Modulação neuro-hormonal: o novo paradigma do tratamento farmacológico da Insuficiência Cardíaca

Translated title of the contribution: Neurohormonal modulation: The new paradigm of pharmacological treatment of heart failure

J. Silva-Cardoso, D. Brás, F. Canário-Almeida, A. Andrade, L. Oliveira, F. Pádua, C. Fonseca, N. Bragança, S. Carvalho, R. Soares, J. Ferreira Santos

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


The current paradigm of medical therapy for heart failure with reduced ejection fraction (HFrEF) is triple neurohormonal blockade with an angiotensin-converting enzyme inhibitor (ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA). However, three-year mortality remains over 30%. Stimulation of counter-regulatory systems in addition to neurohormonal blockade constitutes a new paradigm, termed neurohormonal modulation. Sacubitril/valsartan is the first element of this new strategy. PARADIGM-HF was the largest randomized clinical trial conducted in HFrEF. It included 8442 patients and compared the efficacy and safety of sacubitril/valsartan versus enalapril. The primary endpoint was the composite of cardiovascular mortality and hospitalization due to HF, which occurred in 914 (21.8%) patients receiving sacubitril/valsartan and in 1117 (26.5%) patients receiving enalapril (HR 0.8, 95% CI 0.73-0.87, p=0.0000002; NNT 21). Sacubitril/valsartan reduced both primary endpoint components, as well as sudden cardiac death, death due to worsening HF, and death from all causes. Patients on sacubitril/valsartan reported less frequent deterioration of HF and of quality of life, and discontinued study medication less frequently because of an adverse event. PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril, with a 20% greater impact on cardiovascular mortality compared to ACEIs. Accordingly, in 2016, the European (ESC) and American (ACC/AHA/HFSA) cardiology societies simultaneously issued a class I recommendation for the replacement of ACEIs by sacubitril/valsartan in patients resembling PARADIGM-HF trial participants.

Translated title of the contributionNeurohormonal modulation: The new paradigm of pharmacological treatment of heart failure
Original languagePortuguese
Pages (from-to)175-185
JournalRevista Portuguesa de Cardiologia
Issue number3
Publication statusPublished - Mar 2019


  • Angiotensin-receptor neprilysin inhibitor
  • Cardiovascular mortality
  • Heart failure with reduced ejection fraction
  • Hospitalization due to heart failure
  • Neurohormonal modulation
  • Sacubitril/valsartan


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