Finerenone benefits in HFpEF may be greater in patients with recent worsening HF

Key takeaways:

• In patients with HF and LVEF 40% or greater, finerenone may have the most benefit in those with recent worsening HF.
• The trend may be due to a play of chance and more data are needed.

In patients with HF and left ventricular ejection fraction 40% or greater, the absolute risk reduction for total worsening HF events and CV death with finerenone vs. placebo was greatest in those with recent worsening HF, new data show.

However, no formal treatment interaction was observed in terms of relative risk reduction, according to a new analysis of patients from the FINEARTS-HF trial.

As Healio previously reported, in the main results of FINEARTS-HF, the nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia, Bayer) reduced risk for CV death and worsening HF by 16% compared with placebo at 32 months. Akshay S. Desai, MD, MPH, FACC, FHFSA, cardiovascular medicine specialist and director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, presented a prespecified analysis of the results stratified by recency of worsening HF during a virtual late-breaking clinical research session of the Heart Failure Society of America Annual Scientific Meeting. The in-person meeting was canceled due to Hurricane Helene.

Recent worsening HF

Akshay S. Desai

“FINEARTS-HF was unique among trials enrolling patients with HF and left ventricular EF 40% or more in that we deliberately targeted enrollment of patients with recent worsening HF events,” Desai told Healio. “Patients were eligible for enrollment during hospitalization for worsening HF or shortly after discharge from treatment for a worsening HF event, and enrollment of those without recent worsening HF was prospectively capped at about 50% of the total study enrollment. Accordingly, nearly half of the enrolled participants had experienced a recent worsening HF event (within 3 months of randomization) and about 12% were enrolled during a worsening HF event/hospitalization. These patients with worsening HF are known to be at high risk for subsequent morbidity and mortality and are a prime target for implementation of disease-modifying therapy. We therefore prespecified an analysis of the interaction between treatment and time from worsening HF to randomization as part of the study statistical analysis plan.”

The analysis, simultaneously published in the Journal of the American College of Cardiology, included 1,219 patients with a worsening HF event within 7 days before randomization, 2,028 patients with a worsening HF event between 7 days and 3 months before randomization and 2,754 patients who had a worsening HF event more than 3 months before randomization or no history of worsening HF events. The mean age was 72 years and the percentage of women ranged from 46% to 48%.

The primary outcome of CV death and total HF events (hospitalizations or urgent visits) favored the finerenone group in patients with a worsening HF event within 7 days before randomization (RR = 0.74; 95% CI, 0.57-0.95) and in patients with a worsening HF event between 7 days and 3 months (RR = 0.79; 95% CI, 0.64-0.97) but not in patients with a worsening HF event more than 3 months before randomization or no history of worsening HF events (RR = 0.99; 95% CI, 0.81-1.21), Desai said during the presentation.

However, he said, there was no formal treatment interaction (P for interaction = .07).

In a time-to-first event analysis, the treatment interaction was less pronounced (P for interaction = .46), he said.

Yet, the absolute risk reduction for the primary outcome conferred by finerenone did significantly vary by recency of worsening HF event (within 7 days, absolute RR per 100 patient-years = 7.8; 95% CI, 1.4-14.1; 7 days to 3 months, absolute RR per 100 patient-years = 4.6; 95% CI, 0.3-8.8; more than 3 months or no history, absolute RR per 100-patient years = 0.1; 95% CI, –2.2 to 2.4; P for trend = .01), he said.

High-risk population

“Patients with recent worsening HF (regardless of the treatment setting) are at high risk for subsequent readmission and mortality,” Desai told Healio. “These patients appear to derive benefit from finerenone regardless of their proximity to a worsening HF event, but those enrolled during or early after a recent worsening HF event appear to experience the greatest absolute risk reductions with finerenone, without any enhanced signal of adverse events. These data suggest that patients with recent worsening heart failure may experience a particularly favorable balance of benefit to risk from finerenone treatment and may be prime candidates for treatment with finerenone in clinical practice.”

Desai told Healio that “the lack of a compelling statistical interaction in these subgroups and the lack of consistency of this trend in other key secondary endpoints examined” mean that the researchers cannot rule out that the increased benefit of finerenone in patients with recent worsening HF is a chance finding, so more data from patients in the hospital with HF or recently discharged for it are necessary, and the REDEFINE-HF and CONFIRMATION-HF trials may provide that.

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