High-dose erythropoietin for tissue protection.
BACKGROUND
The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction. Experimental studies have been favourable, but the clinical efficacy has yet to be validated.


MATERIALS AND METHODS
We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of rHuEPO for this indication. A systematic literature search was performed using the PubMed/MEDLINE database for randomized, placebo-controlled clinical trials.


RESULTS
Twenty-six randomized controlled trials that enrolled 3176 patients were included. The majority of trials (20 trials including 2724 patients) reported no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality.


CONCLUSIONS
Evidence is sparse to support a tissue-protective benefit of rHuEPO in humans. Moreover, a number of studies indicate that short-term administration of high-dose rHuEPO is associated with an increased risk of mortality and serious adverse events. Further work is needed to elucidate the mechanisms of toxicity of rHuEPO in humans.
['Lund|Anton|A|', 'Lundby|Carsten|C|', 'Olsen|Niels V|NV|']
D002316:Cardiotonic Agents D019610:Cytoprotection D004921:Erythropoietin D006397:Hematinics D006801:Humans D007674:Kidney Diseases D018696:Neuroprotective Agents D016032:Randomized Controlled Trials as Topic D011994:Recombinant Proteins
erythropoietin Cardioprotection erythropoiesis stimulating agent nephroprotection neuroprotection