Lack of erythropoietin benefit in MI REVEALed
MedWire News: The REVEAL trial has failed to show a benefit from erythropoietin in the treatment of ST-segment elevation MI (STEMI), investigators report.
Contrary to previous evidence from animal studies, erythropoietin did not reduce infarct size - and was actually associated with a higher rate of cardiovascular (CV) events.
REVEAL (Reduction of Infarct Expansion and Ventricular Remodeling with Erythropoietin After Large Myocardial Infarction) was a prospective, randomized, double-blind, placebo-controlled trial conducted between October 2006 and February 2010, which included 222 patients who were recruited across 28 US sites.
The aim of the trial, led by Samer Najjar (MedStar Health Research Institute, Washington Hospital Center, USA), was to evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI who have undergone successful percutaneous coronary intervention (PCI) as primary or rescue reperfusion therapy.
The team randomly assigned participants to treatment with intravenous epoetin alfa or matching saline placebo, administered within 4 hours of reperfusion. The main outcome measure was infarct size, expressed as a percentage of left ventricular mass (LV). The team measured this using two sets of cardiac magnetic resonance (CMR) imaging: the first CMR was at 2-6 days after study medication administration, and the second CMR was done 12 weeks later. The trial consisted of a dose-escalation safety phase and a single dose (60,000 U of epoetin alfa) efficacy phase.
Reporting their findings in the JAMA, the researchers explain that in the efficacy cohort, infarct size did not differ between the epoetin alfa and placebo groups on either the first CMR (15.8% vs 15.0% LV mass) or second CMR scan (10.6% vs 10.4% LV mass).
Of the 125 patients who received epoetin alfa in the safety cohort, the composite outcome of death, MI, stroke, or stent thrombosis occurred in five (4.0%), whereas none of the 97 patients who received placebo had this outcome (p=0.04).
In a prespecified analysis of 21 patients aged 70 years or older, the average infarct size was larger in the epoetin alfa group in the first week (19.9% LV mass) than in the placebo group (11.7% LV mass, p=0.03).
"This raised concerns about an increase in infarct size among the small number of patients who were aged 70 years or older," comment the study authors.
In a related editorial, Deepak Bhatt (Harvard Medical School, Massachusetts, USA) said the study "seems to settle the debate about whether there is a therapeutic role for erythropoietin administration during primary PCI and is a useful negative finding."
He continued: "The totality of evidence strongly suggests that this class of medication has CV risk, most likely to manifest in higher-risk individuals. Until compelling data become available to support routine use of these agents in patients with anemia, it would be prudent to minimize their use, especially for patients at high risk for CV disease, or with an acute ischemic syndrome."
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By Piriya Mahendra