Finerenone Demonstrates Safety and Efficacy in Heart Failure When Combined With Diuretics

Finerenone (Kerendia; Bayer), a mineralocorticoid receptor antagonist (MRA), when used in tandem with loop and/or nonloop diuretics, saw a reduction in total heart failure events and cardiovascular deaths in a study published by JAMA Cardiology.1

Researchers performed a secondary analysis of results from the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF; NCT04435626), which was designed to assess the safety and efficacy of finerenone in patients with heart failure and mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF). The nonsteroidal MRA finerenone, like other MRAs, is designed to act as a potassium-sparing diuretic, which helps the body reduce sodium absorption without increasing potassium excretion.

A new clinical drug trial tests the efficacy and safety of finerenone, used to help reduce potassium expulsion for people on diuretics. | Image Credit: AdobeStock_ PhotobyTawat.jpeg

Diuretic therapies for treating heart failure are commonly used, but they can often have undesirable effects, especially with higher diuretic doses, which have been linked to worse outcomes—although the higher diuretic dose is a marker of heart failure severity.2 Higher doses of overdiuresis can lead to more severe conditions like kidney dysfunction or significant loss of body fluids like blood and water (hypovolemia).

In this analysis of data from the FINEARTS-HF trial, the primary and secondary outcomes observed were a composite of total heart failure (HF) events, unplanned HF hospitalization, and cardiovascular (CV) death.1 Outcomes were compared between finerenone and placebo based on whether patients were taking a nonloop diuretic, a loop diuretic, or both loop and nonloop diuretics at baseline.

Inclusion criteria were New York Heart Association (NYHA) class 2 through 5, diuretic use within 30 days of randomization within the trial, a left ventricular ejection fraction (LVEF) of 40% or higher with evidence of structural heart disease, and an elevated natriuretic peptide level. There were 5438 analyzable patients in the trial, 45.9% of whom were female, with a mean age of 72.1 (9.6) years.

For patients on loop diuretics, the daily dose was standardized using furosemide-equivalent dosing. At baseline, the patients were categorized into 4 diuretic categories: only nonloop diuretic, only loop diuretic at a furosemide-equivalent dose of 40 mg or less per day or more than 40 mg per day, and both loop and nonloop diuretics. Of the 5438 patients, 684 (12.6%) were taking nonloop diuretics, 3040 (55.9%) were taking 40 mg or less of furosemide-equivalent loop diuretic, 1145 (21.1%) were taking more than 40 mg of a loop diuretic, and 569 (10.5%) were taking both nonloop and loop diuretics. When establishing standard doses, the nonloop diuretics group was comprised of patients only receiving thiazide or thiazide-like diuretics.

A notable observation among patients on loop diuretics receiving more than 40 mg of a furosemide-equivalent dose was that they were older, had a longer history of HF hospitalization, had a higher NYHA class, and had a lower LVEF level than other groups. On the other hand, patients receiving only nonloop diuretics had a more favorable clinical profile, and those taking a nonloop diuretic, whether alone or in combination, more often had a history of hypertension. The incidence rate of the primary outcome was lowest in patients receiving only a nonloop diuretic and highest in those receiving more than 40 mg of furosemide-equivalent loop diuretic.

The benefit of finerenone compared with placebo did not differ among patients receiving the nonloop diuretic alone, the loop diuretic alone, or both. Regarding tolerability and safety, the placebo group showed that hypotension, elevated creatine, and hypokalemia (low blood potassium levels) were more common in patients receiving more than 40 mg of furosemide-equivalent loop diuretic when compared with patients in the other diuretic categories. While finerenone reduced the risk of hypokalemia, it increased the incidence of hypotension and hypokalemia; this was consistent across all the diuretic groups.

The tolerability and safety of finerenone were consistent regardless of increases or decreases in dosage of loop diuretics after randomization. Additionally, while the majority of patients did not have a dose change in loop diuretics, those randomized to finerenone were less likely to experience a dose increase compared with placebo (6 months: 7.4% vs 9.5%; P = .007; 12 months: 10.0% vs 13.9%; P < .001; 18 months: 12.0% vs 16.6%; P < .001) and more likely to experience a dose decrease or discontinuation (6 months: 15.0% vs 9.3%; P < .001; 12 months: 18.0% vs 11.6%; P < .001; 18 months: 19.9% vs 13.6%; P < .001).

“While the effect of finerenone might appear larger in patients receiving only nonloop diuretics and both loop and nonloop diuretics, these subgroups were relatively small, with few events, and the wide confidence intervals around the point estimates highlight the limited statistical power within these groups,” the study authors explained.

The study limitations included the unavailability of some furosemide-equivalent loop diuretic doses in a small number of patients. Diuretic efficacy, like urine output, was also unavailable. Changes in loop diuretic doses were only assessed at certain points and did not account for potential fluctuations between intervals.

“Compared to placebo, finerenone did not significantly reduce the initiation of a loop diuretic in patients not taking loop diuretics at baseline; however, finerenone reduced the need for loop diuretic dose intensification and led to a decrease in the mean loop diuretic dose,” the study authors noted. “Initiating finerenone therapy may facilitate a reduction in loop diuretic requirements.”

References

1. Chimura M, Jhund PS, Henderson AD, Yang M, Claggett BL, Desai AS, et al. Efficacy and tolerability of finerenone according to the use and dosage of diuretics: a prespecified analysis of the FINEARTS-HF randomized clinical trial. JAMA Cardiol. Published online August 13, 2025. doi:10.1001/jamacardio.2025.2551

2. Eshaghian S, Horwich TB, Fonarow GC. Relation of loop diuretic dose to mortality in advanced heart failure. Am J Cardiol. 2006;97(12):1759-1764. doi:10.1016/j.amjcard.2005.12.072