IJCS | Volume 33, Nº3, May / June 2020

280 1. Dunlay SM, Roger VL, RedfieldMM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14(10):591-602. 2. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891-975. 3. Comitê Coordenador da Diretriz de Insuficiência Cardíaca; Rohde LEP, Montera MW, Bocchi EA, Clausell NO, Albuquerque DC de, Rassi S, et al. Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda. Arq Bras Cardiol .111(3):436-539. 4. Lam CSP, Gamble GD, Ling LH, Sim D, Leong KTG, Yeo PSD, et al. Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study. Eur Heart J. 2018;39(20):1770-80. 5. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, RedfieldMM. Trends in Prevalence and Outcome of Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2006;355(3):251–9. 6. Gerber Y, Weston SA, Redfield MM, Chamberlain AM, Manemann SM, Jiang R, et al. A contemporary appraisal of the heart failure epidemic in Olmsted County, Minnesota, 2000 to 2010. JAMA Intern Med. 2015;175(6):996-1004. References Saraiva & Oliveira PARAGON-HF: lessons learned and perspectives Int J Cardiovasc Sci. 2020; 33(3):278-281 Viewpoint values. In addition, the therapeutic effects of sacubitril/ valsartan, compared with a renin-angiotensin system (RAS) inhibitor alone, vary across the continuum of LVEF, with the greatest benefits, especially for HF hospitalization, observed in patients with a LVEF below approximately 60%. Therapeutic benefits of sacubitril/valsartan with respect to HF hospitalization and cardiovascular death are robust among patients with HFrEF; the PARAGON-HF data suggest that this benefit could be extended to patients with EF not frankly reduced (LVEF ≤ 55-60%). The treatment effect across the EF continuum was also observed in the CHARM clinical program. As in PARAGON-HF, there was a potential benefit in favor of candesartan versus placebo in patients with an EF lower than 53%. 20 This effect was also observed in a TOPCAT post-hoc analysis. 21 Again, these data enhance the understanding of HFpEF but also raise questions about how we have been interpreting and diagnosing HF, and whether a broader range of patients (e.g., LVEF < 35%) could benefit from neurohormonal modulation. Despite this, there are no conclusive definitions onmid-range EF, where there probably be already disease progression and contractile impairment. The PARAGON-HF is part of the sacubitril/valsartan clinical development program and provide us with another piece in the puzzle of neprilisin/ RAS inhibition in the complex scenario of HF syndrome. The study includes the assessment of the safety and efficacy of sacubitril/valsartan in different scenarios of HF including recently decompensated patients, across the spectrum of HF ejection fraction, pediatric HF patients and Chagas cardiomyopathy. In addition, the PARALLAX-HF trial 22 will include patientswithaLVEF≥40%andcomplete theEFcontinuum analysis. Soon expected is the PARADISE-MI trial, 23 that will evaluate the safety and efficacy of sacubitril/valsartan versus ramipril in patients who have recently suffered a myocardial infarction. The study volunteers will not necessarily have a LVEF < 40%, as long as they have signs of pulmonary congestion requiring intravenous treatment with diuretics, vasodilators, vasopressors and/ or inotropes, during the index hospitalization. 23 These new trials will bring new perspectives and possible therapeuthic options for patients with cardiovascular diseases associated with high morbidity and mortality . Author contributions Conception and design of the research: JFK Saraiva. Writing of the manuscript: JFK Saraiva, Oliveira IBD. Potential Conflict of Interest José Francisco Saraivais investigator in clinical trials mentioned in the paper. Isadora de Oliveira is medical affairs role in a company that may direct or indirectly benefit from this publication. Sources of Funding There were no external funding sources for this study. Study Association This study is not associated with any thesis or dissertation work. Ethics approval and consent to participate This article does not contain any studies with human participants or animals performed by any of the authors.