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

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.