with HFrEF NYHA class II-IV. Finally, absolute reduction in all-cause mortality in PARADIGM-HF was 2.8% over an average follow-up time of 27 months. This translates into a NNT, standardized to 12 months, of 80.3; thus, optimal usage of sacubitril/valsartan therapy was estimated to prevent 7,516 deaths each year. CONCLUSIONS: The findings suggest that a substantial number of deaths could potentially be prevented by optimal implementation of sacubitril/valsartan therapy. Implementation of sacubitril/valsartan into routine clinical practice is important, and may substantially improve clinical outcomes among HFrEF patients in Brazil.