The role of sacubitril/valsartan in the treatment of chronic heart failure with reduced ejection fraction in hypertensive patients with comorbidities: From clinical trials to real-world settings

Abstract Background Sacubitril/valsartan, the first agent to be approved in a new class of drugs called angiotensin receptor neprilysin inhibitors (ARNIs), has been shown to reduce cardiovascular mortality and morbidity compared to enalapril in outpatient subjects with chronic heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, there is little real-world evidence about the efficacy of ARNIs in elderly hypertensive patients with HFrEF and comorbidities. Methods In this prospective open-label study, 108 subjects, 54 of them (mean age 78.6 ± 8.2 years, 75.0 % male), with HFrEF (29.8 ± 4.3 %) and New York Heart Association (NYHA) class II-III symptoms were assigned to receive ARNIs twice daily, according to the recommended dosage of 24/26, 49/51, 97/103 mg. Patients were gender- and age-matched with a control arm of patients with HFrEF receiving the optimal standard therapy for HF. The clinic blood pressure (BP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), blood glucose and glycated hemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 12 months. During the follow-up, the clinical outcomes, including mortality and re-hospitalization for HF, were collected. Results NYHA class significantly improved in the ARNI arm compared to the control (24.9 vs. 6.4 %, shifting from class III to II, and 55.4 vs. 25.2 %, from class II to I, p  Conclusions In elderly patients with HFrEF and comorbidities, ARNI treatment seems effective and safe. The improvement in LVEF and cardiac remodeling, BP, eGFR, serum glucose, UA and HbA1c could be the mechanisms by which ARNIs play their beneficial role on clinical outcomes. However, these results need to be confirmed in studies involving a greater number of subjects, and with a longer follow-up.