The implementation of modern guideline-directed medical therapy among hospitalized patients with heart failure with reduced ejection fraction: real-world experience from two tertiary cardiac centers

Abstract Background According to the 2021 ESC HF Guidelines (GLs), the conventional triple therapy (TT) (RASi+βB+MRA) of HFrEF has been supplemented with the SGLT2 inhibitor dapa- and empagliflozin as the fourth pillar of the foundational quadruple therapy (QT) recommended for all HFrEF patients. Aim To assess the changes in the implementation of GDMT and investigate its impact on the prognosis among hospitalized HFrEF patients in light of the 2021 HF GLs. Patients and methods A retrospective data analysis of a consecutive cohort of HFrEF patients hospitalized due to HF between 01/01/2019 and 31/12/2023 at two tertiary cardiac centers was performed. Patients were classified into two groups: those hospitalized before and those after the publication of the 2021 ESC HF GLs (27/08/2021). Differences in the implementation of the drug therapy were analysed using the Chi-square test. 1-year all-cause mortality (ACM) was compared using Kaplan-Meier method and log-rank test. The independent predictors of the 1-year ACM were investigated with uni-, and multivariate Cox-regression analysis. Results A total cohort of 560 patients (male: 76%, age: 63 [51-72] years, coronary artery disease: 46%, diabetes: 38%, atrial fibrillation: 44%, LVEF: 25 [20-30]%, eGFR: 57 [43-74]mL/min/1.73m²; NT-proBNP: 5574 [2529-10960]pg/mL) was treated with a high proportion of TT (80%) and with QT (TT + SGLT2i) in 34% at discharge. After the publication of the 2021 ESC HF GLs, the proportion of patients on these SGTL2is improved (10% vs 57%, p<0.001; in the group before vs. after the publication of the GLs), resulting in an increased proportion of patients on QT (10% vs. 52%, p<0.001). There was no significant difference between groups regarding the use of TT (6% vs. 3%) or QT (1% vs. 3%) at target doses. The 1-year ACM was more favourable for those receiving QT (non-QT and non-TT: 41% vs. TT: 16% vs. QT: 11%, p<0.001). According to the multivariate Cox-regression analysis, older age, and more advanced left ventricular systolic dysfunction proved to be negative independent predictors of 1-year ACM, while "de novo" diagnosis of HFrEF and the application of TT/QT (adjusted HR: 0.303, 95% CI: 0.207-0.445, p<0.001) resulted in better outcomes. Conclusions The 2021 ESC HF GLs have led to a breakthrough regarding the modern drug treatment recommended for all patients in HFrEF. Our results demonstrated that the introduction of SGLT2is and the use of QT was feasible even in the everyday practice among complex, multimorbid HFrEF patients requiring hospitalization and the implementation of TT/QT was accompanied by a better prognosis.