Effects of Recombinant Human Erythropoietin on Platelet Function in Patients With Acute Myocardial Infarction

• Bleeding Time [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: Yes ]
  An integrated measure of in vivo platelet function and tissue hemostasis
• Platelet Function Assay Closure Time [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: Yes ]

• Bleeding time
• Platelet function assay closure time

• Left Ventricular Ejection Fraction [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
• Serum Markers of Myocyte Damage and Apoptosis [ Time Frame: Day 1 and Day 10 ] [ Designated as safety issue: No ]
• Circulating Endothelial Progenitor Cells [ Time Frame: Day 3 and Day 10 ] [ Designated as safety issue: No ]

• Left ventricular ejection fraction
• Serum markers of myocyte damage and apoptosis
• Circulating endothelial progenitor cells

The purpose of this study is to see if a naturally-occurring hormone called erythropoietin changes the action of platelets in the blood. Patients with heart attacks are treated with medicines to reduce the clotting action of platelets. This study is trying to determine whether erythropoietin alters the clotting action of platelets in patients receiving anti-platelet medicines. It is important to understand the effects of erythropoietin on platelets since preliminary studies in animals suggest that erythropoietin may protect the heart from damage during a heart attack.

Anti-apoptotic effects of erythropoietin in experimental myocardial infarction (MI) and ischemia-reperfusion injury suggest potential for therapeutic benefit in patients with acute MI. Before the therapeutic potential of recombinant human erythropoietin (rHuEpo) in acute MI can be tested in large clinical trials, more information on the effects of short-term rHuEpo on platelet function are needed. Accordingly, the current proposal aims to determine the effects of rHuEpo (at a dose previously shown not to inhibit the anti-platelet effects of aspirin and clopidogrel in healthy subjects) on platelet function and other safety measures and measure of infarct size in patients with acute coronary syndromes receiving clinically-indicated standard anti-platelet therapy with aspirin, clopidogrel and glycoprotein Iib-IIIa inhibitors.

Specific Aim 1: To determine the effects of intravenous rHuEpo 400 U/kg daily for 3 days vs. placebo on in vivo and in vitro platelet function in patients with acute MI undergoing percutaneous revascularization.

Specific Aim 2: To obtain pilot data to estimate the effects of administration of rHuEpo 400 U/kg daily for 3 days vs. placebo on biochemical markers of myocardial infarction size and left ventricular ejection fraction in patients with acute MI undergoing percutaneous revascularization

• Drug: Recombinant human erythropoietin alfa (drug)
  200 U/kg IV daily for 3 days vs. matched volume of normal saline IV daily for 3 days
• Drug: Placebo
  Normal saline to match active drug (rHuEpo)

• Active Comparator: A
  recombinant human erythropoietin 200 U/kg IV daily for 3 days
  Intervention: Drug: Recombinant human erythropoietin alfa (drug)
• Placebo Comparator: B
  Normal saline volume to match active treatment IV daily for 3 days
  Intervention: Drug: Placebo

Inclusion Criteria:

• Age 21-75 years
• Clinical evidence of acute myocardial infarction (MI) with total or sub-total occlusion on angiogram
• Status post percutaneous revascularization procedure for acute MI with TIMI 3 flow
• Ongoing clinically-indicated treatment with aspirin, thienopyridines

Exclusion Criteria:

• Hemodynamic instability/shock or severe congestive heart failure
• Time from onset of chest pain to revascularization procedure > 16 hours
• Use of intravenous thrombolytic agents for treatment of MI
• Known need for additional revascularization procedures