title: Effect of erythropoiesis-stimulating agents in acute ST-segment elevation myocardial infarction: a systematic review.
abstract: OBJECTIVE
  Current evidence suggests that erythropoiesis-stimulating agents (ESAs), including erythropoietin and darbepoetin, may have a direct cardio-protective effect. However, randomized controlled trials (RCTs) assessing the efficacy and safety of ESAs in patients with acute ST-segment elevation myocardial infarction (STEMI) have yielded heterogeneous results. Here, we performed a meta-analysis of RCTs to assess whether the administration of ESAs can improve cardiac functional parameters, such as left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV), and attenuate infarct size in patients with acute STEMI.
  
  
  RESULTS
  The PubMed, EBSCO, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for relevant RCT studies on ESAs published before May 13, 2011. A total of nine RCTs involving 1,244 participants were identified. The original data of these studies were aggregated using fixed effect models. Compared with controls, the administration of ESAs showed a slight but significant improvement in LVEF (1.38%; 95% confidence interval 0.38-2.37%; p = 0.007). However, no significant improvement in LVEDV, LVESV, and infarct size was observed, and no increase in all-cause severe adverse effect was indicated.
  
  
  CONCLUSIONS
  Our meta-analysis indicates that the superiority of ESAs over conventional therapy in patients with acute STEMI is limited using current procedures. However, there is evidence to suggest that the timing and dosing of ESA administration may be optimized. Moreover, the long-term cardio-protective effect of ESAs in this patient population may be beneficial and worth exploring.
authors.affiliation: Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Huiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.forename: Yanting
authors.initials: Y
authors.lastname: Wen
mesh_terms: D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068256:Darbepoetin alfa; D004562:Electrocardiography / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; C554270:EPO protein, human; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa
references.citation: J Am Coll Cardiol. 2006 Jul 4;48(1):176-84
references.pmid: 16814664
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4802-6
references.pmid: 12663857
references.citation: BMJ. 2001 Jul 7;323(7303):42-6
references.pmid: 11440947
references.citation: Blood. 2003 Aug 15;102(4):1340-6
references.pmid: 12702503
references.citation: Nature. 1998 Oct 1;395(6701):511-6
references.pmid: 9774108
references.citation: Biochem Biophys Res Commun. 2003 Sep 5;308(4):990-4
references.pmid: 12927817
references.citation: Int J Cardiol. 2009 Jan 9;131(2):285-7
references.pmid: 17931721
references.citation: Circ J. 2010 Nov;74(11):2365-71
references.pmid: 20834185
references.citation: Circ Res. 2004 Nov 12;95(10):957-70
references.pmid: 15539639
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11612-7
references.pmid: 14500913
references.citation: JAMA. 2011 May 11;305(18):1863-72
references.pmid: 21558517
references.citation: Expert Rev Mol Med. 2008 Dec 01;10:e36
references.pmid: 19040789
references.citation: Eur J Heart Fail. 2004 Dec;6(7):853-9
references.pmid: 15556046
references.citation: Stroke. 2009 Dec;40(12):e647-56
references.pmid: 19834012
references.citation: Circulation. 2008 Jan 29;117(4):526-35
references.pmid: 18195176
references.citation: Trends Pharmacol Sci. 2008 May;29(5):258-67
references.pmid: 18359096
references.citation: J Cardiovasc Pharmacol. 2004 Oct;44(4):473-9
references.pmid: 15454856
references.citation: Cardiovasc Drugs Ther. 2006 Apr;20(2):135-41
references.pmid: 16761193
references.citation: Physiol Rev. 1992 Apr;72(2):449-89
references.pmid: 1557429
references.citation: Biochemistry. 1996 Feb 6;35(5):1681-91
references.pmid: 8634300
references.citation: Circulation. 2003 Jan 21;107(2):294-9
references.pmid: 12538431
references.citation: Lab Invest. 1996 Jan;74(1):86-107
references.pmid: 8569201
references.citation: Cardiovasc Res. 2008 Sep 1;79(4):549-50
references.pmid: 18583337
references.citation: Circulation. 2003 Jul 29;108(4):432-7
references.pmid: 12860910
references.citation: Circ J. 2010 Jul;74(7):1415-23
references.pmid: 20501957
references.citation: Heart. 2009 Aug;95(16):1309-14
references.pmid: 19168472
references.citation: Cardiovasc Drugs Ther. 2005 Aug;19(4):243-50
references.pmid: 16187008
references.citation: Int J Cardiol. 2011 Jun 2;149(2):216-220
references.pmid: 20199815
references.citation: J Biol Chem. 2006 Mar 17;281(11):7002-11
references.pmid: 16414957
references.citation: Circ Cardiovasc Interv. 2010 Oct;3(5):408-13
references.pmid: 20736448
references.citation: Am J Cardiol. 2009 Oct 15;104(8):1035-40
references.pmid: 19801020
references.citation: Eur Heart J. 2010 Nov;31(21):2593-600
references.pmid: 20802250
references.citation: Int J Cardiol. 2011 Feb 17;147(1):124-31
references.pmid: 19906454
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120