Circ Heart Fail. 2026 Jan 29:e013201. doi: 10.1161/CIRCHEARTFAILURE.125.013201. Online ahead of print.
ABSTRACT
BACKGROUND: The prevalence and prognostic significance of liver biomarkers in heart failure (HF) with mildly reduced or preserved ejection fraction are uncertain, with both potential hemodynamic and metabolic contributions to liver dysfunction in these patients. We evaluated the prevalence and prognostic value of liver biomarkers and assessed the effects of the nonsteroidal mineralocorticoid receptor antagonist finerenone on these biomarkers and clinical outcomes, in FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure).
METHODS: FINEARTS-HF was a randomized, double-blind, placebo-controlled trial that enrolled 6001 patients with left ventricular ejection fraction ≥40%, evidence of structural heart disease, and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Liver biomarkers examined were total bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase.
RESULTS: Among 5873 patients with available baseline bilirubin measurements, 11.9% had elevated levels (>1.0 mg/dL). Higher bilirubin levels were associated with a greater risk of total worsening HF events and cardiovascular death. Compared with placebo, finerenone rapidly reduced bilirubin and alkaline phosphatase levels (but not transaminase levels), with effects sustained over time. Finerenone reduced the risk of total worsening HF events and cardiovascular death across all bilirubin tertiles (T1 [<0.4 mg/dL], rate ratio 0.94 [95% CI, 0.75-1.17]; T2 [0.5-0.6 mg/dL], 0.83 [0.66-1.05]; T3 [≥0.7 mg/dL], 0.77 [0.62-0.97]), with no significant interaction by bilirubin level (Pinteraction=0.43). Consistent effects were observed for the components of the primary outcome, all-cause death, and improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score.
CONCLUSIONS: Baseline bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of finerenone on morbidity and mortality in HF with mildly reduced or preserved ejection fraction. Finerenone reduced bilirubin and alkaline phosphatase, suggesting a possible decongestive effect in HF with mildly reduced or preserved ejection fraction.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04435626.
PMID:41608790 | DOI:10.1161/CIRCHEARTFAILURE.125.013201