Understanding Hyperkalemia Risk, Effect on Benefits with Finerenone, with Orly Vardeny, PharmD, MS

An analysis of the FINEARTS-HF trial sheds further light on the impact and prevalence of hyperkalemia among patients with heart failure and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) receiving finerenone (Kerendia).

Presented at the American Heart Association (AHA) Annual Scientific Sessions 2024, the study suggests hospitalizations for hyperkalemia were infrequent and patients receiving finerenone experienced clinical benefit even in the presence of moderate hyperkalemia.

“I think something that often deters clinicians from using MRAs is if potassium bumps a little bit above 5, maybe even close to 5.5 mmol/l and then the question is, ‘Oh, should I stop the medication? Is the benefit still maintained? Am I causing harm?’,” explained principal investigator Orly Vardeny, PharmD, MS, associate professor of medicine at the Minneapolis VA Health Care System and University of Minnesota, in an interview with HCPLive Cardiology. “So, I think that concern has dissuaded a lot of clinicians from using these, which are lifesaving therapies in HFrEF, in these patients [with HFpEF].”

FINEARTS-HF, which was originally presented at ESC Congress 2024, was a global, randomized, placebo-controlled clinical trial of finerenone among patients diagnosed with New York Heart Association class II-IV heart failure, an LVEF of 40% or greater, and receiving diuretic treatment for at least 30 days prior to randomization. The trial randomized 2998 and 3003 patients to placebo and finerenone, respectively, and followed them for a primary composite endpoint of cardiovascular death and total heart failure events.

In the overall trial, use of finerenone was associated with a statistically significant 16% relative reduction in rate of primary outcome events compared with placebo therapy (rate ratio [RR], 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = .007).

Per trial protocol, patients who experienced potassium levels of 5.5 mmol/l or greater were downtitrated or had medication temporarily stopped. In the study at AHA 2024, Vardeny and colleagues sought to examine risks of the primary endpoint subsequent to 1-month measurements of potassium levels separately in each treatment arm.

Among the 6001-patient cohort included in FINEARTS-HF, the mean baseline potassium levels were 4.4 (SD, 0.5) mmol/l. At 1 month, use of finerenone was associated with a 0.19 (0.17-0.21) mmol/l increase in potassium levels, which investigators noted was an effect that persisted for the duration of the trial. Investigators also highlighted patients who developed any potassium level greater than 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, regardless of treatment assignment.

Further analysis suggested use of finerenone was associated with an increased risks of any potassium level exceeding 5.5 mmol/l (14.3% vs. 6.9%) and a decreased risk for hypokalemia (4.4% vs 9.7%). This analysis also revealed hyperkalemia-related hospitalizations during the trial were infrequent and there were no hyperkalemia-related deaths in either arm.

Investigators also called attention to results demonstrating a U-shaped association between potassium levels measured after 1 month of treatment and subsequent risks of the primary outcome, with results indicating, for any given level of potassium, risks were lower in patients treated with finerenone compared to patients treated with placebo therapy.

For more on this study, the incidence of hyperkalemia in patients receiving finerenone, and more, check out interview with Vardeny from AHA 2024.

Relevant disclosures for Vardeny include Cardior, Bayer, Moderna, and Cardurion.

References:

1. Vardeny O, Vaduganathan M, Clagget B, et al. Finerenone and Risk of Hyperkalemia in Patients with Heart failure with Mildly Reduced or Preserved Ejection Fraction. Paper presented at: American Heart Association Scientific Sessions 2024; November 15 - 18; Chicago, Il. Accessed November 16, 2024.
2. Solomon SD, McMurray JJV, Vaduganathan M, et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2024;391(16):1475-1485. doi:10.1056/NEJMoa2407107