title: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease.
abstract: BACKGROUND
  Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested.
  
  
  METHODS
  In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease.
  
  
  RESULTS
  Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P=0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P=0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group.
  
  
  CONCLUSIONS
  The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.)
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mpfeffer@rics.bwh.harvard.edu
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Burdmann
authors.forename: Chao-Yin
authors.initials: CY
authors.lastname: Chen
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
authors.forename: Jan M
authors.initials: JM
authors.lastname: Feyzi
authors.forename: Peter
authors.initials: P
authors.lastname: Ivanovich
authors.forename: Reshma
authors.initials: R
authors.lastname: Kewalramani
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Patrick
authors.initials: P
authors.lastname: Parfrey
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Singh
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Robert
authors.initials: R
authors.lastname: Toto
mesh_terms: D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D000068256:Darbepoetin alfa; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa