The implementation into clinical practice of new therapeutic strategies that Coll ld improve the prognosis of patients with heart failure (HF) with reduced ejection fraction (HFrEF) remains relevant. Innovative approach is to restore imbalances of neurohumoral systems by inhibiting angiotensin II receptor and neprilysin. The review presents the role of the natriuretic peptides system in the HFrEF pathophysiology, historical approaches to neurohormonal modulation, clinical pharmacology of the first in the class of angiotensin receptor and neprilysin inhibitor sakubitril/valsartan. The results of the study PARADIGM-HF, in which sakubitril/valsartan therapy in patients with HFrEF compared with the recommended doses of enalapril was associated with the decrease of the of cardiovascular death and hospitalizations for HF by 20%, the risk of death from any cause by 16%, improvement of symptoms and exercise tolerance. Sakubitril/valsartan tolerated better than enalapril, rarely causes a Coll gh, hyperkalemia or renal dysfunction. There was no increase in the risk of angioedema. Based on the results of the study PARADIGM-HF sakubitril/valsartan was included in the national and international guidelines for HF.