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


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.
Lipsic
Erik
E
Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands. e.lipsic@med.umcg.nl
van der Meer
Peter
P
Voors
Adriaan A
AA
Westenbrink
B Daan
BD
van den Heuvel
Ad F M
AF
de Boer
Hetty C
HC
van Zonneveld
Anton J
AJ
Schoemaker
Regien G
RG
van Gilst
Wiek H
WH
Zijlstra
Felix
F
van Veldhuisen
Dirk J
DJ
D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D018952:Antigens, CD34 / Q000032:analysis; D001772:Blood Cell Count / Q000379:methods; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D000068256:Darbepoetin alfa; D004562:Electrocardiography / Q000187:drug effects / Q000379:methods; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D005240:Feasibility Studies; D006329:Heart Conduction System / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018579:Patient Selection; D011446:Prospective Studies; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000628:therapy; D016896:Treatment Outcome
D018952:Antigens, CD34; D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D017493:Leukocyte Common Antigens