Abstract Body (Do not enter title and authors here): Background: Finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of cardiovascular death and total worsening heart failure (HF) events in patients with HF with mildly reduced or preserved ejection fraction in FINEARTS-HF. We investigated the frequency and predictors of hyperkalemia, and examined the treatment effect of finerenone, relative to placebo, on clinical outcomes based on post-randomization potassium levels.

Methods: FINEARTS-HF was a multicenter, randomized, double-blind trial comparing finerenone (titrated to 20 or 40mg, depending on baseline kidney function) versus placebo in patients with HF with LVEF ≥40%, structural heart disease, and elevated natriuretic peptide levels. Per protocol, investigators down-titrated or temporarily interrupted study medication if potassium levels were ≥5.5mmol/l. The primary endpoint was the composite of total worsening HF events and cardiovascular death. Landmark analyses were conducted to examine risks of the primary endpoint subsequent to 1-month measurements of potassium levels separately in each treatment arm.

Results: Among 6,001 randomized participants, mean baseline potassium levels were 4.4±0.5mmol/l. At 1 month, the effect of finerenone on potassium was +0.19 (0.17-0.21) mmol/l, a difference that persisted during the trial (Figure 1). Regardless of treatment assignment, patients who developed any potassium level >5.5mmol/l in follow-up were more likely to be men, with histories of diabetes and recent worsening HF events, worse baseline kidney function and higher baseline potassium levels. Finerenone increased the risks of any potassium level >5.5mmol/l (14.3% vs. 6.9%), and decreased the risks for hypokalemia (4.4% vs. 9.7%). Hyperkalemia-related hospitalizations were infrequent, and there were no hyperkalemia-related deaths in either arm (Figure 2). During a median follow-up of 2.6 years, a U-shaped association was observed between potassium levels measured after 1 month of treatment and subsequent risks of the primary outcome, such that for any given level of potassium, risks were generally lower in patients treated with finerenone compared to patients treated with placebo (Figure 3).

Conclusions: In patients with HFmrEF/HFpEF, finerenone resulted in early modest increases in potassium levels. However, the clinical benefit of finerenone was maintained even in the setting of moderate hyperkalemia.