title: Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials.
abstract: BACKGROUND
  Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure.
  
  
  METHODS
  An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613).
  
  
  RESULTS
  Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2-188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0-121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (-0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (-226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure-related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37-0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34-0.99, P = .047) was observed, although the number of events was limited.
  
  
  CONCLUSIONS
  Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.
authors.affiliation: Clinical Trials & Evaluation Unit, Royal Brompton Hospital & National Heart and Lung Institute, Imperial College, London, UK. Dipak.Kotecha@monash.edu
authors.forename: Dipak
authors.initials: D
authors.lastname: Kotecha
authors.forename: Katherine
authors.initials: K
authors.lastname: Ngo
authors.forename: Julia A E
authors.initials: JA
authors.lastname: Walters
authors.forename: Luis
authors.initials: L
authors.lastname: Manzano
authors.forename: Alberto
authors.initials: A
authors.lastname: Palazzuoli
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Flather
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D004921:Erythropoietin / Q000627:therapeutic use*; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D004921:Erythropoietin