Intracoronary administration of darbepoetin-alpha at onset of reperfusion in acute myocardial infarction: results of the randomized Intra-Co-EpoMI trial

Arch Cardiovasc Dis. 2013 Mar;106(3):135-45. doi: 10.1016/j.acvd.2012.12.001. Epub 2013 Feb 1.

Abstract

Background: Several trials investigating erythropoietin as a novel cytoprotective agent in myocardial infarction (MI) failed to translate promising preclinical results into the clinical setting. These trials could have missed crucial events occurring in the first few minutes of reperfusion. Our study differs by earlier intracoronary administration of a longer-acting erythropoietin analogue at the onset of reperfusion.

Aim: To evaluate the ability of intracoronary administration of darbepoetin-alpha (DA) at the very onset of the reperfusion, to decrease infarct size (IS).

Methods: We randomly assigned 56 patients with acute ST-segment elevation MI to receive an intracoronary bolus of DA 150 μg (DA group) or normal saline (control group) at the onset of reflow obtained by primary percutaneous coronary intervention (PCI). IS and area at risk (AAR) were evaluated by biomarkers, cardiac magnetic resonance (CMR) and validated angiographical scores.

Results: There was no difference between groups regarding duration of ischemia, Thrombolysis in Myocardial Infarction flow grade at admission and after PCI, AAR size and extent of the collateral circulation, which are the main determinants of IS. The release of creatine kinase was not significantly different between the two groups even when adjusted to AAR size. Between 3-7 days and at 3 months, the area of hyperenhancement on CMR expressed as a percentage of the left ventricular myocardium was not significantly reduced in the DA group even when adjusted to AAR size.

Conclusion: Early intracoronary administration of a longer-acting erythropoietin analogue in patients with acute MI at the time of reperfusion does not significantly reduce IS.

Trial registration: ClinicalTrials.gov NCT01043991.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Collateral Circulation
  • Coronary Angiography
  • Coronary Circulation
  • Creatine Kinase / blood
  • Darbepoetin alfa
  • Drug Administration Schedule
  • Erythropoietin / administration & dosage
  • Erythropoietin / adverse effects
  • Erythropoietin / analogs & derivatives*
  • Female
  • France
  • Humans
  • Injections, Intra-Arterial
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / diagnosis
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Percutaneous Coronary Intervention* / adverse effects
  • Predictive Value of Tests
  • Prospective Studies
  • Single-Blind Method
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Erythropoietin
  • Darbepoetin alfa
  • Creatine Kinase

Associated data

  • ClinicalTrials.gov/NCT01043991