A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: A randomized feasibility and safety study

Aims: Besides stimulating hematopoiesis, erythro-poietin (EPO) protects against experimental ischemic injury in the heart. The present study evaluated the safety and tolerability of EPO treatment in non-anemic patients with acute myocardial infarction (MI). Methods and Results: In this single-center, investigator-initiated, prospective study, patients with a first acute MI were randomized to one bolus of 300 mu g darbepoetin alfa or no additional medication before primary coronary intervention. Twenty-two patients (mean age 59 +/- 2 years) were included. In the darbepoetin group, serum EPO-levels increased to 130-270 times that of controls, within the first 24 h. After darbepoetin administration, only small and nonsignificant changes in hematocrit levels were observed, while endothelial progenitor cells (EPCs, CD34+/CD45-) were increased at 72 h (2.8 vs. 1.0 cells/mu l in control group,p < 0.01). No adverse events were recorded during the 30-day follow-up. After 4 months, left ventricular ejection fraction was similar in the two groups (52 +/- 3% in darbepoetin vs. 48 +/- 5% in control group, p = NS). Conclusions: Intravenous single high-dose darbepoetin alfa in acute MI is both safe and well tolerated. Darbepoetin treatment after MI stimulates EPCs mobilization. The results of this first pilot study support a larger scale clinical trial to establish efficacy of EPO administration in patients after acute MI.