Aims The current European Society of Cardiology guidelines provide clear indication for the treatment of acute and chronic heart failure (HF).Nevertheless,there is the constant need of real-world evidence concerning the effectiveness,adherence and persistence to drug therapy.We investigated the use of sacubitril/valsartan for the treatment of HF with reduced ejection fraction in real-world clinical practice in Italy.Methods An observational, retrospective,non-interventional cohort study based on electronic medical records from nine specialized hospital heart failure Centers in Italy was carried out on patients prescribed with sacubitril/valsartan.Results Overall,948 patients had a prescription of sacubitril/valsartan, 924 (mean age 64.5 years, 84.6% male) had 6 months of characterization and 12 months of follow-up. The initial dose was 24/26 mg for 548 (59.3%),49/51 mg for 333 (36.0%),97/103 mg for 43 (4.7).The final dose was available for 881 patients and it was:24/26 mg for 254 (28.8%),49/51 mg for 229 (26.0%),97/103 mgfor 398 (45.2).The time to maximal dose prescribed (weeks) was:for 97/103 mg 6.9 ± 6.2 weeks;for 49/51 mg 6.2 ± 6.7 weeks.Blood pressure and hypotension in 65% of the patients, and worsening of chronic kidney disease in 10.6% were the main reasons for not reaching target dose; fifty percent had a change in sacubitril/valsartan dose during follow-up and 70.2% patients were persistent with treatment during the last three months of follow-up, with a sensitivity analysis (persistence during the last four months of follow-up) showing 72.0% persistence. Adherence data, available for 387 patients, showed fully adherence for 53%.Discontinuation (102/387 patients) was mainly due to hypotension and occurred after a mean time of 34.3 ± 28.7 weeks. During follow-up, of the 606 patients with available data, 434 patients (71.6%) had an HF add-on drug or drugs concomitant to sacubitril/valsartan. Although not significantly (p=0.405), HF-related hospitalization during follow-up was higher in not persistent patients (23.9%) versus persistent (19%) to sacubitril/valsartan treatment.Pharmacoutilization data at 1-year expressed as medication possession ratio (MPR) are shown in the Figure.Conclusions Real-world data of sacubitril/valsartan use in clinical practice in Italy show a rapid titration of to target dose, high therapeutic adherence allowing a good level of therapeutic management in line with ESC guidelines in patients with reduced ejection fraction.