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G Ital Cardiol (Rome). 2018 Oct;19(10):568-590. doi: 10.1714/2978.29843.

[ANMCO position paper on sacubitril/valsartan in the management of patients with heart failure].

[Article in Italian]

Author information

U.O. Cardiologia, Ospedale ASST, Cremona.
S.C. Centro Cardiovascolare, Azienda Sanitaria Universitaria Integrata, Trieste.
U.O. Cardiologia, Ospedale Civile "Augusto Murri", Fermo.
Polo Scienze Cardiovascolari e Toraciche, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "Agostino Gemelli", Roma.
Istituto di Fisiologia Clinica del CNR, Dipartimento Cardiotoracovascolare, ASST Grande Ospedale Metropolitano Niguarda, Milano.
De Gasperis Cardio Center, ASST Grande Ospedale Metropolitano Niguarda, Milano.
U.O.C. Cardiologia Universitaria, Dipartimento Cardiotoracico, AOU Policlinico Consorziale, Bari.
Dipartimento di Cardiologia, Policlinico di Monza, Monza (MB).
Cardiologia-UTIC, Ospedale Città di Castello (PG), USL Umbria 1.
S.C. Cardiologia, Ospedale Santo Spirito, Casale Monferrato (AL).
Dipartimento di Medicina Interna, Università degli Studi, Ospedale Policlinico San Martino, Genova.
Cardiologia Interventistica-UTIC, A.O. "G. Rummo", Benevento.
Unità Complessa di Cardiologia 1, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, Bergamo.
U.O.C. Cardiologia, Ospedale Bellaria, Bologna.
U.O.C. Cardiologia, Ospedale Garibaldi-Nesima, Azienda di Rilievo Nazionale e Alta Specializzazione "Garibaldi", Catania.


Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is the first medication to demonstrate a mortality benefit in patients with chronic heart failure and reduced ejection fraction (HFrEF) since the early 2000s. Sacubitril/valsartan simultaneously suppresses renin-angiotensin-aldosterone system activation through blockade of angiotensin II type 1 receptors and enhances the activity of vasoactive peptides including natriuretic peptides, through inhibition of neprilysin, the enzyme responsible for their degradation. In the landmark PARADIGM-HF trial, patients with HFrEF treated with sacubitril/valsartan had a 20% reduction in the primary composite endpoint of cardiovascular death or heart failure hospitalization, a 20% lower risk of cardiovascular death, a 21% to 20% lower risk of a first heart failure hospitalization, and a 16% to 20% lower risk of death from any cause, compared with subjects allocated to enalapril (all p<0.001).Following the trial, new international guidelines endorsed sacubitril/valsartan as a class I recommendation for the management of patients with HFrEF who remain symptomatic despite optimal medical management. In Italy, sacubitril/valsartan is reimbursed by the National Health Service since March 2017 within criteria set by the Italian Medicines Agency subject to patient inclusion in a dedicated monitoring registry. Although numerous post-hoc analyses of the original trial suggested that the benefits of this innovative medication may extend across a variety of subgroups, many questions do not yet have an evidence-based answer.In this position paper, we discuss the current role of sacubitril/valsartan in the management of chronic HFrEF, treatment eligibility and the modulating role of patients' characteristics. Moreover, we address concerns elicited by the PARADIGM-HF study and shortcomings of this novel drug, to clarify the place of this new therapy in the context of global care of heart failure in Italy. Our aim is to provide clinical cardiologists with a concise and practical guidance on when and how to use sacubitril/valsartan, to assist clinicians in closing the gap between scientific innovation and real-world experience.


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