Effects of recombinant human erythropoietin on platelet activation in acute myocardial infarction: results of a double-blind, placebo-controlled, randomized trial

Abstract

Background: Erythropoietin mitigates myocardial damage and improves ventricular performance after experimental ischemic injury. This study assessed safety and efficacy markers relevant to the biological activity of recombinant human erythropoietin (rHuEpo) in patients with acute myocardial infarction (MI).

Methods: We conducted a prospective, placebo-controlled, randomized, double-blind trial to determine the effects of intravenous rHuEpo (200 U/kg daily for 3 consecutive days) on measures of platelet and endothelial cell activation, soluble Fas ligand, and peripheral blood mononuclear cell (PBMC) expression of angiogenesis signaling proteins in 44 subjects with acute MI treated with aspirin and clopidogrel after successful percutaneous coronary intervention.

Results: Recombinant human erythropoietin did not alter bleeding time, platelet function assay closure time, von Willebrand factor levels, soluble P-selectin, or soluble Fas ligand levels when compared with placebo. By contrast, rHuEpo significantly increased expression of erythropoietin receptor, vascular endothelial growth factor receptor Flt-1, and phosphorylated phosphatidylinositol 3-kinase in PBMCs when compared with placebo (all Ps < .05).

Conclusions: In acute MI patients treated with aspirin and clopidogrel, short-term administration of rHuEpo did not alter markers of platelet and endothelial cell activation associated with thrombosis, yet did increase expression of angiogenesis signaling proteins in PBMCs when compared with placebo. These data provide preliminary evidence of safety and biologic activity of rHuEpo at this dosing and support continued enrollment in ongoing efficacy trials.

Trial registration: ClinicalTrials.gov NCT00367991.

Conflict of interest statement

Conflict of Interest Disclosures

Dr. Katz has received consulting fees from Amgen, Inc. No other author reports any financial or other conflicts of interest.

Figures

Figure 1

Summary of study screening, most common criteria for exclusion, study enrollment, randomization and study drug allocation, and reasons for withdrawal from study. Legend CP-PCI=Time elapsed between onset of chest pain and percutaneous coronary intervention; HD=Hemodynamically; PCI-Screen=Time elapsed between percutaneous coronary intervention and study screening.