The Impact of Introducing Sacubitril/Valsartan and SGLT2 Inhibitors in a Cohort of Patients with Reduced-Ejection-Fraction Heart Failure: A Real-Life Observational Study

<b>Background/Objectives</b>: Reduced-ejection-fraction heart failure (HFrEF) constitutes a challenge due to its high morbidity and mortality. The use of sacubitril/valsartan (angiotensin receptor-neprilysin inhibitors [ARNI]) and SGLT2 inhibitors (SGLT2i) represents a change in management approach with a demonstrated association with positive ventricular remodeling and a reduction in cardiovascular events. We describe the clinical and therapeutic course of patients with HFrEF in a specialized unit, comparing two consecutive periods (2011-2016 vs. 2017-2021), with emphasis on the impact of ARNI and SGLT2i upon clinical parameters and the use of devices. <b>Methods</b>: A retrospective, longitudinal observational study was carried out in 1363 outpatients with HFrEF, with at least two years of follow-up. Clinical characteristics, treatments, the evolution of left ventricular ejection fraction (LVEF), mortality, and the use of devices (implantable cardioverter-defibrillator [ICD], cardiac resynchronization therapy [CRT]) were evaluated. <b>Results</b>: A total of 1363 patients were analyzed, showing a significant therapeutic change in the 2017-2021 group with the incorporation of ARNI (40%) and SGLT2i (25%). This cohort achieved better ventricular recovery, with a significantly higher mean LVEF at one year compared to the 2011-2016 group (44.3% vs. 42.1%; <i>p</i> = 0.004). Regarding devices, ICD implantation rate decreased in the recent period (7.2% vs. 11.1%; <i>p</i> = 0.016), while CRT indication increased. Most importantly, all-cause mortality after two years fell from 9.4% to 5.9% (<i>p</i> = 0.023). Multivariate analysis confirmed that this survival improvement was independently associated with the study period (HR 1.57 for the earlier group) and was linked to the protective effect of contemporary pharmacological treatments. <b>Conclusions</b>: The systematic introduction of ARNI and SGLT2i in the treatment of HFrEF was associated with improved ventricular function, reduced need for device implantation, and lower mortality over the middle term in a real-life clinical setting.