Rationale and Design of the ATHENA-HF Trial: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure

Javed Butler, Adrian F. Hernandez, Kevin J. Anstrom, Andreas Kalogeropoulos, Margaret May Redfield, Marvin A. Konstam, W. H Wilson Tang, G. Michael Felker, Monica R. Shah, Eugene Braunwald

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Although therapy with mineralocorticoid receptor antagonists (MRAs) is recommended for patients with chronic heart failure (HF) with reduced ejection fraction and in post-infarction HF, it has not been studied well in acute HF (AHF) despite being commonly used in this setting. At high doses, MRA therapy in AHF may relieve congestion through its natriuretic properties and mitigate the effects of adverse neurohormonal activation associated with intravenous loop diuretics. The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) trial is a randomized, double-blind, placebo-controlled study of the safety and efficacy of 100 mg/day spironolactone versus placebo (or continued low-dose spironolactone use in participants who are already receiving spironolactone at baseline) in 360 patients hospitalized for AHF. Patients are randomized within 24 h of receiving the first dose of intravenous diuretics. The primary objective is to determine if high-dose spironolactone, compared with standard care, will lead to greater reductions in N-terminal pro−B-type natriuretic peptide levels from randomization to 96 h. The secondary endpoints include changes in the clinical congestion score, dyspnea relief, urine output, weight change, loop diuretic dose, and in-hospital worsening HF. Index hospital length of stay and 30-day clinical outcomes will be assessed. Safety endpoints include risk of hyperkalemia and renal function. Differences among patients with reduced versus preserved ejection fraction will be determined. (Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure [ATHENA-HF]; NCT02235077)

Original languageEnglish (US)
Pages (from-to)726-735
Number of pages10
JournalJACC: Heart Failure
Volume4
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Natriuresis
Aldosterone
Spironolactone
Heart Failure
Mineralocorticoid Receptor Antagonists
Sodium Potassium Chloride Symporter Inhibitors
Placebos
Therapeutics
Length of Stay
Safety
Natriuretic Peptides
Hyperkalemia
Random Allocation
Diuretics
Dyspnea
Infarction
Urine
Kidney
Weights and Measures

Keywords

  • acute heart failure
  • aldosterone
  • heart failure
  • hospitalization
  • mineralocorticoid receptor antagonist
  • natriuretic peptides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Rationale and Design of the ATHENA-HF Trial : Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure. / Butler, Javed; Hernandez, Adrian F.; Anstrom, Kevin J.; Kalogeropoulos, Andreas; Redfield, Margaret May; Konstam, Marvin A.; Tang, W. H Wilson; Felker, G. Michael; Shah, Monica R.; Braunwald, Eugene.

In: JACC: Heart Failure, Vol. 4, No. 9, 01.09.2016, p. 726-735.

Research output: Contribution to journalReview article

Butler, J, Hernandez, AF, Anstrom, KJ, Kalogeropoulos, A, Redfield, MM, Konstam, MA, Tang, WHW, Felker, GM, Shah, MR & Braunwald, E 2016, 'Rationale and Design of the ATHENA-HF Trial: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure', JACC: Heart Failure, vol. 4, no. 9, pp. 726-735. https://doi.org/10.1016/j.jchf.2016.06.003
Butler, Javed ; Hernandez, Adrian F. ; Anstrom, Kevin J. ; Kalogeropoulos, Andreas ; Redfield, Margaret May ; Konstam, Marvin A. ; Tang, W. H Wilson ; Felker, G. Michael ; Shah, Monica R. ; Braunwald, Eugene. / Rationale and Design of the ATHENA-HF Trial : Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure. In: JACC: Heart Failure. 2016 ; Vol. 4, No. 9. pp. 726-735.
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abstract = "Although therapy with mineralocorticoid receptor antagonists (MRAs) is recommended for patients with chronic heart failure (HF) with reduced ejection fraction and in post-infarction HF, it has not been studied well in acute HF (AHF) despite being commonly used in this setting. At high doses, MRA therapy in AHF may relieve congestion through its natriuretic properties and mitigate the effects of adverse neurohormonal activation associated with intravenous loop diuretics. The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) trial is a randomized, double-blind, placebo-controlled study of the safety and efficacy of 100 mg/day spironolactone versus placebo (or continued low-dose spironolactone use in participants who are already receiving spironolactone at baseline) in 360 patients hospitalized for AHF. Patients are randomized within 24 h of receiving the first dose of intravenous diuretics. The primary objective is to determine if high-dose spironolactone, compared with standard care, will lead to greater reductions in N-terminal pro−B-type natriuretic peptide levels from randomization to 96 h. The secondary endpoints include changes in the clinical congestion score, dyspnea relief, urine output, weight change, loop diuretic dose, and in-hospital worsening HF. Index hospital length of stay and 30-day clinical outcomes will be assessed. Safety endpoints include risk of hyperkalemia and renal function. Differences among patients with reduced versus preserved ejection fraction will be determined. (Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure [ATHENA-HF]; NCT02235077)",
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