title: Mortality risk of darbepoetin alfa versus epoetin alfa in patients with CKD: systematic review and meta-analysis.
abstract: BACKGROUND
  Epoetin alfa (EPO) and darbepoetin alfa (DPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No study has specifically compared the risks of hard study outcomes between EPO and DPO, including mortality.
  
  
  METHODS
  Systematic review of the literature and meta-analysis.
  
  
  METHODS
  Patients enrolled in randomized trials comparing EPO versus DPO for the treatment of anemia in adults with chronic kidney disease, including those requiring dialysis.
  
  
  METHODS
  We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) and industry resources, using predefined search terms and data abstraction tools. We then summarized key characteristics and findings of these trials and performed a random-effects meta-analysis of trials with at least 3 months' duration to identify the summary OR of mortality between patients randomly assigned to DPO versus EPO.
  
  
  METHODS
  DPO versus EPO.
  
  
  RESULTS
  All-cause mortality.
  
  
  RESULTS
  We identified 9 trials that met the stated inclusion criteria. Overall, 2,024 patients were included in the meta-analysis, of whom 126 died during follow-up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomly assigned to DPO versus EPO (OR, 1.33; 95% CI, 0.88-2.01). No treatment heterogeneity across studies was detected (Q statistic=4.60; P=0.8).
  
  
  CONCLUSIONS
  Generalizability to nontrial populations is uncertain.
  
  
  CONCLUSIONS
  Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately powered randomized trials, observational postmarketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents.
authors: Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA.
authors: Emilee R
authors: ER
authors: Wilhelm-Leen
authors: Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA; Section of Nephrology, Baylor College of Medicine, Houston, TX. Electronic address: winkelma@bcm.edu.
authors: Wolfgang C
authors: WC
authors: Winkelmayer
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D002423:Cause of Death; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality / Q000628:therapy; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000627:therapeutic use; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000401:mortality*
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa
keywords: Erythropoiesis-stimulating agents; anemia; carbohydrate side chain; chronic kidney disease (CKD); darbepoetin alfa (DPO); drug safety; end-stage renal disease (ESRD); epoetin alfa (EPO); hemoglobin variability; meta-analysis; mortality; recombinant human erythropoietin (rHuEPO)
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