Association of in-hospital mineralocorticoid receptor antagonist initiation with outcomes according to guideline-defined eGFR and potassium eligibility in patients with heart failure

BACKGROUND Evidence on the use of mineralocorticoid receptor antagonists (MRAs) in patients hospitalized for heart failure (HF) with concomitant advanced chronic kidney disease or hyperkalemia remains limited. We evaluated whether the association between in-hospital MRA initiation and outcomes differed according to eligibility defined by estimated glomerular filtration rate (eGFR) and serum potassium levels. METHODS This was a sub-analysis of JROADHF-NEXT, a prospective, nationwide, multicenter registry of patients hospitalized for HF in Japan between February 2019 and June 2021. This study included patients who were MRA-naive at admission. Those with an admission eGFR ≤30 mL/min/1.73 m2 or serum potassium ≥5.0 mmol/L were classified as ineligible; those with eGFR >30 mL/min/1.73 m2 and serum potassium <5.0 mmol/L were classified as eligible. Clinical outcomes were compared according to in-hospital MRA initiation within each eligibility group. The primary endpoint was a composite of cardiovascular death or hospitalization for HF within 2 years after discharge. RESULTS Among 2792 patients (mean age 73 ± 14 years; 61% male), 1332 (48%) initiated MRAs during hospitalization, and 751 (27%) were classified as ineligible. Over a median follow-up of 731 days, the primary endpoint of cardiovascular death or HF hospitalization occurred in 684 patients (24.5%). In Cox proportional hazards analysis, in-hospital MRA initiation was associated with a lower risk of the primary endpoint [adjusted hazard ratio (aHR), 0.75; 95% confidence interval (CI), 0.64-0.88; p < 0.001]. No statistically significant interaction was observed according to MRA eligibility (ineligible: aHR, 0.70; 95% CI, 0.52-0.93; eligible: aHR, 0.83; 95% CI, 0.68-1.01; p for interaction = 0.326). CONCLUSIONS In this nationwide real-world cohort, in-hospital MRA initiation was associated with a lower 2-year risk of the primary endpoint, and no statistically significant interaction was detected according to eGFR- and potassium-based eligibility. These hypothesis-generating findings warrant prospective evaluation with systematic safety monitoring.