No Kidney Benefit With Finerenone in Heart Failure Patients

SAN DIEGO — Finerenone (Kerendia) yielded minimal renal benefit in patients with heart failure with mildly reduced or preserved ejection fraction, according to a secondary analysis of the FINEARTS-HF trial.

In fact, incidence of a prespecified composite kidney outcome — a sustained ≥50% decline in estimated glomerular filtration rate (eGFR) or kidney failure — was numerically higher with finerenone (75 vs 55 events with placebo; HR 1.33, 95% CI 0.94-1.89).

It was a similar story in an analysis that included a ≥57% eGFR decline or kidney failure (41 vs 31 events, respectively; HR 1.28, 95% CI 0.80-2.05), Finnian R. McCausland, MBBCh, MMSc, of Brigham and Women’s Hospital in Boston, reported here.

However, patients in the phase III study were already “at relatively low risk of adverse kidney events,” noted McCausland, in a presentation at the American Society of Nephrology Kidney Week meeting.

“Chronic kidney disease (CKD) is present in around 50% of patients with heart failure with mildly reduced or preserved ejection fraction and is associated with higher morbidity and mortality compared to those without CKD,” McCausland pointed out. He added that in this patient population, the presence and magnitude of albuminuria is a “potent predictor” of cardiovascular (CV) and kidney outcomes.

While finerenone didn’t move the needle on the composite kidney outcomes, the anti-mineralocorticoid agent was favored over placebo when it came to reducing the risk of new-onset microalbuminuria (HR 0.76, 95% CI 0.68-0.83) and macroalbuminuria (HR 0.62, 95% CI 0.53-0.73).

Finerenone also reduced urine albumin-creatinine ratio (UACR) by 30% (95% CI 25-34) over 6 months compared with placebo, which was largely maintained throughout the 36-month follow-up.

Data from the study were simultaneously published in the Journal of the American College of Cardiology.

“One could speculate that with albuminuria lowering, there may ultimately be longer-term eGFR benefits,” commented Ian de Boer, MD, MS, of the University of Washington in Seattle, who was not involved with the study. But, he added, “substantial eGFR benefits are unlikely in this low-risk kidney population based on the results we’ve seen.”

“CKD is a disease that of course progresses over years to decades,” he added. “We had relatively short follow-up in the long-term effects of finerenone in this population. We do have some uncertainty.”

In 2021, finerenone became the first non-steroidal, selective mineralocorticoid receptor antagonist approved to reduce the risk of sustained eGFR decline, end-stage kidney disease, CV death, non-fatal myocardial infarction, and hospitalization for heart failure in adults with CKD associated with type 2 diabetes.

According to the primary analysis of FINEARTS-HF, presented earlier this year at the European Society of Cardiology meeting, finerenone significantly reduced the risk of urgent or unplanned heart failure care and death from cardiovascular causes (rate ratio 0.84, 95% CI 0.74-0.95).

For study inclusion, participants had to be 40 or older with symptomatic heart failure and have a left ventricular (LV) ejection fraction ≥40%, evidence of structural heart disease (LV hypertrophy or left atrial enlargement within 12 months), and elevated serum concentration of natriuretic peptides.

At baseline, the 6,001 participants randomized had an average eGFR of 62±20 mL/min/1.73 m² (eGFRs <25 were excluded). Over half had an eGFR ≥60 mL/min/1.73 m² (n=3,113; mean age around 69), while about a quarter had an eGFR of 45 to <60 mL/min/1.73 m² (n=1,556; mean age around 74) and about one-fifth had an eGFR <45 mL/min/1.73 m² (n=1,332; mean age 77).

The majority of participants were white and more than half were previously hospitalized for heart failure. Most were on a beta-blocker and loop diuretic at baseline.

In the analysis presented by McCausland, treatment with finerenone led to an acute decline in eGFR during the initial 3 months of treatment (-2.9 mL/min/1.73 m² vs placebo), but the eGFR slope difference was nonsignificant between groups from month 3 to the end of the study (0.2 mL/min/1.73 m² per year).

Overall, the frequency of serious adverse events (AEs) was similar between the two study arms. As expected, serious AEs, elevations in serum creatinine ≥3.0 mg/dL, and AEs related to hyperkalemia were more frequent among patients with lower baseline eGFRs.

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