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Drug Insight: aldosterone-receptor antagonists in heart failure—the journey continues

Nature Clinical Practice Cardiovascular Medicine volume 4, pages 368–378 (2007)Cite this article

Abstract

Aldosterone is an important mediator in the pathogenesis of heart failure, and increased plasma aldosterone levels are associated with a poor prognosis. Aldosterone-receptor blocking drugs can slow the progression of left ventricular remodeling and reduce the occurrence of sudden cardiac death. Two widely publicized clinical trials provide data demonstrating survival benefits with spironolactone and eplerenone in chronic and postinfarction heart failure. The publication of these trials has generated widespread enthusiasm for spironolactone and eplerenone, leading to the more frequent and sometimes unbridled use of these drugs in the medical community. We herein describe the likely mechanisms of action of aldosterone-receptor antagonists, discuss the existing clinical evidence supporting their use, and provide practical advice on their use in the management of patients with heart failure.

Key Points

  • Large clinical trials have shown aldosterone-receptor antagonists to be an effective treatment for patients with advanced symptomatic heart failure or postinfarction heart failure

  • Spironolactone and eplerenone have similar inhibitory effects on mineralocorticoid receptor activation, but cost and adverse effect profiles are different

  • Close monitoring of hyperkalemia and renal insufficiency are warranted to ensure the benefits of aldosterone-receptor antagonists outweigh the risks

  • Controversies still remain regarding the use of aldosterone-receptor antagonists in patients with mild symptoms or underlying diastolic heart failure, and the use of aldosterone-receptor antagonists in conjunction with angiotensin-converting-enzyme inhibitors, angiotensin-receptor antagonists and β-blockers

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Figure 1: The renin–angiotensin–aldosterone system
Figure 2: Kaplan–Meier analysis of the probability of survival among patients in the spironolactone-treated group and those in the placebo group from the Randomized Aldactone® Evaluation Study (RALES)
Figure 3: Kaplan–Meier estimates from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)

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Acknowledgements

Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. SR Kalidindi is a Clinical Scholar, WHW Tang is Assistant Professor of Medicine, and GS Francis is Professor of Medicine at the Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.,

    Srinivasa R Kalidindi, WH Wilson Tang & Gary S Francis

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Correspondence to Gary S Francis.

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Competing interests

WHW Tang serves as a consultant for AstraZeneca Pharmaceuticals. He receives research support from the American Heart Association and GlaxoSmithKline Pharmaceuticals.

Gary S Francis serves on Scientific Advisory Boards for Pfizer. He receives research grant support from Pfizer for conducting a mechanistic study using eplerenone. He also serves as a consultant to Novartis Pharmaceuticals.

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Kalidindi, S., Tang, W. & Francis, G. Drug Insight: aldosterone-receptor antagonists in heart failure—the journey continues. Nat Rev Cardiol 4, 368–378 (2007). https://doi.org/10.1038/ncpcardio0914

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