Intravenous Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction. REVEAL: A Randomized Controlled Trial
What is the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with ST-segment elevation myocardial infarction (STEMI)?
This was a prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60,000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October 2006 and February 2010, and included 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. Participants were randomly assigned 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 percentage of left ventricular (LV) mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2-6 days after study medication administration (first CMR), and again 12 ± 2 weeks later (second CMR).
In the efficacy cohort, the infarct size did not differ between groups on either the first CMR scan (n = 136; 15.8% LV mass; 95% confidence interval [CI], 13.3-18.2% LV mass for the epoetin alfa group vs. 15.0% LV mass; 95% CI, 12.6-17.3% LV mass for the placebo group; p = 0.67) or on the second CMR scan (n = 124; 10.6% LV mass; 95% CI, 8.4-12.8% LV mass vs. 10.4% LV mass; 95% CI, 8.5-12.3% LV mass, respectively; p = 0.89). In a prespecified analysis of patients ages 70 years or older (n = 21), the mean infarct size within the first week (first CMR) was larger in the epoetin alfa group (19.9% LV mass; 95% CI, 14.0-25.7% LV mass) than in the placebo group (11.7% LV mass; 95% CI, 7.2-16.1% LV mass) (p = 0.03). In the safety cohort, of the 125 patients who received epoetin alfa, the composite outcome of death, MI, stroke, or stent thrombosis occurred in five subjects (4.0%; 95% CI, 1.31%-9.09%), but in none of the 97 who received placebo (p = 0.04).
The authors concluded that in patients with STEMI who had successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size, and was associated with higher rates of adverse cardiovascular events.
In this study, a single bolus of intravenous epoetin alfa in patients with STEMI who underwent successful primary or rescue PCI failed to demonstrate a reduction in infarct size. Moreover, there was a significant increase in infarct size in prespecified analyses among older patients and also a significant increase in the composite of cardiovascular adverse events that included stent thrombosis. The results of this study and prior smaller studies suggest lack of any beneficial effect of erythropoietin on infarct size, and may in fact be harmful. Additional studies are needed to assess withholding of erythropoietin in patients who are receiving this medication for labeled indications, and who sustain an MI.
Keywords: Outcome Assessment (Health Care), Erythropoietin, Myocardial Infarction, Thrombosis, Ventricular Remodeling, Magnetic Resonance Spectroscopy, Percutaneous Coronary Intervention
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