Effects of Finerenone on Natriuretic Peptide Levels in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: The FINEARTS-HF Trial
Jonathan W. Cunningham, Brian Claggett, Muthiah Vaduganathan, Akshay S. Desai, Pardeep S. Jhund, Carolyn Lam, Michele Senni, Sanjiv J. Shah, Adriaan A. Voors, Faiez Zannad, Bertram Pitt, Flaviana Amarante, James Lay‐Flurrie, Katja Rohwedder, Laura Goea, Mario Berger, John J.V. McMurray, Scott D. Solomon
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.