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.
Résumé
Contexte
Les patients présentant une insuffisance cardiaque (IC) aiguë accompagnée d’une insuffisance
rénale et de facteurs de risque de résistance aux diurétiques pourraient être plus
susceptibles d’obtenir une réduction significative de la congestion grâce à l’ajout
de spironolactone.
Méthodologie
L’essai ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) a été mené auprès de 360 patients présentant une IC aiguë et une fraction d’éjection
réduite ou préservée, répartis aléatoirement pour recevoir pendant 96 heures soit
de la spironolactone à raison de 100 mg par jour, soit les soins usuels. La présente
analyse visait à évaluer les effets du traitement à l’étude en fonction des tertiles
du taux de filtration glomérulaire estimé (TFGe) au début de l’étude et des sous-groupes
de sujets présentant un risque accru de résistance aux diurétiques.
Résultats
Dans tous les tertiles du TFGe, l’administration d’une forte dose de spironolactone
n’a procuré aucun bienfait supplémentaire à l’égard des paramètres d’efficacité, y
compris les variations logarithmiques du fragment N-terminal du propeptide du peptide
natriurétique de type B N-Terminal et les signes et symptômes de congestion (toutes
les valeurs de p pour l’interaction ≥ 0,06). L’administration d’une forte dose de spironolactone n’a
pas eu d’effet significatif quant à la réduction du propeptide natriurétique de type
B N-terminal, sans égard à la pression artérielle, à la présence ou à l’absence de
diabète et à la dose du diurétique de l’anse (toutes les valeurs de p pour l’interaction ≥ 0,38). Les variations des taux sériques de potassium et de créatinine
durant l’hospitalisation étaient comparables dans les deux groupes de traitement,
et ce, dans tous les tertiles du TFGe (toutes les valeurs de p pour l’interaction ≥ 0,18). Le taux de patients dont l’IC s’est aggravée durant l’hospitalisation
et après 30 jours, ainsi que le taux de mortalité toutes causes confondues à 60 jours,
étaient numériquement supérieurs chez les patients présentant un TFGe inférieur au
départ, mais les effets relatifs du traitement à l’étude ne variaient pas selon l’état
de la fonction rénale (toutes les valeurs de p pour l’interaction ≥ 0,27).
Conclusions
L’administration d’une forte dose de spironolactone ne s’est pas révélée supérieure
aux soins usuels pour réduire la congestion chez les patients présentant une IC aiguë,
indépendamment de l’état de leur fonction rénale et des facteurs de risque de résistance
aux diurétiques présents. La mise en route ou la poursuite du traitement par la spironolactone
chez les patients hospitalisés s’est révélée sans danger durant le séjour à l’hôpital,
même lorsque le médicament était administré à de fortes doses à des patients présentant
une dysfonction rénale modérée.
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Article info
Publication history
Published online: February 07, 2019
Accepted:
January 28,
2019
Received:
November 20,
2018
Footnotes
See editorial by Clarke, pages 1079–1081 of this issue.
Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02235077.
See page 1104 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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- Cardiorenal Interactions, Diuretic Resistance, and Acute Heart Failure: Renal Response vs Renal FunctionCanadian Journal of CardiologyVol. 35Issue 9
- PreviewThe cornerstone of treatment for acute heart failure, irrespective of left ventricular ejection fraction, is diuresis to relieve pulmonary or peripheral edema (“decongestive therapy”). Intravenous loop diuretics are the standard of care in this situation, with clinical trials of novel therapies failing to demonstrate a meaningful benefit as adjunctive treatment strategies.1-4 Ultrafiltration can improve congestive symptoms more quickly, but there is limited evidence to support its use as first-line therapy over diuretics.
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