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

Cardiovasc Drugs Ther. 2006 Apr;20(2):135-41. doi: 10.1007/s10557-006-7680-5.

Abstract

Aims: Besides stimulating hematopoiesis, erythropoietin (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 microg 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 non-significant changes in hematocrit levels were observed, while endothelial progenitor cells (EPCs, CD34+/CD45-) were increased at 72 h (2.8 vs. 1.0 cells/microl 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon, Coronary / methods
  • Antigens, CD34 / analysis
  • Blood Cell Count / methods
  • Blood Platelets / cytology
  • Blood Platelets / drug effects
  • Darbepoetin alfa
  • Electrocardiography / drug effects
  • Electrocardiography / methods
  • Erythropoietin / analogs & derivatives*
  • Erythropoietin / blood
  • Erythropoietin / therapeutic use
  • Feasibility Studies
  • Heart Conduction System / drug effects
  • Hemoglobins / metabolism
  • Humans
  • Injections, Intravenous
  • Leukocyte Common Antigens / analysis
  • Male
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Patient Selection
  • Prospective Studies
  • Reticulocytes / cytology
  • Reticulocytes / drug effects
  • Tachycardia, Ventricular / chemically induced
  • Tachycardia, Ventricular / therapy
  • Treatment Outcome

Substances

  • Antigens, CD34
  • Hemoglobins
  • Erythropoietin
  • Darbepoetin alfa
  • Leukocyte Common Antigens