Clinical correlates and outcomes associated with B-type natriuretic peptide changes and their interaction with eplerenone in acute heart failure: findings from the EARLEIR trial

Abstract Background B-type natriuretic peptide (BNP) is a well-established marker to reflect the severity of heart failure (HF) that predicts morbidity and mortality. However, clinical significance of BNP changes and its interaction with eplerenone in acute HF (AHF) remains unclear. Methods The EARLIER trial included patients with AHF randomized to receive eplerenone or placebo over 6 months. Multivariable linear regression was used to assess the association between BNP changes during hospitalization and changes in echocardiographic parameters or Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. The primary outcome was the composite of cardiovascular death, HF hospitalization, investigator-reported worsening HF and out-of-hospital diuretic intensification. Results Among 267 patients (mean age: 67±13years; 73% male), mean left ventricular ejection fraction was 31±8%. From admission to discharge, BNP levels significantly decreased (371 181-624 pg/mL vs. 223 106-377 pg/mL; P0.001). Greater reductions in BNP were associated with greater improvements in echocardiographic indices of left ventricular filling pressure, LVEF and KCCQ overall score (all-P0.05). After adjusting for these BNP-associated variables, BNP reduction was associated with improved outcomes (adjusted-HR per 50 pg/mL decrease, 95%CI=0.87, 0.80-0.95). Eplerenone significantly reduced BNP levels (P=0.03) and lowered the risk of study-outcome compared to placebo (HR, 95%CI=0.49, 0.26-0.93). This benefit was more pronounced in patients achieving a successful reduction in BNP (25% drop) (P-for-interaction0.05). Conclusion In AHF, BNP changes correlated with clinical stability and independently predicted prognosis. Eplerenone lowered BNP levels compared to placebo, leading to favorable outcomes. These data highlight that BNP changes are potential target for AHF, which may be treatable with eplerenone.