title: Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00378352.
authors.affiliation: Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. Samer.S.Najjar@medstar.net
authors.forename: Samer S
authors.initials: SS
authors.lastname: Najjar
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Rao
authors.forename: Chiara
authors.initials: C
authors.lastname: Melloni
authors.forename: Subha V
authors.initials: SV
authors.lastname: Raman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: Laura
authors.initials: L
authors.lastname: Melton
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Barsness
authors.forename: Kristi
authors.initials: K
authors.lastname: Prather
authors.forename: John F
authors.initials: JF
authors.lastname: Heitner
authors.forename: Rakhi
authors.initials: R
authors.lastname: Kilaru
authors.forename: Luis
authors.initials: L
authors.lastname: Gruberg
authors.forename: Vic
authors.initials: V
authors.lastname: Hasselblad
authors.forename: Adam B
authors.initials: AB
authors.lastname: Greenbaum
authors.forename: Manesh
authors.initials: M
authors.lastname: Patel
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Kim
authors.forename: Mark
authors.initials: M
authors.lastname: Talan
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
mesh_terms: D000328:Adult; D000367:Age Factors; D015906:Angioplasty, Balloon, Coronary; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology; D010919:Placebos; D011994:Recombinant Proteins; D015607:Stents; D020521:Stroke; D013927:Thrombosis / Q000139:chemically induced; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D006397:Hematinics; D010919:Placebos; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa