Skip to main content

Main menu

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 articles
    • Obituary notices
  • Authors & Reviewers
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
    • Patient engagement
  • Physicians & Subscribers
    • Benefits for Canadian physicians
    • CPD Credits for CMA Members
    • Subscribe to CMAJ Print
    • Subscription prices
    • Obituary notices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2023
    • Avis de décès
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN

User menu

Search

  • Advanced search
CMAJ
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN
CMAJ

Advanced Search

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 articles
    • Obituary notices
  • Authors & Reviewers
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
    • Patient engagement
  • Physicians & Subscribers
    • Benefits for Canadian physicians
    • CPD Credits for CMA Members
    • Subscribe to CMAJ Print
    • Subscription prices
    • Obituary notices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2023
    • Avis de décès
  • Visit CMAJ on Facebook
  • Follow CMAJ on Twitter
  • Follow CMAJ on Pinterest
  • Follow CMAJ on Youtube
  • Follow CMAJ on Instagram
Practice

Aldosterone blockade after myocardial infarction

Daniel G. Hackam
CMAJ September 02, 2003 169 (5) 444;
Daniel G. Hackam
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Responses
  • Metrics
  • PDF
Loading

Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309-21.

Background: Patients presenting with acute myocardial infarction complicated by congestive heart failure are at particularly high risk of death and recurrent cardiovascular events.1 The use of spironolactone, a nonselective aldosterone inhibitor, led to impressive reductions in morbidity and mortality in a randomized trial involving patients with severe chronic heart failure.2 The effects of aldosterone blockade on morbidity and mortality after myocardial infarction are largely unknown.

Question: Does eplerenone, a novel selective aldosterone inhibitor, reduce rates of hospital admission and death from cardiovascular events among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure, who are receiving optimal medical therapy?

Design: In this randomized, double-blind trial, patients received either eplerenone (25 mg/d) or matching placebo for 4 weeks, after which the eplerenone dose was increased to a maximum of 50 mg/d. Aside from fulfilling standard criteria for acute myocardial infarction, patients were included if they had a left ventricular ejection fraction of 40% or lower and signs of congestive heart failure. Exclusion criteria were the use of potassium-sparing diuretics, a serum creatinine level of more than 220 μmol/L or a serum potassium concentration of more than 5.0 μmol/L at baseline.

The 2 primary end points were time to death from any cause, and time to death from cardiovascular causes or first hospital admission because of a cardiovascular event. Analyses were conducted according to the intention-to-treat principle.

Results: A total of 6642 patients were randomly assigned to receive eplerenone or placebo, with a mean follow-up of 16 months. The mean age at baseline was 64 years; 71% were men. The mean left ventricular ejection fraction was 33%. At baseline, most patients were receiving optimal medical therapy for acute myocardial infarction. The average dose of eplerenone in the treatment group was 43 mg. Loss to follow-up was less than 1%.

All-cause mortality was lower in the eplerenone group than in the placebo group (14.4% v. 16.7%; relative risk [RR] 0.85, 95% confidence interval [CI] 0.75–0.96). The rate of death from cardiovascular causes or hospital admissions because of cardiovascular events was also lower in the treatment group (26.7% v. 30.0%; RR 0.87, 95% CI 0.79–0.95). Broken down by cause, there was a statistically significant reduction in the rate of sudden cardiac death (RR 0.79, 95% CI 0.64–0.97); there were also reductions in the rates of death from acute myocardial infarction (RR 0.82, 95% CI 0.61–1.10) and death from heart failure (RR 0.80, 95% CI 0.62–1.04), although they did not reach statistical significance.

Serious hyperkalemia (defined as a serum potassium level ≥ 6.0 μmol/L) occurred in 5.5% of patients in the eplerenone group, as compared with 3.9% of patients in the placebo group (p = 0.002). However, the incidence of hypokalemia was significantly less common in the eplerenone group than in the placebo group (8.4% v. 13.1%; p < 0.001).

