Intravenous Erythropoietin in Patients with ST-Segment

Elevation MI

-- Study performed by: Najjar et al -- Presented by: Jay Hall PA-SII, Ali Rahimi MD

JAMA, May 11 2011Vol 305, No. 18

Erythropoietin 165-amino acid glycoprotein hormone

produced by peritubular capillary endothelial cells in the kidney and liver

secretion is regulated by oxygen levels

Main function regulates RBC production through the CFU-E (colony forming unit) which is a RBC precursor

Exhibits pleiotropic effects including angiogenisis and protects vs. apoptosis

Receptors on cardiocytes Preclinical data showed cardio-protective roll, decreased infarct size, reduce

apoptotic cells and reduce cardiocyte loss

Goal of Study

To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with a STEMI

Design Prospective, randomized, double-blind placebo

controlled trial.

The REVEAL trial: 28 US sites between October 2006 – February 2010 included 222 patients with STEMI who underwent PCI as primary reperfusion strategy.

Patients were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo.

Design Inclusion: STEMI with thrombolysis in mycoardial

infarction, underwent successful PCI within 8 hours of ischemia.

Exclusion: h/o LV dysfunction (LVEF < 50%), MI, CABAG, revascularization of culprit aa.

Prevention of confounding infarct size

Epoetin alfa or saline placebo was administered within 4 hours after PCI

Restoration of flow to grade 2 or greater

Design Patient underwent cardiac magnetic

resonance imaging (CMR) to evaluate LV volume – ESV, EDV LV mass LV function – LVEF Contrast for infarct size

Endpoints

Primary Endpoints Territory of the infarct size

Secondary Endpoints LV remodeling (LV ESV, EDV, LVEF)

Safety Endpoints Vitals, HgB, Recitculocytes, Clinical events

Results Infarct size measured 2-6d and 12 +2 weeks

following medication administration did not differ between epoetin and placebo

In either unadjusted or adjusted (age, artery)

Infarct mass did not differ at either time point

LVEF, LVESV, LVEDV indexed to BSA did not differ at any point

LV Mass indexed to BSA was statistically significant (P < 0.05)

Results Subgroup analyses showed that age group

may modify epoetin effects on infarct size.

In patients older than 70 the infarct size was LARGER on all CMR exams after receiving epoetin alfa vs placebo

Results unchanged when adjusted for DM (which was the only significant difference between the groups)

Results

Participants receiving epoetin alfa had a higher incidence of adverse events Epo: 69/125 {55.2%; 95% CI, 46.05-64.10%} Plac: 40/97 {41.2%; 95% CI, 31.33%-51.69%} P=.04

Also higher incident of serious adverse event 20.0%; 95% CI, [13.38-28.09%] vs. Placebo 10.3%;

95% CI [5.06-18.14%] P=.05

Results Of the 125 patients who received epoetin alfa,

5 experienced death, MI, stroke or stent thrombosis vs. 0 in 97 placebo patients

4.0% [95% CI, 1.31-9.09%] P=.04

Conclusion

A single bolus of 60,000 U of epoetin alfa in patients with STEMI given within 4 hours of PCI does not reduce infarct size and is related with higher adverse cardiac events

Furthermore it was shown to increase infarct size in patients aged 70 and older.

Level of Evidence