Eplerenone Reduces Mortality 30 Days After Randomization Following Acute Myocardial Infarction in Patients With Left Ventricular Systolic Dysfunction and Heart Failure

doi:10.1016/j.jacc.2005.04.038

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J Am Coll Cardiol, 2005; 46:425-431, doi:10.1016/j.jacc.2005.04.038 (Published online 5 July 2005).
© 2005 by the American College of Cardiology Foundation

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CLINICAL RESEARCH: CLINICAL TRIAL

Eplerenone Reduces Mortality 30 Days After Randomization Following Acute Myocardial Infarction in Patients With Left Ventricular Systolic Dysfunction and Heart Failure

Bertram Pitt, MD, FACC^_*^,_*, Harvey White, DSc, FACC, Jose Nicolau, MD, FACC, Felipe Martinez, MD, Mihai Gheorghiade, MD, FACC^||, Michael Aschermann, MD^¶, Dirk J. van Veldhuisen, MD, FACC^#, Faiez Zannad, MD^_*_*, Henry Krum, MD, Robin Mukherjee, PhD, John Vincent, MD, PhD for the EPHESUS Investigators

^_* University of Michigan School of Medicine, Ann Arbor, Michigan
Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland, New Zealand
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Fundacion Rusculleda, Cárdoba, Argentina
^|| Northwestern University Medical School Feinberg School of Medicine, Chicago, Illinois
^¶ Interni Klinika, Cardiovascular Center, Prague, Czech Republic
^# University Hospital Groningen, Department of Cardiology, Groningen, the Netherlands
^_*_* Clinical Investigation Center INSERM-CHU de Nancy Hôpital Jeanne d’Arc, Dommartin-les Toul, Centre d’Investigation Clinique de Nancy, France
Monash University, Alfred Hospital, Melbourne, Australia
Pfizer Inc., New York, New York.

Manuscript received February 8, 2005; revised manuscript received March 28, 2005, accepted April 5, 2005.

^_* Reprint requests and correspondence: Dr. Bertram Pitt, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109. (Email: bpitt{at}med.umich.edu).

OBJECTIVES: This study sought to assess the impact of the selective aldosteroneblocker eplerenone on mortality 30 days after randomizationin patients after acute myocardial infarction (AMI) with a leftventricular ejection fraction (LVEF) $≤$ 40% and clinical signsof heart failure.

BACKGROUND: In the Eplerenone Post-Acute Myocardial Infarction Heart FailureEfficacy and Survival Study (EPHESUS), eplerenone reduced all-causemortality by 15% (p = 0.008) over a mean follow-up of 16 monthswhen used with standard therapy in patients after AMI with anLVEF $≤$ 40% and clinical signs of heart failure.

METHODS: We analyzed the effect of eplerenone 25 mg/day initiated 3 to14 days after AMI (mean, 7.3 days) on the co-primary end pointsof time to death from any cause and the composite end pointof time to death from cardiovascular (CV) causes or hospitalizationfor CV events, and the secondary end points of CV mortality,sudden cardiac death, and fatal/nonfatal hospitalization forheart failure, after 30 days of therapy in the EPHESUS trial.

RESULTS: At 30 days after randomization, eplerenone reduced the riskof all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone andplacebo-treated patients, respectively; p = 0.004) and reducedthe risk of CV mortality/CV hospitalization by 13% (8.6% vs.9.9% in eplerenone and placebo-treated patients, respectively;p = 0.074). Eplerenone also reduced the risk of CV mortalityby 32% (p = 0.003) and the risk of sudden cardiac death by 37%(p = 0.051).

CONCLUSIONS: Eplerenone 25 mg/day significantly reduced all-cause mortality30 days after randomization (when initiated at a mean of 7.3days after AMI) in addition to conventional therapy in patientswith an LVEF $≤$ 40% and signs of heart failure. Based on its earlysurvival benefit, eplerenone should be administered in the hospitalafter AMI.

Abbreviations and Acronyms
  ACE = angiotensin-converting enzyme
  AMI = acute myocardial infarction
  ARB = angiotensin receptor blocker
  CI = confidence interval
  CV = cardiovascular
  EPHESUS = Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study
  LVEF = left ventricular ejection fraction
  LVSD = left ventricular systolic dysfunction
  PIIINP = procollagen type III amino-terminal peptide

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