Effects of finerenone on natriuretic peptide levels in heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

Abstract

AIMS N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations serve as markers of prognosis and therapeutic response in patients with heart failure (HF). The effect of the non-steroidal mineralocorticoid receptor antagonist finerenone on NT-proBNP in patients with HF with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) is currently unknown. METHODS AND RESULTS The FINEARTS-HF trial randomized patients with HFmrEF/HFpEF and NT-proBNP ≥300 pg/ml (≥900 pg/ml if atrial fibrillation) or B-type natriuretic peptide ≥100 pg/ml (≥300 pg/ml if atrial fibrillation) to finerenone versus placebo. Core laboratory NT-proBNP was measured at baseline, 3, and 12 months after randomization. We evaluated the association between log-transformed NT-proBNP and the primary outcome (cardiovascular death and total HF events), whether baseline NT-proBNP modified the effect of finerenone on this outcome, and the effect of finerenone on NT-proBNP concentration. Baseline NT-proBNP was available in 5843 of 6001 patients analysed (median 1041 [interquartile range 449-1946] pg/ml) and was strongly associated with risk of the primary outcome (adjusted rate ratio 1.44 per doubling in biomarker concentration, 95% confidence interval [CI] 1.37-1.51], p < 0.001). Baseline NT-proBNP did not modify the benefit of finerenone on the primary outcome (pinteraction = 0.92). Finerenone reduced NT-proBNP by 12.1% (95% CI 8.5-15.4%) at 3 months and 12.5% (95% CI 8.1-16.7%) at 12 months, compared to placebo. CONCLUSIONS In patients with HFmrEF/HFpEF, finerenone reduced NT-proBNP within months of initiation, and improved clinical outcomes regardless of baseline NT-proBNP concentration. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov NCT04435626, EudraCT 2020-000306-29.