title: Stroke in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia treated with Darbepoetin Alfa: the trial to reduce cardiovascular events with Aranesp therapy (TREAT) experience.
abstract: BACKGROUND
  More strokes were observed in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) among patients assigned to darbepoetin alfa. We sought to identify baseline characteristics and postrandomization factors that might explain this association.
  
  
  RESULTS
  A multivariate logistic regression model was used to identify baseline predictors of stroke in 4038 patients with diabetes mellitus, chronic kidney disease, and anemia randomized to receive darbepoetin alfa or placebo. To determine whether postrandomization blood pressure, hemoglobin level, platelet count, or treatment dose were responsible for the increased risk related to darbepoetin alfa, we performed a nested case-control analysis (1:10 matching) identifying nonstroke controls with propensity matching. The risk of stroke was doubled with darbepoetin alfa. Overall, 154 patients had a stroke, 101/2012 (5.0%) in the darbepoetin alfa arm and 53/2026 (2.6%) in the placebo arm (hazard ratio 1.9; 95% confidence interval, 1.4-2.7). Independent predictors of stroke included assignment to darbepoetin alfa (odds ratio 2.1; 95% confidence interval, 1.5-2.9), history of stroke (odds ratio 2.0; 95% confidence interval, 1.4-2.9), more proteinuria, and known cardiovascular disease. In patients assigned to darbepoetin alfa, postrandomization systolic and diastolic blood pressure, hemoglobin level, platelet count, and darbepoetin alfa dose did not differ between those with and without stroke. Additional sensitivity analyses using maximal values, latest values, or changes over varying periods of exposure yielded similar results.
  
  
  CONCLUSIONS
  The 2-fold increase in stroke with darbepoetin alfa in TREAT could not be attributed to any baseline characteristic or to postrandomization blood pressure, hemoglobin, platelet count, or dose of treatment. These readily identifiable factors could not be used to mitigate the risk of darbepoetin alfa-related stroke.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00093015.
authors: Brigham and Women's Hospital, Cardiovascular Division, 75 Francis St, Boston, MA 02115, USA.
authors: Hicham
authors: H
authors: Skali
authors: Hans-Henrik
authors: HH
authors: Parving
authors: Patrick S
authors: PS
authors: Parfrey
authors: Emmanuel A
authors: EA
authors: Burdmann
authors: Eldrin F
authors: EF
authors: Lewis
authors: Peter
authors: P
authors: Ivanovich
authors: Sai Ram
authors: SR
authors: Keithi-Reddy
authors: Janet B
authors: JB
authors: McGill
authors: John J V
authors: JJ
authors: McMurray
authors: Ajay K
authors: AK
authors: Singh
authors: Scott D
authors: SD
authors: Solomon
authors: Hajime
authors: H
authors: Uno
authors: Marc A
authors: MA
authors: Pfeffer
mesh_terms: D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000453:epidemiology*; D016022:Case-Control Studies; D000068256:Darbepoetin alfa; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005500:Follow-Up Studies; D006397:Hematinics / Q000008:administration & dosage; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology*; D012307:Risk Factors; D040242:Risk Reduction Behavior; D020521:Stroke / Q000453:epidemiology* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa