A Single Dose of Erythropoietin in ST-Elevation Myocardial Infarction - HEBE III


The goal of the trial was to evaluate treatment with a single high dose of erythropoietin compared with control among patients who underwent reperfusion for ST-elevation myocardial infarction (STEMI).


Erythropoietin will be more effective in preventing complications of MI.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Patients who underwent successful primary PCI for STEMI

    Number of enrollees: 529
    Duration of follow-up: 6 weeks
    Age range: mean 61 years
    Percentage female: 22%


  • Anticipated revascularization within 6 weeks
  • Cardiogenic shock
  • End-stage renal disease
  • Uncontrolled hypertension
  • Previous treatment with erythropoietin

Primary Endpoints:

  • LVEF at 6 weeks

Secondary Endpoints:

  • Enzymatic infarct size
  • MACE

Drug/Procedures Used:

Within 3 hours of successful primary percutaneous coronary intervention (PCI), patients in The Netherlands were randomized to a single high dose of Epoetin Alfa 60,000 IU intravenously (n = 263) versus control (n = 266).

Concomitant Medications:

At enrollment, the use of aspirin was 95%, clopidogrel 86%, angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker 78%, beta-blocker 93%, and statins 97%.

Principal Findings:

Overall, 529 patients were randomized. In the total cohort, the mean age was 61 years, 22% were women, 9% had diabetes, mean hemoglobin was 14 g/dl, systolic blood pressure was 129 mm Hg, and mean heart rate was 75 bpm.

The primary outcome, left ventricular ejection fraction (LVEF) at 6 weeks, was 53% in the erythropoietin group versus 52% in the control group (p = 0.41).

Major adverse cardiac events (MACE) (cardiovascular death, MI, revascularization, stroke, or heart failure) were 3.0% in the erythropoietin group versus 7.1% in the control group (p = 0.031).

Change in hemoglobin was -0.52 g/dl in the erythropoietin group versus -0.55 g/dl in the control group (p = 0.86). There were no reports of malignant hypertension, seizure, or deep vein thrombosis.


Among patients who underwent successful primary PCI, a single high dose of erythropoietin was unable to increase LVEF at 6 weeks; however, the prespecified secondary outcome of MACE was reduced from this therapy. Follow-up hemoglobin levels were similar between groups, and there were no significant safety concerns from this exploratory study. A large phase 3 clinical trial will be needed to determine if erythropoietin can safely reduce clinical outcomes.


Voors AA, Belonje AM, Zijlstra F, et al.; on behalf of the HEBE III Investigators. A single dose of erythropoietin in ST-elevation myocardial infarction. Eur Heart J 2010;Aug 29:[Epub ahead of print].

Presented by Dr. Adriaan Voors at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Acute Heart Failure, Interventions and Vascular Medicine, Hypertension

Keywords: Seizures, Erythropoietin, Myocardial Infarction, Stroke, Follow-Up Studies, Heart Failure, Stroke Volume, Venous Thrombosis, Heart Rate, Angioplasty, Balloon, Coronary, Diabetes Mellitus, Hypertension, Malignant

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