Dataset Information

EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy.

ABSTRACT: Erythropoietin (EPO) was hypothesized to mitigate reperfusion injury, in part via mobilization of endothelial progenitor cells (EPCs). The REVEAL trial found no reduction in infarct size with a single dose of EPO (60,000 U) in patients with ST-segment elevation myocardial infarction. In a substudy, we aimed to determine the feasibility of cryopreserving and centrally analyzing EPC levels to assess the relationship between EPC numbers, EPO administration, and infarct size. As a prespecified substudy, mononuclear cells were locally cryopreserved before as well as 24 and 48-72 h after primary percutaneous coronary intervention. EPC samples were collected in 163 of 222 enrolled patients. At least one sample was obtained from 125 patients, and all three time points were available in 83 patients. There were no significant differences in the absolute EPC numbers over time or between EPO- and placebo-treated patients; however, there was a trend toward a greater increase in EPC levels from 24 to 48-72 h postintervention in patients receiving ?30,000 U of EPO (P = 0.099 for CD133(+) cells, 0.049 for CD34(+) cells, 0.099 for ALDH(br) cells). EPC numbers at baseline were inversely related to infarct size (P = 0.03 for CD133(+) cells, 0.006 for CD34(+) cells). Local whole cell cryopreservation and central EPC analysis in the context of a multicenter randomized trial is feasible but challenging. High-dose (?30,000 U) EPO may mobilize EPCs at 48-72 h, and baseline EPC levels may be inversely associated with infarct size.

SUBMITTER: Povsic TJ

PROVIDER: S-EPMC4008147 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy.

Povsic Thomas J TJ Najjar Samer S SS Prather Kristi K Zhou Jiying J Adams Stacie D SD Zavodni Katherine L KL Kelly Francine F Melton Laura G LG Hasselblad Vic V Heitner John F JF Raman Subha V SV Barsness Gregory W GW Patel Manesh R MR Kim Raymond J RJ Lakatta Edward G EG Harrington Robert A RA Rao Sunil V SV

Journal of thrombosis and thrombolysis 20131101 4

Erythropoietin (EPO) was hypothesized to mitigate reperfusion injury, in part via mobilization of endothelial progenitor cells (EPCs). The REVEAL trial found no reduction in infarct size with a single dose of EPO (60,000 U) in patients with ST-segment elevation myocardial infarction. In a substudy, we aimed to determine the feasibility of cryopreserving and centrally analyzing EPC levels to assess the relationship between EPC numbers, EPO administration, and infarct size. As a prespecified subst ...[more]

PMID: 23700090

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Project description:CONTEXT:Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. OBJECTIVE:To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. DESIGN, SETTING, AND PATIENTS: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. INTERVENTION:Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. MAIN OUTCOME MEASURE:Infarct size, expressed as percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2 to 6 days after study medication administration (first CMR) and again 12 ± 2 weeks later (second CMR). RESULTS: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 = .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 = .89). In a prespecified analysis of patients aged 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 = .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 5 (4.0%; 95% CI, 1.31%-9.09%) but in none of the 97 who received placebo (P = .04). CONCLUSIONS: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. Subgroup analyses raised concerns about an increase in infarct size among older patients. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00378352.

Dataset Information

EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy.

Publications

EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy.

Similar Datasets

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