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

• Published in: Cardiovascular drugs and therapy 2006-04, Vol.20 (2), p.135-141
• Main Authors: LIPSIC, Erik, VAN DER MEER, Peter, VAN VELDHUISEN, Dirk J, VOORS, Adriaan A, DAAN WESTENBRINK, B, VAN DEN HEUVEL, Ad F. M, DE BOER, Hetty C, VAN ZONNEVELD, Anton J, SCHOEMAKER, Regien G, VAN GILST, Wiek H, ZIJLSTRA, Felix
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon, Coronary - methods; Antigens, CD34 - analysis; Biological and medical sciences; Blood Cell Count - methods; Blood Platelets - cytology; Blood Platelets - drug effects; Cardiology. Vascular system; Cardiovascular system; Coronary heart disease; Darbepoetin alfa; Electrocardiography - drug effects; Electrocardiography - methods; Erythropoietin - analogs & derivatives; Erythropoietin - blood; Erythropoietin - therapeutic use; Feasibility Studies; Heart; Heart Conduction System - drug effects; Hemoglobins - metabolism; Humans; Injections, Intravenous; Leukocyte Common Antigens - analysis; Male; Medical sciences; Mesenchymal Stromal Cells - chemistry; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Middle Aged; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocarditis. Cardiomyopathies; Patient Selection; Pharmacology. Drug treatments; Prospective Studies; Reticulocytes - cytology; Reticulocytes - drug effects; Tachycardia, Ventricular - chemically induced; Tachycardia, Ventricular - therapy; Treatment Outcome
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-006-7680-5

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). 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). 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.