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Canadian Journal of Cardiology

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

Published:February 07, 2019DOI:https://doi.org/10.1016/j.cjca.2019.01.022

      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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      Linked Article

      • Cardiorenal Interactions, Diuretic Resistance, and Acute Heart Failure: Renal Response vs Renal Function
        Canadian Journal of CardiologyVol. 35Issue 9
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          The 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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