Renin-angiotensin-aldosterone system inhibition in patients affected by heart failure: efficacy, mechanistic effects and practical use of sacubitril/valsartan. Position Paper of the Italian Society of Cardiology

Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the positive effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clinical trials and observational studies investigated its role in different clinical settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients' clinical profile is relevant to implement the use of ARNI in the clinical practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiology on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community.