KEY POINTS:
- Finerenone, a non-steroidal mineralocorticoid (MRA), increased serum potassium levels more often than placebo. However, adverse events from hyperkalemia were rare
- The incidence of cardiovascular death or heart failure exacerbation was lower in patients using finerenone, even when serum potassium was elevated, as compared to use of the placebo group with a normal serum potassium
The FINEARTS-HF trial, published in September of 2024, demonstrated that finerenone, significantly reduced the risk of hospitalization or urgent outpatient visits in patients with HFpEF and HFmrEF. In this multi-center, randomized, double-blind, placebo-controlled trial 6,001 patients were randomized in a 1:1 fashion to receive finerenone or placebo.
Dosing for finerenone was 10mg for baseline GFR≤60 or 20mg for GFR≥60. Dose titration occurred at follow-up visits, with dose reductions advised if potassium levels exceeded 5.5mmol/L and discontinuation recommended for levels greater than 6mmol/L.
The study population had a mean age was 72 years and 46% were women. The mean LVEF was 53% and the majority had NYHA class II HF (69%).
As a follow up to this trial, researchers examined the prevalence of hyperkalemia and their connection to clinical outcomes in a study presented at the American Heart Association Scientific Sessions in November of 2024 with simultaneous publication in JAMA Network. This study investigated the prevalence of high and low serum potassium (>5.5mmmol/L or <3.5mmol/L respectively), the risk factors for deranged serum potassium, and clinical outcomes associated with these conditions.
Baseline potassium levels were similar between two groups, but at one-month potassium levels were 4.59mmol/L in the finerenone group vs 4.39mmol/L in the placebo group.
Those taking finerenone had an increased risk of high potassium compared to placebo (HR 2.16 [95%CI, 1.83-2.56]; P < .001) and a decreased risk for low potassium (HR, 0.46 [95% CI, 0.38-0.56]; P < .001). Risk factors for hyperkalemia, regardless of treatment status, included diabetes, male, diabetes, myocardial infarction, worse baseline kidney function, and higher baseline potassium levels.
Despite the increased risk hyperkalemia with finerenone, hyperkalemia prompting hospitalization was infrequent in both groups and no potassium-related deaths occurred in either group.
Patients with potassium levels above 5.5 mmol/L or below 3.5 mmol/L were linked to an increased risk of adverse clinical outcomes, regardless of treatment group. However, finerenone reduced the risk of worsening heart failure or cardiovascular death even in those with elevated potassium levels, as compared to those with normal potassium using placebo one month after randomization (HR,0.84 [95% CI, 0.55-1.30] vs 0.83 [95% CI, 0.74-0.92]; interaction P = .72).
In patients with heart failure with mildly reduced or preserved ejection fraction, finerenone resulted in more frequent hyperkalemia and less frequent hypokalemia. However, with protocol-directed surveillance and dose adjustment, clinical benefit associated with finerenone relative to placebo was maintained even in those whose potassium level increased to greater than 5.5 mmol/L.
- Docherty KF, Henderson AD, Jhund PS, et al. Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: A Prespecified Analysis of The FINEARTS-HF Trial. Circulation2024;Sep 29:[Epub ahead of print].
- Vardeny O, Vaduganathan M, Claggett BL, et al. Finerenone, Serum Potassium, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JAMA Cardiol.Published online November 17, 2024. doi:10.1001/jamacardio.2024.4539