Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction: Real-World Experience from Italy (the REAL.IT Study)

Abstract

Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study aimed to characterize the demographics, pharmacotherapy, clinical characteristics and outcomes of sacubitril/valsartan-treated Italian patients with HFrEF. Electronic medical records of patients initiating sacubitril/valsartan from October 2016 to June 2019 at nine specialized hospital outpatient HF centers across Italy were reviewed. Overall, 924 adults (mean age 64.5 years, 84.6% male) were included. At baseline, 38.7% had an ischemic HF etiology, 45.9% hypertension, 23.2% atrial fibrillation, 25.4% diabetes mellitus, 26.1% an implantable cardioverter-defibrillator and 31.9% coronary artery bypass grafting. There were no clear patterns of patient selection over time. During follow-up, NYHA class improved in 37.5% of patients after a mean of 5.3 ± 3.8 months; 36.1% and 16.7% of patients were in NYHA class III during characterization and after one year of follow-up, respectively. Left ventricular ejection fraction (LVEF) improved ≥5% in 56.3% of patients at one year; 39.7% had ≥30% reduction of N-terminal pro-B-type natriuretic peptide; 2.2% had hyperkalemia during characterization and 2.6% during follow-up; and 3.8% had hypotension during characterization and 12% during follow-up. A total of 50 (5.8%) of patients had device implantation (ICD/CRT) during follow-up. HF-related hospitalization was recorded in 19.6% of patients during follow-up; 3.8% of patients died, approximately 1.3% from cardiovascular causes. Our real-world data confirm the favorable effectiveness and tolerability of sacubitril/valsartan observed in pivotal randomized controlled trials.

Keywords: NYHA functional class; angiotensin receptor-neprilysin inhibitor; heart failure with reduced ejection fraction; real-world practice; sacubitril/valsartan.

Figure 1

Study design. The study period was between 1 April 2016 and 30 June 2020, and the inclusion period was between 1 October 2016 and 30 June 2019. There was a characterization period of 6 months before the index date (the date of the first prescription of sacubitril/valsartan), and all patients were followed up for at least 12 months from the index date to June 2020.

Figure 2

Flow chart of the study. * Patients with missing age or sex data and/or who did not have 6 months of characterization period and at least 12 months of follow-up available were excluded.