Interplay of serum potassium and kidney function with finerenone in heart failure with mildly reduced or preserved ejection fraction: Findings from FINEARTS-HF.

Abstract

AIMS Finerenone improved heart failure (HF) outcomes in patients with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). Clinical decision-making around initiation of mineralocorticoid receptor antagonists often relies on measures of kidney function and serum potassium (K+) levels. The aim of this study was to evaluate the efficacy and safety of finerenone across categories of serum K+ and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS Four mutually exclusive categories were created: (1) K+ ≤4.5 mmol/L and eGFR ≥60 ml/min/1.73 m2; (2) K+ >4.5 mmol/L and eGFR ≥60 ml/min/1.73 m2; (3) K+ ≤4.5 mmol/L and eGFR <60 ml/min/1.73 m2; and (4) K+ >4.5 mmol/L and eGFR <60 ml/min/1.73 m2. Outcomes and treatment effects were compared across these categories. The primary outcome was a composite of total HF events and cardiovascular death. The median follow-up was 32 months. A total of 6001 patients were included. Compared to patients with K+ ≤4.5 mmol/L and eGFR ≥60 ml/min/1.73 m2, those with eGFR <60 ml/min/1.73 m2, irrespective of K+ levels, had a 1.5- to 2-fold higher risk of experiencing primary outcome and fatal events across treatment groups. No significant interaction was observed on the effects of finerenone (vs. placebo) on the primary outcome across K+/eGFR categories. The respective risk ratios (RR) and 95% confidence intervals (CI) were: (1) K+ ≤4.5 mmol/L and eGFR ≥60 ml/min/1.73 m2: RR 0.66, 95% CI 0.52-0.85; (2) K+ >4.5 mmol/L and eGFR ≥60 ml/min/1.73 m2: RR 0.92, 95% CI 0.65-1.30; (3) K+ ≤4.5 mmol/L and eGFR <60 ml/min/1.73 m2: RR 0.91, 95% CI 0.74-1.13; (4) K+ >4.5 mmol/L and eGFR <60 ml/min/1.73 m2: RR 0.92, 95% CI 0.72-1.17; p for interaction = 0.20. Patients with low eGFR and/or high K+ experienced more frequent adverse events and treatment discontinuation; still, categories of K+/eGFR did not significantly modify the relative risk of adverse events with finerenone versus placebo (p for interaction > 0.1 for all adverse events). CONCLUSIONS No significant heterogeneity was found on the effect of finerenone to reduce primary outcome events. Still, adverse events and treatment discontinuation were more frequent among patients with low eGFR and/or high K+, suggesting. that such patients may require tailored strategies to mitigate adverse events and avoid treatment discontinuation.