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.

Pharmacoutilization and adherence to sacubitril/valsartan in real world: the REAL.IT study in HFrEF

“…A total of 924 patients were included in the overall REAL.IT study. 7 Their demographic (mean age 65 years, 85% male) and clinical characteristics were in line with other international studies involving patients with sacubitril/valsartan (mean age similar to that of patients enrolled in the PARADIGM-HF study 8 and slightly lower than the mean age of patients enrolled in real-world utilization studies on sacubitril/valsartan). 9…”

“…The main results of the study have been already published. 7 The study population comprised ambulatory patients with a diagnosis of HFrEF attending outpatient clinics for HF management at the nine centres and who were prescribed sacubitril/valsartan from 01 October 2016 (the launching year in Italy) to 30 June 2019 (defined as the inclusion period). The index date was defined as the date of the first prescription of sacubitril/valsartan during the inclusion period, while during the 6 months before the index date (i.e.…”

“…Patients with no information on age or sex were not included in the analysis. 7 The data for the retrospective analysis were retrieved from the EMR and administrative regional health databases of the centres, which incorporated records of the personal health, health examination, and hospital visit of patients.…”

“…Consequently, a multicentre, retrospective, cohort study starting from data from Italian outpatient specialist clinics was carried out and recently reported. 7 In this paper, we present the results of the pharmacoutilization analysis of patients treated with sacubitril/valsartan in our real-world study in HFrEF.…”

“…Therefore, there is a need for observational studies analysing sacubitril/valsartan use in the real world of daily clinical practice in Italy, given the indications of both Italian regulatory rules and the guideline‐directed medical therapy for HF. Consequently, a multicentre, retrospective, cohort study starting from data from Italian outpatient specialist clinics was carried out and recently reported 7 …”