title: Erythropoietin improves long-term neurological outcome in acute ischemic stroke patients: a randomized, prospective, placebo-controlled clinical trial.
abstract: BACKGROUND
  Mortality and disability following ischemic stroke (IS) remains unacceptably high with respect to the conventional therapies. This study tested the effect of erythropoietin (EPO) on long-term neurological outcome in patients after acute IS. This study aimed to evaluate the safety and efficacy of two consecutive doses of EPO (5,000 IU/dose, subcutaneously administered at 48 hours and 72 hours after acute IS) on improving the 90-day combined endpoint of recurrent stroke or death that has been previously reported. A secondary objective was to evaluate the long-term (that is, five years) outcome of patients who received EPO.
  
  
  METHODS
  This was a prospective, randomized, placebo-controlled trial that was conducted between October 2008 and March 2010 in a tertiary referral center. IS stroke patients who were eligible for EPO therapy were enrolled into the study.
  
  
  RESULTS
  The results showed that long-term recurrent stroke and mortality did not differ between group 1 (placebo-control; n = 71) and group 2 (EPO-treated; n = 71). Long-term Barthel index of <35 (defining a severe neurological deficit) was lower in group 2 than group 1 (P = 0.007). Multiple-stepwise logistic-regression analysis showed that EPO therapy was significantly and independently predictive of freedom from a Barthel index of <35 (P = 0.029). Long-term major adverse neurological event (MANE; defined as: death, recurrent stroke, or long-term Barthel index < 35) was lower in group 2 than group 1 (P = 0.04). Log-Rank test showed that MANE-free rate was higher in group 2 than group 1 (P = 0.031). Multiple-stepwise Cox-regression analysis showed that EPO therapy and higher Barthel Index at day 90 were independently predictive of freedom from long-term MANE (all P <0.04).
  
  
  CONCLUSIONS
  EPO therapy significantly improved long-term neurological outcomes in patients after IS.
  
  
  BACKGROUND
  ISRCTN71371114 . Registered 10 October 2008.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. u401119@yahoo.com.tw.
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. chlu99@adm.cgmh.org.tw.
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Department of Plastic Surgery, University Hospital of South Manchester, Southmoor Road, Manchester, M23 9LT, UK. c.g.wallace@gmail.com.
authors.forename: Christopher Glenn
authors.initials: CG
authors.lastname: Wallace
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. cwenneng@ms19.hinet.net.
authors.forename: Wen-Neng
authors.initials: WN
authors.lastname: Chang
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. fangoe@adm.cgmh.org.tw.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Chen
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. kcn68@ms22.hinet.net.
authors.forename: Chi-Ren
authors.initials: CR
authors.lastname: Huang
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. tsainw@yahoo.com.tw.
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Tsai
authors.affiliation: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. myl@ksts.seed.net.tw.
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Lan
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. e12281@cgmh.org.tw.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.affiliation: Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. leou4503@adm.cgmh.org.tw.
authors.forename: Chu-Feng
authors.initials: CF
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. han.gung@msa.hinet.net.|Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. han.gung@msa.hinet.net.|Institute of Shock Wave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. han.gung@msa.hinet.net.|Chang Gung University College of Medicine, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Hsien, 83301, Taiwan. han.gung@msa.hinet.net.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy; D066026:Endothelial Progenitor Cells / Q000502:physiology; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D011446:Prospective Studies; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D004921:Erythropoietin