Early changes in albuminuria and their interaction with eplerenone treatment in patients hospitalized for acute heart failure: findings from the EARLIER trial

Abstract Background Patients hospitalized for acute heart failure (AHF) have high degrees of congestion, which may be associated with albuminuria. Mineralocorticoid receptor antagonists (MRAs) have natriuretic effects, possibly diminishing the degree of albuminuria. However, early changes in albuminuria, their prognostic value and interaction with MRA therapy remain unclear. Methods The EARLIER trial included patients with AHF who were randomized to receive eplerenone or placebo over 6 months. Urine albumin-to-creatinine ratio (UACR) at admission and week 1 were measured, and Cox proportional hazards models were used for analyses. Results Among 296 patients (mean age, 67±13years; 75% male), median B-type natriuretic peptide was 332 (145-529) pg/ml, and mean left ventricular ejection fraction was 30±8%. Patients with an UACR of ≥30 mg/g at admission had more severe signs and symptom of congestion compared to those without (all-P0.01). From admission to week 1, UACR levels significantly decreased (P0.01), without significant differences between treatment groups (P0.10). UACR levels at both admission (adjusted-HR 95% CI=1.23 1.03-1.47) and week 1 (adjusted-HR 95% CI=1.23 1.01-1.50) were associated with the risk of cardiovascular death and hospitalization over 6 months. Additionally, eplerenone vs. placebo reduced the risk of a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF, and out-of-hospital diuretic intensification (HR 95% CI= 0.53 0.29-0.97), regardless of the albuminuria severity (P-for-interaction0.10). Conclusion In patients with AHF, the degree of albuminuria at both admission and week 1 was associated with post-discharge prognosis. Although eplerenone did not reduce albuminuria levels, the benefit from eplerenone was consistent regardless of the albuminuria severity.