• End-systolic volume, end-diastolic volume, ejection fraction [ Time Frame: within 2-6 days of administration of study medication, and 3 months later ] [ Designated as safety issue: No ]
• Number of circulating endothelial progenitor cells [ Time Frame: within 2-6 days of administration of study medication, and 3 months later ] [ Designated as safety issue: No ]
• Changes in infarct size [ Time Frame: 3 months after administration of study medication ] [ Designated as safety issue: No ]
• Changes in hemoglobin levels [ Time Frame: during the first two weeks following study medication administration ] [ Designated as safety issue: Yes ]
• Occurrence of death or arterial or venous thrombotic events [ Time Frame: within 4 weeks following administration of study medication ] [ Designated as safety issue: Yes ]

• Changes in: infarct size 3 months after administration of study medication
• End-systolic volume, end-diastolic volume, ejection fraction within 2-6 days of administration of study medication, and at 3 months
• Number of circulating endothelial progenitor cells

The purpose of this study is to evaluate whether erythropoietin can help limit the damage to the heart in patients with acute heart attacks.

REVEAL is a randomized, double-blinded, placebo-controlled, parallel phase II clinical study that will evaluate the effects of erythropoietin administration on infarct size, left ventricular remodeling and circulating endothelial progenitor cells in patients with large myocardial infarctions (MI). The study will be conducted in two phases: a dose-escalation safety phase and a single dose efficacy phase. Eligible patients who present to the hospital with an acute ST-elevation MI and who agree to participate in this study will be randomly assigned to receive a single infusion of study medication consisting either of erythropoietin or placebo. The size of the infarction and the dimensions of the heart will be assessed by cardiac magnetic resonance imaging (MRI) within 2-6 days of the infusion of the study medication, and again approximately 3 months later.

• Drug: Erythropoietin (Epoetin alfa)
• Drug: Placebo

• Experimental: 15,000 Units
• Experimental: 30,000 Units
• Experimental: 60,000 Units

• Maiese K, Li F, Chong ZZ. New avenues of exploration for erythropoietin. JAMA. 2005 Jan 5;293(1):90-5. Review.
• Bogoyevitch MA. An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res. 2004 Aug 1;63(2):208-16. Review.
• Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, Thompson RB, Petrofski JA, Annex BH, Stamler JS, Koch WJ. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest. 2003 Oct;112(7):999-1007.
• Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, Lakatta EG, Talan MI. Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11612-7. Epub 2003 Sep 19.
• Moon C, Krawczyk M, Paik D, Lakatta EG, Talan MI. Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window. Cardiovasc Drugs Ther. 2005 Aug;19(4):243-50.

Inclusion Criteria:

• Age > 21 years
• Acute ST-elevation myocardial infarction
• Referral for primary or rescue angioplasty
• Revascularization procedure within 8 hours from the onset of ischemic symptoms
• TIMI (Thrombolysis in myocardial infarction) flow grade 0 or 1 in the culprit coronary artery at the beginning of coronary angiography
• Successful revascularization of infarct-related artery

Exclusion Criteria:

• Clinical indication for erythropoietin
• STEMI (ST-elevation myocardial infarction) due to occlusion of a branch vessel
• Any history of prior MI, PCI (Percutaneous coronary intervention), CABG (Coronary artery bypass graft), cardiomyopathy, myocarditis, or CHF (congestive heart failure)
• Hypersensitivity to human albumin, mammalian cell-derived products, or erythropoietin
• Hematocrit > 42% in men or > 40% in women at the time of study drug administration
• Uncontrolled hypertension at the time of study drug administration
• Cardiogenic shock
• Need for coronary surgical revascularization as determined at the time of the index coronary catheterization
• History of hypercoagulable disorder, thromboembolic event, or venous thrombosis
• History of stroke or TIA (transient ischemic attack)
• History of seizures
• Contraindication to MRI
• Pregnancy or nursing mother