Limited Kidney Benefits With Finerenone in Heart Failure

SAN DIEGO — In patients with heart failure, treatment with finerenone provides some benefits in reducing the risk for macroalbuminuria. However, no significant changes are observed in estimated glomerular filtration rate (eGFR)-based kidney outcomes, an analysis of the recently published FINEARTS-HF trial shows.

“Among patients with heart failure with mildly reduced or preserved ejection fraction in the FINEARTS-HF, who were at relatively low risk of adverse kidney events, finerenone did not alter the frequency of a prespecified kidney composite outcome,” said first author Finnian R. McCausland, MB BCh, of Brigham and Women’s Hospital in Boston, Massachusetts, in presenting the findings at a press briefing for the American Society of Nephrology (ASN) Kidney Week 2024.

The analysis was published simultaneously in the Journal of the American College of Cardiology.

“Finerenone caused an initial expected decline in estimated glomerular filtration rate (eGFR), but did not alter the longer-term eGFR trajectory, compared with placebo.” 

In the recently published FINEARTS-HF trial, patients with heart failure with mildly reduced or preserved ejection fraction showed significant benefits in heart failure outcomes and cardiovascular mortality related to treatment with finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA).

The study specifically showed that finerenone reduced the primary endpoint of worsening heart failure events (unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes by 16% compared with placebo (rate ratio, 0.84; P =.007).

With chronic kidney disease present in approximately 50% of patients with heart failure with mildly reduced or preserved ejection fraction — and associated with higher morbidity and mortality in those patients — the authors further evaluated the drug’s renal effects in a prespecified analysis of the FINEARTS-HF population of 6000 patients with heart failure and a left ventricular ejection fraction of 40% or greater.

They found that, with a median follow-up of 2.6 years, those receiving finerenone had no significant differences vs placebo in the composite kidney outcome of 50% or greater decline in eGFR decline or kidney failure, with low rates in both groups — 75 vs. 55 events, respectively (hazard ratio [HR] 1.33).

The differences were also not statistically significant for the outcome of having 57% or more eGFR decline or kidney failure (41 vs 31 events; HR, 1.28).

Those treated with finerenone did have significantly greater improvements in urine albumin-to-creatinine ratio (UACR), with a 30% greater reduction vs placebo by 6 months, regardless of whether patients had diabetes.

“Overall, these data provide important information on expected changes in kidney biomarkers when prescribing finerenone for patients with heart failure with mildly reduced or preserved ejection fraction,” McCausland said.

In the FINEARTS-HF study, participants were randomized in a 1:1 ratio to treatment with finerenone, up to 20 mg or 40 mg once daily, or a matching placebo, in addition to usual therapy. 

Key exclusion criteria included having an eGFR of 2, potassium level > 5.0 mmol/L, hemoglobin

Patients had a mean eGFR at baseline of 62 mL/min/1.73 m², with about half (48%) having a mean baseline eGFR of less than 60 mL/min/1.73 m², which is indicative of moderate to severe kidney disease.

Baseline UACR data was available for 5797 participants, who had a median baseline UACR of 18 mg/g. 

Whereas 61% had a baseline UACR of less than 30 mg/g, 30% had levels of 30 to less than 300 mg/g, indicating albuminuria, and 10% had macroalbuminuria, with UACR levels of 300 mg/g or higher. 

Despite the lack of a significant difference in the composite kidney outcome, the current analysis showed that among participants with baseline UACR levels below 300 mg/g, finerenone treatment reduced the risk for new onset macroalbuminuria by 38% (HR, 0.62), irrespective of their diabetes status.

Of note, those treated with finerenone group did have increased hyperkalemia episodes, with similar patterns across eGFR categories.

Commenting on the study, Emily Chang, MD, an associate professor of medicine with the Division of Nephrology and Hypertension at the University of North Carolina, Chapel Hill, noted that “i t’s good to have these more diverse tools that can help, depending on what the underlying problems are — whether it’s hypertension, diabetes, or heart failure — and the more we can find out about which of these medicines help, that will really help physicians hone in the priority for this patient. 

“Studies like this are very beneficial in moving the needle a little bit more in our understanding of each of these tools,” she told Medscape Medical News.

Further commenting on the study as a discussant in the session, Ian de Boer, MD, a professor of medicine and endowed chair in Kidney Research at the University of Washington in Seattle, noted the relatively low kidney risk in the study’s population, adding that “chronic kidney disease is a disease that, of course, progresses over years to decades, and [the study] has a relatively short follow-up of the long-term effects in this population.”

Nevertheless, a key contribution of the FINEARTS-HF trial is that ” we now know that despite no large kidney benefits in this population, there are heart failure benefits, and this will lead to an increasing use of finerenone in this population.

“There is debate already in the cardiology field about whether to use a nonsteroidal or steroidal mineralocorticoid receptor antagonist in this population, [but] I think most will agree that having a new tool to treat moderately reduced and preserved ejection heart failure is valuable,” he said. 

McCausland reported relationships with GlaxoSmithKline, Zydus Therapeutics, and research funding from Novartis and Lexicon. De Boer’s disclosures include relationships with Alnylam, AstraZeneca, Boehringer Ingelheim, Dexcom, Lexicon, Lilly, Mitre, and Novo Nordisk.