Abstract 2012: Randomized Trial of Recombinant Human Erythropoietin in Patients with Acute Myocardial Infarction
Erythropoietin (EPO) is a glycoprotein growth factor that mitigates myocardial damage after experimental ischemic injury, but its clinical application in acute coronary syndromes is potentially limited by pro-thrombotic side effects. We hypothesized that clinically-indicated anti-platelet therapy after percutaneous coronary intervention (PCI) would mitigate pro-thrombotic effects of EPO and enhance its risk/benefit ratio in acute coronary syndrome. We conducted a prospective randomized double-blind trial to compare the effects of intravenous EPO (200 U/kg daily for 3 consecutive days) vs. matching placebo on measures of platelet and endothelial cell activation, echocardiogram-derived post-infarction left ventricular size and function, and peripheral blood mononuclear cell (PBMC) expression of angiogenic proteins in 44 subjects with acute myocardial infarction (MI) who were treated with aspirin and clopidogrel after successful PCI. Baseline clinical characteristics did not differ between groups. EPO did not alter bleeding time, platelet function assay closure time, von Willebrand factor levels, or P-selectin levels when compared with placebo. At 3 days post MI, EPO significantly increased expression of EPO receptor, vascular endothelial growth factor receptor Flt-1, and phosphorylated phosphatidylinositol 3-kinase in PBMC’s when compared with placebo. At 10 days post MI, EPO significantly reduced left ventricular end-diastolic volume (−7.7 ml (95% CI −10.5, −5.2), p<0.001) and end-systolic volume (−6.4 ml (95% CI −8.8, −4.2), p<0.001), and significantly increased left ventricular ejection fraction (+3.3%, (95% CI +1.9, +4.7), p<0.001) when compared with placebo. In patients with acute MI treated with aspirin and clopidogrel, short-term administration of high dose EPO did not alter surrogate markers of platelet and endothelial cell activation when compared with placebo. EPO was associated with evidence of improved early post-MI left ventricular function and increased expression of angiogenesis signaling proteins in PBMC’s when compared with placebo. Further studies are warranted to more fully characterize the therapeutic potential of EPO in this population.
This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).