Mineralocorticoid receptor antagonist use in chronic heart failure: a real-world analysis focused on preserved ejection fraction and safety outcomes
M P Diaz, A Carmona, D Rico, N Montufar, N Mohamed, L Garcia, A Bustos, M Raya, F Gutierrez, F GomezAbstract
Background/Introduction
Mineralocorticoid receptor antagonists (MRAs) are the cornerstone of heart failure with reduced ejection fraction (HFrEF) therapy. Their role in heart failure with preserved ejection fraction (HFpEF) remains poorly defined and debated. This study describes the clinical profile and evolution of patients with chronic heart failure receiving SGLT2 inhibitor therapy, with or without concomitant MRA, with a focus on HFpEF.
Purpose
To analyze the clinical characteristics, treatment patterns, and short-term safety outcomes associated with MRA use in a real-world cohort of patients with chronic heart failure, stratified by left ventricular ejection fraction (LVEF).
Methods
A retrospective multicenter study was conducted. Consecutive patients with chronic heart failure who were followed up in heart failure units and on SGLT2 inhibitor therapy were included between 2023-2025. Patients were stratified into MRA and non-MRA users. Clinical, analytical, and outcome data at 3 and 6 months were analyzed. Contingency tables, Student's t-test, and multivariate logistic regression (expressed as odds ratios, OR) were used to identify factors associated with MRA use and to compare outcomes.
Results
Among the 168 patients treated with SGLT2 inhibitors, 98 (58.3%) received an MRA, while 70 (41.7%) did not. Within the MRA group, 55 (56.1%) patients had HFpEF and 43 (43.9%) had HFrEF (p=0.043 vs. non-MRA group). The clinical characteristics and comorbidities were well balanced between the groups. Multivariate analysis identified reduced LVEF (OR 1.9; p=0.045), normal/overweight BMI (OR 1.95; p=0.038), and concomitant treatment with ARNI (OR 21.23; p=0.024) and ACEi/ARB (OR 2.6; 95% CI 1.4-5.1; p<0.05) as factors independently associated with MRA prescription. No significant differences were observed in creatinine, glomerular filtration rate, or serum potassium levels at 3 and 6 months after treatment initiation. Regarding clinical outcomes, the only significant difference was a lower rate of emergency department visits at 3 months in the MRA group (p=0.022), with no differences in all-cause re-hospitalization or mortality.
Conclusion(s)
In this real-world cohort, MRA use was strongly associated with guideline-directed medical therapy for HFrEF, including ARNI. Importantly, in patients with HFpEF, MRA use was not associated with worsening renal function or hyperkalemia over 6 months, addressing a primary concern for its use. The need for higher diuretic doses in the non-MRA group suggests a potential unmet therapeutic requirement. Short-term clinical outcomes were similar, supporting the safety of MRAs in a contemporary heart failure population on SGLT2 inhibitors. Prospective studies with longer follow-up are needed to assess the impact on hard endpoints.Baseline Concomitant HF TreatmentsFor image description, please refer to the figure legend and surrounding text.