[Position paper of the Italian Society of Cardiology: The renin-angiotensin-aldosterone system (RAAS) blockade in heart failure patients - Part I: From RAAS identification to clinical trials]

Renin-angiotensin-aldosterone (RAAS) system inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction and has been implemented by the introduction of angiotensin receptor-neprilysin inhibitors (ARNI), that combine RAAS inhibition with the inhibition of neprilysin, enhancing the favorable effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a favorable effect of sacubitril/valsartan over enalapril in terms of mortality and heart failure hospitalization rate reduction. Then several randomized clinical trials and observational studies confirmed the favorable role of ARNI in different clinical scenarios, supporting the guideline class I recommendation for the use of sacubitril/valsartan in patients with reduced systolic function. The first part of this position paper summarizes the history of RAAS inhibition and reports the results of ARNI trials that support the recommendations of the most recent guidelines.