title: Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States.
abstract: OBJECTIVE
  Recombinant human erythropoietin (epoetin) is used routinely to increase blood hemoglobin levels in patients with ESRD and anemia. Although lower doses of epoetin are required to achieve equivalent hemoglobin responses when administered subcutaneously rather than intravenously, standard practice has been to administer epoetin to patients on hemodialysis intravenously. Randomized trials of alternative epoetin treatment regimens in patients with kidney failure have shown that risks of cardiovascular complications and death are related to the dose levels of epoetin used. Therefore, given the dose-sparing advantages of subcutaneous epoetin administration, the possibility that treatment of patients on hemodialysis with subcutaneous epoetin might be associated with more favorable outcomes compared with intravenous treatment was investigated.
  
  
  METHODS
  A retrospective cohort study of 62,710 adult patients on hemodialysis treated with either intravenous or subcutaneous epoetin-α and enrolled in the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project from 1997 to 2005 was carried out. Risks of death and/or hospitalization for cardiovascular complications (adverse composite event outcomes) during 2 years of follow-up were determined in relationship to epoetin dose and route of administration (intravenous versus subcutaneous) by multivariate Cox proportional hazard modeling adjusted for demographics and clinical parameters.
  
  
  RESULTS
  Epoetin doses used to achieve equivalent hemoglobin responses in study patients were, on average, 25% higher when epoetin was administered intravenously rather than subcutaneously (as expected). Moreover, adverse composite event outcomes were found to be significantly more likely to occur during follow-up for patients on hemodialysis managed with intravenous rather than subcutaneous epoetin (adjusted hazard ratio for adverse events within 1 year [intravenous versus subcutaneous] was 1.11 [95% confidence interval, 1.04 to 1.18]).
  
  
  CONCLUSIONS
  This study finds that treatment of patients on hemodialysis with subcutaneous epoetin is associated with more favorable clinical outcomes than those associated with intravenous epoetin treatment.
authors.affiliation: Molecular Medicine Branch, daniel.wright@nih.gov.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Wright
authors.affiliation: Biostatistics Program, and.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.affiliation: Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Narva
authors.affiliation: Molecular Medicine Branch.
authors.forename: Constance T
authors.initials: CT
authors.lastname: Noguchi
authors.affiliation: Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Eggers
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D000068817:Epoetin Alfa / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology; D006435:Renal Dialysis; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D014481:United States / Q000453:epidemiology
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D000068817:Epoetin Alfa
keywords: ESRD; anemia; epoetin; erythropoietin; hemodialysis