Trial Details

Acronym: Aldosterone Targeted NeuroHormonal CombinEd with NAtriuresis Therapy in Heart Failure

Purpose: Evaluated effect of high-dose spironolactone on outcomes including N-terminal pro-B type natriuretic peptide levels in patients with acute HF

Format: Randomized, double blind, placebo-controlled

Treatment Group: high-dose spironolactone

Control Group: placebo (or continued lose-dose spironolactone use)

Number of Patients: 360

Centers: 22

Inclusion Criteria:

  • Admitted to hospital for acute heart failure with at least 1 symptom and 1 sign of congestion
  • Randomized within 24 h of first intravenous diuretic dose
  • Estimated glomerular filtration rate of ≥30 ml/min/1.73 m2
  • Serum potassium concentration of ≤5.0 mmol/l
  • NT-proBNP ≥1,000 pg/ml or BNP ≥250 pg/ml
  • Not on mineralocorticoid receptor antagonists or on low-dose spironolactone

Exclusion Criteria:

  • Taking eplerenone or >25 mg spironolactone at baseline
  • Estimated glomerular filtration rate <30 ml/min/1.73 m2
  • Serum potassium concentration of >5.0 mmol/l.
  • Systolic blood pressure <90 mm Hg
  • Hemodynamically significant arrhythmias or defibrillator shock within 1 week
  • Acute coronary syndrome currently suspected or within the past 4 weeks
  • Severe liver disease (ALT or AST >3× normal, alkaline phosphatase or bilirubin >2× normal)
  • Current intravenous inotrope use
  • Complex congenital heart disease
  • Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or cardiac tamponade

Primary Endpoint: proportional change in NT-proBNP from randomization to 96 hours

Secondary Endpoints:

  • Clinical congestion score
  • Dyspnea relief
  • Net urine output
  • Weight change
  • Loop diuretic dose need in furosemide dose equivalents
  • Development of in-hospital worsening HF


The ATHENA-HF trial found at 96 hours or discharge, change in log NT-pro BNP was –0.49 (95% CI, –0.98-–0.14) in the usual care group and –0.55 (95% CI, –0.92-–0.18) in the high-dose spironolactone group (P = .57). Absolute changes in NT-proBNP at 96 hours or discharge were –1,072 pg/mL (95% CI, –3,182-–231) in the usual care group and –1796 (95% CI, –3883-–571) in the high-dose spironolactone group (P = .76).

Original Publication:

Butler J, et al. JACC Heart Fail. 2016:doi;10.1016/j.jchf.2016.06.003.

Healio/Cardiology News Coverage:

ATHENA-HF: High-dose spironolactone does not benefit patients with acute HF