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Effect of erythropoietin as an adjunct to primary percutaneous coronary intervention: a randomised controlled clinical trial
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  1. Andrew J Ludman1,
  2. Derek M Yellon1,
  3. Jonathan Hasleton1,
  4. Cono Ariti2,
  5. Girish Ganesha Babu1,
  6. Edney Boston-Griffiths1,
  7. Vinod Venugopal1,
  8. Malcolm Walker3,
  9. Diana Holdright3,
  10. Howard Swanton3,
  11. Tom Crake3,
  12. David Brull3,
  13. James C Moon3,
  14. Rajesh Puranik4,
  15. Vivek Mutharangu4,
  16. Andrew Taylor4,
  17. Derek J Hausenloy1
  1. 1The Hatter Cardiovascular Institute, University College London, London, UK
  2. 2Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK
  3. 3The Heart Hospital, University College London Hospital, London, UK
  4. 4UCL Institute of Child Health, Great Ormond Street Hospital, London, UK
  1. Correspondence to Professor Derek M Yellon, The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK; hatter.institute{at}ucl.ac.uk

Abstract

Objective The acute administration of high-dose erythropoietin (EPO) on reperfusing ischaemic myocardium has been reported to halve myocardial infarct (MI) size in preclinical studies, but its effect in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) remains unknown. We investigated whether high-dose EPO administered as an adjunct to PPCI reduces MI size.

Design Double-blinded, randomised, placebo-controlled.

Setting Single tertiary cardiac centre.

Patients Fifty-one ST elevation myocardial infarction patients undergoing PPCI.

Interventions Patients were randomly assigned to receive either a single intravenous bolus of EPO (50 000 IU) prior to PPCI with a further bolus given 24 h later (n=26) or placebo (n=25).

Main outcome measures MI size measured by 24 h area under the curve troponin T and cardiac magnetic resonance imaging performed on day 2 and at 4 months.

Results EPO treatment failed to reduce MI size (troponin T area under the curve: 114.6±78 μg/ml EPO vs 100.8±68 μg/ml placebo; infarct mass by cardiac magnetic resonance: 33±16 g EPO vs 25±16 g placebo; both p>0.05). Unexpectedly, EPO treatment doubled the incidence of microvascular obstruction (82% EPO vs 47% placebo; p=0.02) and significantly increased indexed left ventricular (LV) end-diastolic volumes (84±10 ml/m2 EPO vs 73±13 ml/m2 placebo; p=0.003), indexed LV end-systolic volumes (41±9 ml/m2 EPO vs 35±11 ml/m2 placebo; p=0.035) and indexed myocardial mass (89±16 g/m2 EPO vs 79±11 g/m2 placebo; p=0.03). At 4 months, there were no significant differences between groups.

Conclusions High-dose EPO administered as an adjunct to PPCI failed to reduce MI size. In fact, EPO treatment was associated with an increased incidence of microvascular obstruction, LV dilatation and increased LV mass.

Clinical Trial Registration Information http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4058 Unique Identifier=Study ID 4058.

  • Erythropoietin
  • primary percutaneous coronary intervention
  • ST-elevation myocardial infarction
  • cardiac MRI
  • microvascular obstruction
  • MRI
  • coronary intervention
  • myocardial viability
  • reperfusion

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Footnotes

  • See Editorial, p 1537

  • Funding The work was supported by Roche Ltd. which kindly supplied the rhEPOβ (NeoRecormon), but it played no role in conception, conduct or analysis of this study. This work was undertaken at University College London Hospital/University College London which received a proportion of funding from the Department of Health's National Institute of Health Research Biomedical Research Centres funding scheme.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the University College London R&D department.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Linked Articles

  • Editorial
    Lionel H Opie
  • PostScript
    BMJ Publishing Group Ltd and British Cardiovascular Society