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Randomized Controlled Trial
. 2019 Sep;35(9):1097-1105.
doi: 10.1016/j.cjca.2019.01.022. Epub 2019 Feb 7.

Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial

Stephen J Greene  1 , G Michael Felker  2 , Anna Giczewska  3 , Andreas P Kalogeropoulos  4 , Andrew P Ambrosy  5 , Hrishikesh Chakraborty  6 , Adam D DeVore  2 , Marat Fudim  2 , Steven E McNulty  6 , Robert J Mentz  2 , Muthiah Vaduganathan  7 , Adrian F Hernandez  2 , Javed Butler  8
Affiliations
Randomized Controlled Trial

Spironolactone in Acute Heart Failure Patients With Renal Dysfunction and Risk Factors for Diuretic Resistance: From the ATHENA-HF Trial

Stephen J Greene et al. Can J Cardiol. 2019 Sep.

Abstract

Background: Acute heart failure (HF) patients with renal insufficiency and risk factors for diuretic resistance may be most likely to derive incremental improvement in congestion with the addition of spironolactone.

Methods: The Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) trial randomized 360 acute HF patients with reduced or preserved ejection fraction to spironolactone 100 mg daily or usual care for 96 hours. The current analysis assessed the effects of study therapy within tertiles of baseline estimated glomerular filtration rate (eGFR) and subgroups at heightened risk for diuretic resistance.

Results: Across eGFR tertiles, there was no incremental benefit of high-dose spironolactone on any efficacy endpoint, including changes in log N-terminal pro-B-type natriuretic peptide and signs and symptoms of congestion (all P for interaction ≥ 0.06). High-dose spironolactone had no significant effect on N-terminal pro-B-type natriuretic peptide reduction regardless of blood pressure, diabetes mellitus status, and loop diuretic dose (all P for interaction ≥ 0.38). In-hospital changes in serum potassium and creatinine were similar between treatment groups for all GFR tertiles (all P for interaction ≥ 0.18). Rates of inpatient worsening HF, 30-day worsening HF, and 60-day all-cause mortality were numerically higher among patients with lower baseline eGFR, but relative effects of study treatment did not differ with renal function (all P for interaction ≥ 0.27).

Conclusions: High-dose spironolactone did not improve congestion over usual care among patients with acute HF, irrespective of renal function and risk factors for diuretic resistance. In-hospital initiation or continuation of spironolactone was safe during the inpatient stay, even when administered at high doses to patients with moderate renal dysfunction.

Trial registration: ClinicalTrials.gov NCT02235077.

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Figures

Figure 1.
Figure 1.. Forest plot of pre-specified subgroup analyses.
Median SBP was 122 mmHg and median daily furosemide equivalent dose was 80 mg. X-axis represents treatment difference for change in log NT-proBNP. GFR, estimated glomerular filtration rate; NT-proBNP, N-terminal pro-B-type natriuretic peptide; SBP, systolic blood pressure
See this image and copyright information in PMC

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References

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