Limited renal benefit with finerenone in heart failure

SAN DIEGO — In patients with heart failuretreatment with finerenone offers some benefit in reducing the risk of macroalbuminuria. However, no significant changes are seen in kidney-based estimated glomerular filtration rate (eGFR) results, shows an analysis of the recently published FINEARTS-HF trial.

“Among heart failure patients with mildly reduced or preserved ejection fraction in FINEARTS-HF who were at relatively low risk of adverse renal events, finerenone did not change 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, presenting the findings at a press briefing for the American Society of Nephrology (ASN) Kidney Week 2024.

Analysis was simultaneously published in Journal of the American College of Cardiology.

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

In the recently published one FINEARTS-HF processheart failure patients 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 emergency 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 heart failure patients with mildly reduced or preserved ejection fraction—and associated with greater morbidity and mortality in these 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 did not differ significantly from placebo in the composite renal outcome of 50% or greater decline in eGFR or renal failure, with rates decreased in both groups – 75 vs. . 55 events, respectively (hazard ratio (HR) 1.33).

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

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

“Overall, these data provide important information regarding the expected changes in renal biomarkers when finerenone is prescribed for heart failure patients with mildly reduced or preserved ejection fraction,” said McCausland.

In the FINEARTS-HF trial, 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 an eGFR of < 25 ml/min/1.73 m²potassium level > 5.0 mmol/L, hemoglobin < 10 g/dL or symptomatic hypotension.

Patients had a mean baseline eGFR of 62 mL/min/1.73 m²with about half (48%) having a mean baseline eGFR of less than 60 ml/min/1.73 m²which indicates moderate to severe kidney disease.

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

While 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 composite kidney outcome, the current analysis showed that among participants with baseline UACR levels below 300 mg/g, finerenone treatment reduced the risk of new-onset macroalbuminuria by 38% (HR, 0.62), regardless of their diabetes status.

Of note, those treated with the finerenone group increased hyperkalemia episodes, with similar patterns between eGFR categories.

Commenting on the study, Emily Chang, MD, associate professor of medicine in the Division of Nephrology and High blood pressure of the University of North Carolina, Chapel Hill, noted that “it’s good to have these more diverse tools that can help, depending on what the underlying problems are—whether it’s high blood pressure, diabetes, or heart failure—and the more we can learn. about which of these drugs helps, that will really help doctors refine their priority for this patient.

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

Commenting further on the study as a session discussant, Ian de Boer, MD, 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 population, adding that “Chronic kidney disease it’s a disease that, of course, progresses over years to decades, and (the study) has a relatively short follow-up of long-term effects in this population.”

However, a key contribution of the FINEARTS-HF trial is that “we now know that, despite the lack of large benefits for the kidneys in this population, there are benefits for heart failure, and this will lead to increased use of finerenone in this population.

“There is already debate in the field of cardiology regarding the use of a nonsteroidal or steroidal mineralocorticoid receptor antagonist in this population, (but) I think most will agree that having a new tool to treat heart failure with moderately reduced output and preserved 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, Miter, and Novo Nordisk.