Does Finerenone’s Efficacy Diminish if Initiated Late in Heart Failure?

The benefit-risk profile of finerenone (Kerendia) for heart failure and mildly reduced or preserved ejection fraction (HFmrEF, HFpEF) was arguably unchanged with delayed initiation, according to the FINEARTS-HF trial.

An analysis by time since a patient’s worsening heart failure (WHF) event showed that the efficacy of finerenone at reducing the primary composite outcome appeared best if the patient had been enrolled within 7 days of WHF (RR 0.74 relative to placebo, 95% CI 0.57-0.95). The effect estimate went down numerically as more time elapsed, reaching a nonsignificant low for those enrolled over 3 months after the WHF event (RR 0.99, 95% CI 0.81-1.21).

Formally, however, this pattern did not reach statistical significance as a treatment-by-time interaction (P=0.07), reported Akshay Desai, MD, MPH, of Brigham and Women’s Hospital and Harvard University, both in Boston, during a late-breaking trial session held virtually by the Heart Failure Society of America (HFSA).

This FINEARTS-HF prespecified analysis was simultaneously published in the Journal of the American College of Cardiology (JACC).

Notably, there was no change in one’s risk of adverse events on finerenone whether there had been a recent WHF or not. “Finerenone similarly increased risk of hypotension, hyperkalemia, and worsening renal function and lowered risk of hypokalemia in those with and without recent WHF,” Desai said.

Even so, until there is evidence to suggest significant benefit in patients enrolled over 3 months after a WHF event, HFSA immediate past-president John Teerlink, MD, of San Francisco Veterans Affairs Medical Center, said he saw “no compelling need to initiate finerenone in these patients who have no recent WHF event.”

More importantly, session discussant Teerlink stressed that the trial reinforces the benefit of initiating HF therapies in-hospital or within the week to significantly improve the care and outcomes of patients.

The significance of the early post-WHF period was explained by Felix Lindberg, MD, PhD, and Gianluigi Savarese, MD PhD, both of Karolinska Institutet in Stockholm, in an accompanying JACC editorial comment.

“First, given the high event rate during the post-WHF period, even modest reductions in relative risk can translate into substantial absolute risk reductions. Second, for the large proportion of patients with HFpEF managed predominantly in primary care, a WHF event might be one of few opportunities for accessing specialized cardiology care, which is a crucial moment to optimize pharmacological management,” they wrote.

In 2021, the FDA approved finerenone for renal and cardiovascular protection in adults with chronic kidney disease associated with type 2 diabetes.

The nonsteroidal mineralocorticoid receptor antagonist (MRA) appears poised for expansion into HF after FINEARTS-HF became the first MRA trial to meet its primary endpoint in patients with ejection fractions above 40%.

The study’s main finding, reported this summer, had been finerenone’s significant reduction of combined urgent or unplanned HF care and death from cardiovascular causes in HFmrEF and HFpEF — albeit driven by fewer first or repeat worsening HF events, not deaths.

According to another late-breaker from the HFSA conference, finerenone worked consistently across the range of mildly reduced and preserved ejection fractions in FINEARTS-HF.

Additionally, finerenone’s benefit in the trial could be detected as early as 1 month after initiation based on another study, while a separate prespecified analysis projected up to 2 or 3 years of extra survival free from cardiovascular death or a worsening HF event if people used the medication long-term.

Yet another report associated the drug with quality-of-life improvements no matter the person’s baseline symptoms.

The 6,000-person, double-blind FINEARTS-HF trial enrolled people with a median age of 73; 54.5% were men. These were hospitalized or ambulatory individuals with ejection fractions over 40%.

By time since WHF, there were 20.3% of patients enrolled within 7 days, 33.8% between 7 days and 3 months, and 15.6% more than 3 months out. Meanwhile, 30.3% had no prior history of WHF.

The more recent the study participant’s last WHF, the greater the risk of mortality, cardiovascular death, and HF events.

Lindberg and Savarese called it “reassuring” that “treatment initiation in close proximity to a WHF event is both safe and beneficial” based on the trial.

“Since FINEARTS-HF was not designed to test for effect modification in WHF versus chronic HF, and no significant interaction was detected, it is prudent to neither confirm nor the exclude the possibility of a post-WHF time-dependent efficacy,” the duo nevertheless cautioned.

This year’s in-person HFSA meeting, originally planned for Atlanta, was cancelled due to Hurricane Helene.