Short-term discontinuation of finerenone attenuates treatment effect
ESC Heart Failure 2025 – A FINEARTS-HF trial analysis among HFmrEF/HFpEF patients showed long-term finerenone treatment reduced the risk of CV events compared with placebo, but this benefit appeared to decrease after study drug withdrawal for 30 days.
This summary is based on the presentation of Muthiah Vaduganathan, MD (Boston, MA, USA) at the ESC Heart Failure Congress 2025 - Blinded Withdrawal of Finerenone after Long-Term Treatment in FINEARTS-HF.
Introduction and methods
Clinical guidelines on HF recommend continuing HF therapies indefinitely in HF patients to prevent disease relapse. Even if clinicians and/or patients wish to terminate the medications over time, experience with discontinuation is limited. To address this knowledge gap, the design of the FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) trial included a blinded drug withdrawal phase.
The FINEARTS-HF trial was a global, double-blind, placebo-controlled, phase 3 RCT in which 6001 patients with HFmrEF or HFpEF, NYHA class II–IV HF symptoms, LVEF ≥40%, evidence of structural heart disease, and elevated NT-proBNP levels were randomized to finerenone (maximum dose: 20 or 40 mg once daily based on eGFR) or placebo, in addition to usual care. Median follow-up duration was 2.6 years.
After the double-blind period, all patients who were still partaking in the trial were withdrawn from the study drug and entered a posttreatment follow-up period for 30 days to collect adverse event data (n=3742). They remained blinded to the study drug they had previously received. The key safety endpoint of the blinded drug withdrawal phase was CV serious adverse events or any adverse event leading to death.
Main results
- Baseline characteristics of patients in the withdrawal cohort were well balanced between the group that had been treated with finerenone (n=1890) and the group that had received placebo (n=1852).
- In the group of patients previously on placebo, the risk of the key safety endpoint did not differ between the prewithdrawal phase (i.e., measured from prior to beginning of close-out period to end of double-blind treatment period; mean duration: 101 days) and the withdrawal phase (mean ± SD duration: 30 ± 5 days) (HR: 1.20; 95%CI: 0.60–2.41).
- However, in the finerenone withdrawal group, this risk was increased (HR: 2.80; 95%CI: 1.44–5.45; P for time-by-treatment interaction=0.006).
- The treatment effect of finerenone versus placebo on CV risk reduction was still apparent in the prewithdrawal phase (incidence rate: 6.0 vs. 9.2 events per 100 persons-years; HR: 0.65; 95%CI: 0.41–1.05).
- In the withdrawal phase, however, the risk of CV events was higher in the finerenone group than the placebo group (incidence rate: 20.8 vs. 11.2 events per 100 persons-years; HR: 1.85; 95%CI: 1.03–3.34; P for time-by-treatment interaction=0.006).
Conclusion
This analysis of the FINEARTS-HF trial among HFmrEF/HFpEF patients showed long-term treatment with finerenone reduced the risk of CV events compared with placebo, but this benefit appeared to decrease after short-term drug withdrawal. In addition, the rate of CV serious adverse events or any adverse event leading to death increased after discontinuation of finerenone but not placebo. According to Dr. Vaduganathan, “these data bolster current guidelines on the need for maintenance of HF medical therapies to maximize long-term treatment gains, even in a clinically stable individual and even in the setting of HFpEF.”
- Our reporting is based on the information provided at the ESC Heart Failure Congress 2025 -