Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction - REVEAL

May 11, 2011
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
National Institutes of Aging
Date Published:
01/01/2011
Date Updated:
05/11/2011
Original Posted Date:
05/11/2011
References

Description:

The goal of the trial was to evaluate treatment with erythropoietin compared with placebo after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).

Hypothesis:

Erythropoietin will reduce infarction size.

Study Design

  • Blinded
  • Placebo Controlled
  • Randomized
  • Stratified

Patient Populations:

  • Patients with STEMI, <8 hours from symptom onset

    Number of screened applicants: 3,759
    Number of enrollees: 222
    Duration of follow-up: 12 weeks
    Mean patient age: 57 years
    Percentage female: 19%
    Ejection fraction: 48%

Exclusions:

  • Pre-existing left ventricular dysfunction
  • History of MI
  • History of coronary artery bypass grafting or PCI in the territory of the culprit artery

Primary Endpoints:

  • Infarct size as a percentage of left ventricular mass

Secondary Endpoints:

  • Clinical outcomes

Drug/Procedures Used:

STEMI patients were randomized to intravenous epoetin alfa 60,000 U (n = 68) versus placebo (n = 70) in the primary efficacy analysis. An additional cohort of patients received epoetin alfa 15,000 U and 30,000 U to assess safety.

Cardiac magnetic resonance (CMR) was initially performed 2-6 days after study medication and again at 12 weeks.

Concomitant Medications:

At baseline in the epoetin alfa group, the use of aspirin was 89%, clopidogrel 96%, heparin 88%, and glycoprotein IIb/IIIa inhibitor 72%.

Principal Findings:

Overall, 222 STEMI patients were randomized (138 patients in efficacy analysis). In the epoetin alfa group, the mean age was 57 years (16% were ≥70 years), 19% were women, 11% had diabetes, infarct-related artery was the nonanterior location in 72%, and mean blood pressure was 130/78 mm Hg.

The primary outcome, infarct size (as a percentage of left ventricular mass) at first CMR was 15.8% in the epoetin alfa group versus 15.0% in the placebo group (p = 0.67). Among patients ≥70 years old, infarct size was 19.9% versus 11.7% (p = 0.03). At the second CMR, infarct size was 10.6% versus 10.4% (p = 0.89), respectively.

In the total cohort, death, MI, stroke, or stent thrombosis occurred in 4.0% versus 0% (p = 0.04), respectively.

Interpretation:

Among patients with STEMI who underwent reperfusion by PCI, the use of intravenous epoetin alfa was not beneficial. This medication did not reduce infarct size on either the initial CMR or a later CMR performed at 12 weeks. In fact, infarct size was larger in a prespecified cohort of patients ≥70 years old. Clinical outcomes of death, MI, stroke, or stent thrombosis were also more frequent in the epoetin alfa group. The use of erythropoietin should likely be avoided in acute coronary syndromes.

References:

Najjar SS, Rao SV, Melloni C, et al. Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction. REVEAL: a randomized controlled trial. JAMA 2011;305:1863-72.

Keywords: Erythropoietin, Myocardial Infarction, Acute Coronary Syndrome, Stroke, Thrombosis, Recombinant Proteins, Blood Pressure, Magnetic Resonance Spectroscopy, Diabetes Mellitus, Stents, Percutaneous Coronary Intervention


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