Impact of timing of worsening HF events and treatment effect of finerenone in HFmrEF/HFpEF

A secondary analysis of FINEARTS-HF in HFmrEF/HFpEF patients revealed those with recent HF worsening had a higher risk of CV death or total worsening HF events but also appeared to experience greater absolute benefit from finerenone compared with placebo.

This summary is based on the publication of Desai AS, Vaduganathan M, Claggett BL, et al. - Finerenone in Patients With a Recent Worsening Heart Failure Event: The FINEARTS-HF Trial. J Am Coll Cardiol. 2025 Jan 21;85(2):106-116. doi: 10.1016/j.jacc.2024.09.004

Introduction and methods

Background

HF patients with worsening heart failure events (WHFEs) are at increased risk of CV events and mortality [1-4]. Clinical guidelines therefore recommend in-hospital or early postdischarge optimization of GDMTs, particularly in patients with HFrEF [5,6]. However, the benefit of intensive pharmacotherapy in patients with HFmrEF or HFpEF who have experienced a recent WHFE remains to be established.

The FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) trial recently demonstrated the nonsteroidal MRA finerenone reduced the risk of the composite outcome of total WHFEs or CV death compared with placebo in patients with HFmrEF/HFpEF [7].

Aim of the study

In a prespecified secondary analysis of the FINEARTS-HF trial, the authors examined the efficacy and safety of finerenone in relation to the recency of a WHFE.

Methods

The FINEARTS-HF trial was an international, double-blind, placebo-controlled, phase 3 RCT in which 6001 HFmrEF/HFpEF patients—both hospitalized and ambulatory—with 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 32 months.

Outcomes

The primary efficacy endpoint was a composite outcome of CV death or total (first and recurrent) WHFEs (i.e., HF hospitalization or urgent HF visit). Key secondary efficacy endpoints included the individual components of the primary endpoint, a composite renal outcome (defined as sustained eGFR decline ≥50%, sustained eGFR decline to <15 mL/min/1.73 m², or initiation of chronic dialysis or renal transplantation), and all-cause mortality.

The primary safety endpoint of the current analysis was the incidence of adverse events leading to discontinuation of the study drug. Other safety endpoints were renal dysfunction, hypokalemia, hyperkalemia, and hypotension.

Main results

Efficacy

• The time from WHFE to randomization was inversely related to the risk of the primary composite endpoint, with rates ranging from 24.4 per 100 patient-years (95%CI: 21.4–27.8) in patients enrolled during the WHFE (n=749; 12.5%) or within 7 days of the WHFE (n=470; 7.8%) to 11.3 per 100 patient-years (95%CI: 10.2–12.4) in those enrolled >3 months of the WHFE (n=937; 15.6%) or with no prior WHFE (n=1817; 30.3%) (risk ratio (RR): 2.13; 95%CI: 1.82–2.55).
• Similar patterns were seen for the secondary efficacy endpoints.
• There was a trend toward a lower risk of the primary endpoint with finerenone versus placebo in patients enrolled <7 days of the WHFE (RR: 0.74; 95%CI: 0.57–0.95) or between 7 days and 3 months of the WHFE (n=2028; 33.8%) (RR: 0.79; 95%CI: 0.64–0.97) compared with patients enrolled >3 months or with no prior WHFE (RR: 0.99; 95%CI: 0.81–1.21). However, no formal statistical interaction between treatment assignment and time from WHFE was observed (P for interaction=0.07).
• Absolute risk reductions with finerenone versus placebo were 7.8 per 100 patient-years (95%CI: 1.4−14.1) for patients enrolled <7 days of the WHFE, 4.6 per 100 patient-years (95%CI: 0.3−8.8) for those enrolled between 7 days and 3 months of the WHFE, and 0.1 per 100 patient-years (95%CI: −2.2 to 2.4) for those enrolled >3 months or with no prior WHFE (P for trend=0.011).

Safety

• The rate of adverse events leading to study drug discontinuation appeared to be higher for finerenone versus placebo in patients enrolled >3 months or with no prior WHFE (OR: 1.62; 95%CI: 1.06–2.47) compared with those enrolled <7 days of the WHFE (OR: 0.94; 95%CI: 0.48–1.84), and those enrolled between 7 days and 3 months of the WHFE (OR: 0.76; 95%CI: 0.44–1.33), but this trend was not statistically significant (P for interaction=0.07).
• Similarly, there were no formal statistical treatment-by-time interactions for any of the other safety endpoints (all P for interaction>0.05).

Conclusion

In this prespecified secondary analysis of the FINEARTS-HF trial among HFmrEF/HFpEF patients, participants who were enrolled <7 days of an WHFE had a 2-fold increased risk of the primary composite endpoint of CV death or total WHFEs compared with those enrolled >3 months of the WHFE or with no prior WHFE. Treatment with finerenone versus placebo appeared to lower this risk to a greater extent in patients with a recent WHFE—as indicated by greater absolute risk reductions—although no definitive treatment-by-time interaction could be confirmed. The time from WHFE to randomization also did not affect the safety profile of finerenone.

According to the authors, “these data underscore that the occurrence of worsening HF in any context heralds an inflection point in risk for patients with HFmrEF and HFpEF, and should prompt consideration of treatment intensification.”

Find this article online at J Am Coll Cardiol.

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