Commentary: This large, well-designed study shows that the addition of eplerenone to optimal medical therapy reduces the risk of death and readmission to hospital because of heart failure among patients with left ventricular dysfunction following myocardial infarction. It therefore confirms the importance of neurohumoral antagonism at the level of the aldosterone receptor first postulated by the RALES trial.2 Aldosterone, in addition to causing plasma volume expansion and impaired sodium excretion, is also a potent mediator of adverse vascular remodelling and myocardial interstitial fibrosis. Eplerenone has been shown to reduce vascular inflammation and myocardial fibrosis in animal models of cardiac disease, and to improve vascular compliance and endothelial dysfunction in older hypertensive patients.3,4

Practice implications: Patients with myocardial infarction should be treated optimally with an antiplatelet agent, statin, angiotensin-converting-enzyme inhibitor and β-blocker, with the addition of eplerenone for those who have congestive heart failure or left ventricular dysfunction, or both. The expected number needed to treat to save 1 life with 1 year of therapy is 50, with a number needed to treat of 33 to prevent 1 death from cardiovascular causes or 1 hospital admission because of a cardiovascular event in 1 year.

Daniel G. Hackam Fellow, Clinical Pharmacology University of Toronto Toronto, Ont.

References

  1. 1.↵
    Hellermann JP, Jacobsen SJ, Gersh BJ, Rodeheffer RJ, Reeder GS, Roger VL. Heart failure after myocardial infarction: a review. Am J Med 2002; 113 (4):324-30.
    OpenUrlCrossRefPubMed
  2. 2.↵
    Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341(10):709-17.
    OpenUrlCrossRefPubMed
  3. 3.↵
    Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002;283(5):H1802-10.
  4. 4.↵
    White WB, Duprez D, St Hillaire R, Krause S, Roniker B, Kuse-Hamilton J, et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003;41(5):1021-6.
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top

In this issue

Canadian Medical Association Journal: 169 (5)
CMAJ
Vol. 169, Issue 5
2 Sep 2003
  • Table of Contents
  • Index by author

Article tools

Respond to this article
Print
Download PDF
Article Alerts
To sign up for email alerts or to access your current email alerts, enter your email address below:
Email Article

Thank you for your interest in spreading the word on CMAJ.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Aldosterone blockade after myocardial infarction
(Your Name) has sent you a message from CMAJ
(Your Name) thought you would like to see the CMAJ web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Aldosterone blockade after myocardial infarction
Daniel G. Hackam
CMAJ Sep 2003, 169 (5) 444;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
‍ Request Permissions
Share
Aldosterone blockade after myocardial infarction
Daniel G. Hackam
CMAJ Sep 2003, 169 (5) 444;
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • References
  • Responses
  • Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

Practice

  • Vulvar condyloma lata as a first presentation of syphilis
  • Pregnancy in people living with obesity
  • Bedbugs
Show more Practice

In the Literature

  • Does the choice of β-blocker affect outcome in chronic heart failure?
  • Bisphosphonates and skeletal morbidity in patients with metastatic cancer
  • ACE inhibition in stable coronary artery disease
Show more In the Literature

Similar Articles

Collections

  • Topics
    • Cardiology: ischemic heart disease
    • Drugs: cardiovascular system

 

View Latest Classified Ads

Content

  • Current issue
  • Past issues
  • Collections
  • Sections
  • Blog
  • Podcasts
  • Alerts
  • RSS
  • Early releases

Information for

  • Advertisers
  • Authors
  • Reviewers
  • CMA Members
  • CPD credits
  • Media
  • Reprint requests
  • Subscribers

About

  • General Information
  • Journal staff
  • Editorial Board
  • Advisory Panels
  • Governance Council
  • Journal Oversight
  • Careers
  • Contact
  • Copyright and Permissions
CMAJ Group

Copyright 2023, CMA Impact Inc. or its licensors. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p)

All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association or its subsidiaries.

To receive any of these resources in an accessible format, please contact us at CMAJ Group, 500-1410 Blair Towers Place, Ottawa ON, K1J 9B9; p: 1-888-855-2555; e: cmajgroup@cmaj.ca

CMA Civility, Accessibility, Privacy

 

Powered by HighWire