Finerenone and Outpatient Worsening Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial.

Importance: Worsening heart failure (HF) is commonly managed in the outpatient setting with adjustments in oral diuretic therapy. The effect of the nonsteroidal mineralocorticoid receptor antagonist finerenone on outpatient worsening HF events in patients with mildly reduced or preserved ejection fraction is unknown.

Objective: To evaluate the effect of finerenone on outpatient worsening HF events requiring oral diuretic intensification among patients with HF with mildly reduced or preserved ejection fraction.

Design, setting, and participants: This is a secondary analysis of the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), a global, multicenter randomized clinical trial. Patients had HF and an ejection fraction of 40% or greater. Data analysis was conducted from September 1 to December 10, 2024.

Intervention: Participants were randomized 1:1 to finerenone or placebo.

Main outcomes and measures: Primary outcome events (cardiovascular death, HF hospitalization, and outpatient urgent HF visit requiring intravenous diuretic therapy) were centrally adjudicated. In this prespecified analysis, outpatient oral diuretic intensification events were defined as initiations of loop or thiazide diuretic or increases in loop diuretic dosage. The risk of all-cause death following each type of worsening HF event (HF hospitalization, urgent HF visit, or outpatient oral diuretic intensification) and the effect of finerenone on outpatient oral diuretic intensification alone or as part of an extended composite outcome with primary outcome events were evaluated.

Results: A total of 6001 participants (mean [SD] age, 72.0 [9.6] years; 2732 [46%] female) were enrolled. First worsening HF events included 664 HF hospitalizations, 87 urgent HF visits, and 1250 oral diuretic intensifications. Rates of death were higher following worsening HF: 27.7 (95% CI, 24.3-31.5) per 100 patient-years after HF hospitalization, 13.6 (95% CI, 8.8-21.1) per 100 patient-years after urgent HF visit, and 11.6 (95% CI, 10.2-13.1) per 100 patient-years after outpatient oral diuretic intensification compared with 4.5 (95% CI, 4.2-4.9) per 100 patient-years for patients without worsening HF. Adding outpatient oral diuretic intensification to the primary outcome increased the number of patients experiencing events from 1343 to 2238. Finerenone reduced outpatient oral diuretic intensification alone (hazard ratio [HR], 0.89 [95% CI, 0.80-0.98]; P = .02) and in an extended composite outcome that further included cardiovascular death, HF hospitalization, and urgent HF visit (HR, 0.85 [95% CI, 0.78-0.92]; P < .001).

Conclusions and relevance: Outpatient worsening HF events requiring oral diuretic intensification were common, associated with poor prognosis, and reduced by finerenone in patients with HF with mildly reduced or preserved ejection fraction.

Trial registration: ClinicalTrials.gov Identifier: NCT04435626.