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 Vol 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 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, %}  Plac: 40/97 {41.2%; 95% CI, 31.33%-51.69%} P=.04  Also higher incident of serious adverse event  20.0%; 95% CI, [ %] vs. Placebo 10.3%; 95% CI [ %] 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, %] 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