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
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