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Il trattamento con sacubitril/valsartan ha assunto un ruolo di primo piano nelle ultime linee guida sia europee che americane, ed è attualmente raccomandato in classe I per il trattamento dei pazienti con ridotta frazione di eiezione. Accanto ai ben noti effetti sulla mortalità, sacubitril/valsartan agisce positivamente sulla riduzione dei valori di NT-proBNP e su parametri di rimodellamento ventricolare sinistro, determinando un rimodellamento inverso riconosciuto come uno degli effetti meccanicistici del farmaco atto a spiegare in parte il suo effetto favorevole sulla prognosi. Un’attenta valutazione del profilo di ogni singolo paziente consente un utilizzo più mirato e meglio tollerato del farmaco, garantendo anche in ambito di insufficienza cardiaca la strada della medicina di precisione. La seconda parte di questo position paper esplora gli effetti meccanicistici degli inibitori del recettore dell’angiotensina e della neprilisina e il loro posizionamento nelle linee guida, proponendo in ultima analisi un uso di sacubitril/valsartan in specifici contesti clinici. 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.

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.

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.