title: Increased risk of stroke with darbepoetin alfa in anaemic heart failure patients with diabetes and chronic kidney disease.
abstract: OBJECTIVE
  The use of an erythropoesis-stimulating agent, darbepoetin alfa (DA), to treat anaemia in patients with diabetes mellitus and chronic kidney disease was associated with a heightened risk of stroke and neutral efficacy in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), despite epidemiological data suggesting the contrary. However, this association has not been evaluated in another randomized, placebo-controlled trial.
  
  
  RESULTS
  Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) was a randomized placebo-controlled trial of DA in 2278 patients with systolic heart failure and anaemia, enrolled from 2006 to 2012 and followed for a median of 28 months. Within RED-HF, 816 patients had diabetes mellitus and chronic kidney disease [estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m(2) ] and met inclusion criteria for TREAT. TREAT-like RED-HF patient data were analysed alone and combined at the patient level with the 4038 TREAT patients. In RED-HF, the annualized event rate of stroke was 2.3 in patients on DA and 1.1 in patients randomized to placebo (P = 0.051). Analysis of the combined group (n = 4854) confirmed a nearly two-fold increase in stroke risk [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.43-2.63] and an overall neutral effect on mortality (HR 1.00, 95% CI 0.89-1.12) of raising haemoglobin with DA.
  
  
  CONCLUSIONS
  The placebo-controlled cohort of heart failure patients with anaemia, diabetes mellitus, and chronic kidney disease from RED-HF provides confirmation of the increased stroke risk associated with DA use identified in TREAT.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.|Division of Cardiology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Bello
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Desai
authors.affiliation: VA Medical Center and University of Minnesota, Minneapolis, MN, USA.
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.affiliation: Monash University and the Alfred Hospital, Victoria, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Amgen, Thousand Oaks, CA, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Olson
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000150:complications / Q000188:drug therapy; D000068256:Darbepoetin alfa / Q000008:administration & dosage / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000150:complications*; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000175:diagnosis; D018570:Risk Assessment; D012307:Risk Factors; D013223:Statistics as Topic; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control
chemical_list: D006397:Hematinics; D000068256:Darbepoetin alfa
keywords: Anaemia; Diabetes mellitus; Erythropoesis-stimulating agent; Heart failure; Renal dysfunction; Stroke