The effect of kidney function on the optimization of medical therapy and on mortality in heart failure with reduced ejection fraction

Introduction: Renal dysfunction is a main limiting factor of applying and up-titrating guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction (HFrEF).Objective: Our retrospective monocentric observational study aimed to analyse the application ratio of combined neurohormonal antagonist therapy (RASi: ACEI/ARB/ARNI + 8B + MRA) and 12-month all-cause mortality differences in terms of renal dysfunction among HFrEF patients hospitalized for heart failure.Method: We retrospectively analysed the cohort of consecutive HFrEF patients, hospitalized at the Heart Failure Unit of our tertiary cardiological centre in 2019-2021. The application ratio of discharge triple therapy (TT) in five groups established on admission eGFR parameters, representing severity of renal dysfunction (eGFR >= 90, eGFR = 60-89, eGFR = 45-59, eGFR = 30-44, eGFR<30 ml/min/1.73 m(2)) was investigated with chi-square test, while 12-month mortality differences were analysed with Kaplan-Meier method and log-rank test.Results: 257 patients were included. Median eGFR was 57 (39-75) ml/min/1.73 m(2), 54% of patients had eGFR<60 ml/min/1.73 m(2). The proportion of patients in eGFR >= 90, 60-89, 45-59, 30-44, <30 ml/min/1.73 m(2) subgroups was 12%, 34%, 18%, 21%, 15%, respectively. 2% of patients were on dialysis. Even though the application rate of TT was notably high (77%) in the total cohort, more severe renal dysfunction led to a significantly lower implementation rate of TT (94%, 86%, 91%, 70%, 34%; p<0.0001): the application rate of RASi (100%, 98%, 96%, 89%, 50%, p<0.0001), 8B (94%, 88%, 96%, 79%, 68%; p = 0.003) and MRA therapy (97%, 99%, 98%, 94%, 82%; p = 0.001) differed significantly. 12-month all-cause mortality was 23% in the whole cohort. Mortality rates were higher in more severe renal dysfunction (3%, 15%, 22%, 31%, 46%; p<0.0001).Conclusion: Even though the proportion of patients on TT in the whole cohort was remarkably high, renal dysfunction led to a significantly lower application ratio of TT, associating with worse survival. Our results highlight that despite renal dysfunction the application of HFrEF cornerstone pharmacotherapy is essential.