[Position paper of the Italian Society of Cardiology: The renin-angiotensin-aldosterone system blockade in heart failure patients - Part II: Mechanistic effects of sacubitril/valsartan, placement in current guidelines and use in clinical practice].

The use of sacubitril/valsartan has been fully recognized in the most recent European and American guidelines that recommend in class I the prescription of this drug in heart failure patients with reduced systolic function. Besides the effects on cardiovascular mortality and heart failure hospitalization, sacubitril/valsartan significantly reduces NT-proBNP levels and improves cardiac remodeling, recognized as one of the mechanistic effects of the drug that is linked to favorable prognostic effects. A careful evaluation of the patients' clinical profile is needed to implement the use of sacubitril/valsartan into clinical practice and to make the treatment successful. This second part of the position paper focuses on the mechanistic effects of angiotensin receptor-neprilysin inhibitors and on its placement in current guidelines, also suggesting the use of sacubitril/valsartan in specific clinical settings.