CLINICAL RESEARCH
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 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 aldosterone blocker eplerenone on mortality 30 days after randomization in patients after acute myocardial infarction (AMI) with a left ventricular ejection fraction (LVEF)  40% and clinical signs of heart failure.
BACKGROUND: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), eplerenone reduced all-cause mortality by 15% (p = 0.008) over a mean follow-up of 16 months when used with standard therapy in patients after AMI with an LVEF 40% and clinical signs of heart failure.
METHODS: We analyzed the effect of eplerenone 25 mg/day initiated 3 to 14 days after AMI (mean, 7.3 days) on the co-primary end points of time to death from any cause and the composite end point of time to death from cardiovascular (CV) causes or hospitalization for CV events, and the secondary end points of CV mortality, sudden cardiac death, and fatal/nonfatal hospitalization for heart failure, after 30 days of therapy in the EPHESUS trial.
RESULTS: At 30 days after randomization, eplerenone reduced the risk of all-cause mortality by 31% (3.2% vs. 4.6% in eplerenone and placebo-treated patients, respectively; p = 0.004) and reduced the 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 mortality by 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 mortality 30 days after randomization (when initiated at a mean of 7.3 days after AMI) in addition to conventional therapy in patients with an LVEF 40% and signs of heart failure. Based on its early survival benefit, eplerenone should be administered in the hospital after AMI.
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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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|
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51(4):
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117(5):
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|
|
|
|
|
|
|
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1205 - 1211.
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|
|
|
|
|
|
|
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November 1, 2007;
50(5):
919 - 925.
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[Full Text]
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|
|
|
|
|
|
|
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August 1, 2007;
50(2):
e28 - e55.
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|
|
|
|
|
|
|
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115(23):
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|
|
|
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June 12, 2007;
115(23):
2983 - 2989.
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|
|
|
|
|
|
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|
|
|
|
|
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|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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J. Am. Coll. Cardiol.,
September 5, 2006;
48(5):
e247 - e346.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Epstein, G. H. Williams, M. Weinberger, A. Lewin, S. Krause, R. Mukherjee, R. Patni, and B. Beckerman
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Clin. J. Am. Soc. Nephrol.,
September 1, 2006;
1(5):
940 - 951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al.
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Europace,
September 1, 2006;
8(9):
746 - 837.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A Howard, J. W. Cheng, M. A Crouch, V. J Colucci, J. S Kalus, S. A Spinler, and M. Munger
Drug Therapy Recommendations from the 2005 ACC/AHA Guidelines for Treatment of Chronic Heart Failure
Ann. Pharmacother.,
September 1, 2006;
40(9):
1607 - 1616.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Verhamme, G. Mosis, J. Dieleman, B. Stricker, and M. Sturkenboom
Spironolactone and risk of upper gastrointestinal events: population based case-control study
BMJ,
August 12, 2006;
333(7563):
330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bochud, J. Nussberger, P. Bovet, M. R. Maillard, R. C. Elston, F. Paccaud, C. Shamlaye, and M. Burnier
Plasma Aldosterone Is Independently Associated With the Metabolic Syndrome
Hypertension,
August 1, 2006;
48(2):
239 - 245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Anand, A. N Mooss, and S. M Mohiuddin
Review: Aldosterone Inhibition Reduces the Risk of Sudden Cardiac Death in Patients with Heart Failure
Journal of Renin-Angiotensin-Aldosterone System,
March 1, 2006;
7(1):
15 - 19.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. P Liu, A. Maggioni, and E. J Velazquez
Use of Valsartan in Post-Myocardial Infarction and Heart Failure Patients
Journal of Renin-Angiotensin-Aldosterone System,
March 1, 2006;
7(1_suppl):
S19 - S22.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. D Moyer and P. B Berger
Adjunctive treatment with eplerenone reduced 30 day all cause mortality in acute myocardial infarction
Evid. Based Med.,
February 1, 2006;
11(1):
14 - 14.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. S. Weintraub
Implications of the Multicenter Automatic Defibrillator Implantation Trial-II
Ann Intern Med,
January 3, 2006;
144(1):
65 - 65.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Pitt, the EPHESUS Investigators, F. Zijlstra, I. C.C. van der Horst, A. Khera, B. D. Levine, A. G. Jacobs, S. D. Solomon, R. M. Califf, M. A. Pfeffer, et al.
Sudden Death in Patients with Myocardial Infarction
N. Engl. J. Med.,
September 22, 2005;
353(12):
1294 - 1297.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Early Post-MI Mortality Benefit of Eplerenone in Selected Patients with LVSD
Journal Watch Cardiology,
September 9, 2005;
2005(909):
2 - 2.
[Full Text]
|
|
|
|
