Aldosterone Targeted NeuroHormonal Combined With Natriuresis Therapy – Heart Failure - ATHENA-HF

Contribution To Literature:

The ATHENA-HF trial failed to show that high-dose spironolactone was superior to placebo at reducing NT-proBNP levels.


The goal of the trial was to evaluate treatment with a high-dose mineralocorticoid receptor antagonist (MRA) compared with placebo among patients admitted with acute heart failure.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Stratified

Patients with acute heart failure were randomized to spironolactone 100 mg daily (n = 182) versus placebo/low-dose spironolactone (n = 178). Patients not on a MRA at baseline were randomized to high-dose spironolactone versus placebo, while patients on a low-dose MRA at baseline were randomized to high-dose spironolactone versus low-dose spironolactone.

  • Total number of enrollees: 360
  • Duration of follow-up: 60 days
  • Mean patient age: 65 years
  • Percentage female: 36%
  • Percentage with diabetes: 40%

Inclusion criteria:

  • Patients ≥21 years of age with signs/symptoms of pulmonary congestion
  • Estimated glomerular filtration rate ≥30 cc/min/1.73 m2 
  • Serum potassium ≤5.0 mmol/L
  • N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥1000 pg/ml or BNP ≥250 pg/ml
  • No MRAs or only low-dose MRA at baseline
  • Randomization within 24 hours of first intravenous diuretic dose

Exclusion criteria:

  • Spironolactone or eplerenone >25 mg at baseline
  • Systolic blood pressure <90 mm Hg
  • Recent arrhythmias or implantable cardioverter-defibrillator (ICD) shock
  • Recent acute coronary syndrome
  • Current or planned left ventricular assist device
  • Current or planned cardiac transplant
  • Current inotrope use

Other salient features/characteristics:

  • Angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker at baseline: 58%
  • Beta-blocker at baseline: 74%
  • Mean left ventricular ejection fraction (LVEF): 30%

Principal Findings:

The primary outcome, log change in NT-proBNP at 96 hours, was -0.55 in the spironolactone group versus -0.49 in the placebo group (p = 0.57).

Secondary outcomes:

  • Change in dyspnea scale (Likert scale): 15 in the spironolactone group versus 15 in the placebo group (p = 0.61)
  • Net urine output: 6.1 L in the spironolactone group versus 5.6 L in the placebo group (p = 0.57)
  • Change in potassium: 0.3 mEq in the spironolactone group versus 0.2 mEq in the placebo group (p = 0.08)


Among patients admitted with acute heart failure, high-dose spironolactone was not effective at reducing NT-proBNP levels. Secondary outcomes, including dyspnea, urine output, and change in potassium, were also similar between treatment groups.

The current use of MRAs is for optimally treated patients with chronic heart failure (LVEF ≤35% with heart failure symptoms or LVEF ≤40% after myocardial infarction with heart failure symptoms or diabetes).


Efficacy and Safety of Spironolactone in Acute Heart Failure: The ATHENA-HF Randomized Clinical Trial. JAMA Cardiol 2017;Jul 12:[Epub ahead of print].

Presented by Dr. Javed Butler at the American Heart Association Annual Scientific Sessions (AHA 2016), New Orleans, LA, November 16, 2016.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: AHA Annual Scientific Sessions, Acute Disease, Aldosterone, Diabetes Mellitus, Diuretics, Dyspnea, Heart Failure, Mineralocorticoid Receptor Antagonists, Myocardial Infarction, Natriuretic Peptide, Brain, Peptide Fragments, Potassium, Secondary Prevention, Spironolactone, Standard of Care, Stroke Volume, Urine

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