Steroidal vs. non-steroidal mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction: a propensity-matched multi-network nationwide cohort study

AIMS: Heart failure (HF) continues to portend significant morbidity and mortality within the USA. Data regarding the efficacy of mineralocorticoid receptor antagonists (MRAs) in HF with preserved ejection fraction (HFpEF) remains unclear. Finerenone, a non-steroidal MRA, has demonstrated reduction in hospitalizations in this population. However, the comparative efficacy of different MRA classes in these patients remains elusive. METHODS AND RESULTS: We conducted a retrospective observational cohort study using the TriNetX research network. We applied 1:1 propensity score matching (PSM) to compare patients with HFpEF initiated on finerenone vs. spironolactone. We examined 1-year risks of HF exacerbation, acute kidney injury (AKI), electrolyte derangements, and cardiovascular outcomes. We identified 254,417 patients with HFpEF and MRA use. After PSM, each cohort contained 491 patients. Analysis revealed that finerenone use was associated with a significantly lower risk of HF exacerbation (hazard ratio [HR] = 0.63 [95% confidence interval [CI]: 0.54, 0.74], P < 0.001), all-cause mortality (HR = 0.38 [95% CI: 0.23, 0.64], P < 0.001), and hypokalaemia (HR = 0.58 [95% CI: 0.40, 0.85], P = 0.001). The aforementioned results, along with a reduction in AKI risk, were statistically significant after stratified subgroup analysis by diabetes mellitus and chronic kidney disease. CONCLUSION: In this large real-world HFpEF cohort, finerenone use was associated with lower risks of HF exacerbation and all-cause mortality compared with spironolactone. These observational findings are hypothesis-generating and warrant confirmation in randomized trials.