title: Longer-term outcomes of darbepoetin alfa versus epoetin alfa in patients with ESRD initiating hemodialysis: a quasi-experimental cohort study.
abstract: BACKGROUND
  Adequately powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking.
  
  
  METHODS
  Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis therapy in facilities (almost) exclusively using DPO versus EPO.
  
  
  METHODS
  Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure.
  
  
  METHODS
  DPO versus EPO.
  
  
  RESULTS
  All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke.
  
  
  METHODS
  Unadjusted and adjusted HRs from Cox proportional hazards regression models.
  
  
  RESULTS
  Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99-1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94-1.16). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. We found no differences in adjusted stroke or MI rates or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96-1.25).
  
  
  CONCLUSIONS
  Nonrandom treatment assignment, potential residual confounding.
  
  
  CONCLUSIONS
  In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.
authors.affiliation: Section of Nephrology, Baylor College of Medicine, Houston, TX; Division of Nephrology, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA. Electronic address: winkelma@bcm.edu.
authors.forename: Wolfgang C
authors.initials: WC
authors.lastname: Winkelmayer
authors.affiliation: Division of Nephrology, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Tara I
authors.initials: TI
authors.lastname: Chang
authors.affiliation: Division of General Medical Disciplines, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Aya A
authors.initials: AA
authors.lastname: Mitani
authors.affiliation: Division of Nephrology, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Emilee R
authors.initials: ER
authors.lastname: Wilhelm-Leen
authors.affiliation: Division of General Medical Disciplines, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ding
authors.affiliation: Division of Nephrology, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
authors.forename: M Alan
authors.initials: MA
authors.lastname: Brookhart
authors.affiliation: Division of General Medical Disciplines, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA; Duke University School of Medicine, Durham, NC.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Goldstein
mesh_terms: D000368:Aged; D000554:Ambulatory Care Facilities; D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D015897:Comorbidity; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006436:Hemodialysis Units, Hospital; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000627:therapeutic use; D012042:Registries; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000401:mortality*; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa
keywords: Mortality; cardiovascular; darbepoetin alfa (DPO); epoetin alfa (EPO); erythropoiesis-stimulating agent (ESA); hemodialysis; myocardial infarction; recombinant erythropoietin; renal replacement therapy (RRT); safety; stroke