Effectiveness of Aldosterone Antagonist Therapy Use Among Older Patients After Acute Myocardial Infarction

Sandi Harris, Mercer University College of Pharmacy


The American College of Cardiology/American Heart Association 2013 heart failure guidelines recommend the use of aldosterone receptor antagonists to reduce morbidity and mortality following an acute myocardial infarction in patients who have left ventricular ejection fraction of 40% or less. [1]


The eplerenone post-acute myocardial infarction heart failure efficacy and survival

study (EPHESUS) trial, upon which the recommendation is based, showed a 15% mortality benefit with the addition of an aldosterone receptor antagonist. [2]


Title: Effectiveness and Safety of Aldosterone Antagonist Therapy Use Among Older Patients With Reduced Ejection Fraction After Acute Myocardial Infarction
Design Retrospective cohort study (N= 12,080)
Objective To describe current patterns of aldosterone antagonist use in routine practice, and to assess the longitudinal effectiveness and safety of aldosterone antagonists among an older myocardial infarction (MI) patient population
Study Groups Patients who met a guideline indication for aldosterone antagonist therapy, defined as in‐hospital ejection fraction ≤40% and either: (1) signs or symptoms of heart failure (HF) on admission or during the index MI hospitalization, or (2) in the absence of HF, a history of diabetes was present. The patients were then divided in two groups: patients receiving a prescription for either spironolactone or epleronone (n= 1,310) and those patients not prescribed an aldosterone antagonist (n= 10,770).
Methods Baseline clinical characteristics and in‐hospital treatment were compared between patients who were and were not discharged on aldosterone antagonist therapy. Continuous variables were expressed as median values with 25th and 75th percentiles, and categorical variables were presented as percentages.

The unadjusted cumulative incidence of each outcome was compared using log‐rank tests for mortality

Duration January 1, 2007 and December 31, 2010
Primary Outcome Measure  Difference in two year mortality between the group of patients prescribed an aldosterone antagonist and those who did not receive an aldosterone antagonist
Baseline Characteristics Aldosterone Antagonist at Discharge Prescribed

(n= 1,310)

Not Prescribed (n= 10,770)
Average Age, y 76 77
Female sex 45.0% 44.0%
White 86.8% 86.8%
Black 7.7% 7.8%
Other 5.5% 5.4%
Prior Heart Failure 40.0% 31.8%
Prior Myocardial Infarction 38.2% 35.9%
Prior Coronary Artery Bypass Graft 25.6% 25.8%
Prior Percutaneous Intervention 27.9% 27.2%
Results Risk‐adjusted mortality between patients treated with and without aldosterone antagonists: adjusted HR 0.99, 95% CI 0.88 to 1.13.
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Aldosterone antagonist use among eligible older MI patients in routine clinical practice was not associated with lower mortality except in patients with HF symptoms, but was associated with increased risks of hyperkalemia and acute renal failure.


This study failed to replicate the primary outcomes of mortality benefit seen in the EPHESUS trial. The average age of patients included in the trial was older and comorbidities were not excluded.


The mortality benefit of adding an aldosterone antagonist may not outweigh the risks in all patient populations.



  1. Yancy CW,et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239.
  2. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309-21.
  3. Wang TY, Vora AN, Peng SA, et al. Effectiveness and Safety of Aldosterone Antagonist Therapy Use Among Older Patients With Reduced Ejection Fraction After Acute Myocardial Infarction. J Am Heart Assoc. 2016;5(1):e002612.


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