INTRODUCTION 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). CONCLUSION EPO therapy significantly improved long-term neurological outcomes in patients after IS. TRIAL REGISTRATION ISRCTN71371114 . Registered 10 October 2008.