title: Use of erythropoiesis-stimulating agents in the treatment of anemia in patients with systolic heart failure.
abstract: OBJECTIVE
  To determine the efficacy and safety of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with systolic heart failure.
  
  
  METHODS
  A search of MEDLINE (1946-January 2014) and EMBASE (1947-January 2014) was conducted using the search terms erythropoietin and systolic heart failure. In addition, bibliographies of relevant articles were reviewed for additional citations.
  
  
  METHODS
  All English language randomized controlled trials evaluating clinical outcomes or adverse events when using ESAs in the setting of systolic heart failure were included.
  
  
  RESULTS
  A total of 9 studies were reviewed. All studies examining hematological parameters found a statistically significant increase in hemoglobin levels with active treatment versus placebo. Of the 7 trials evaluating exercise tolerance or capacity, only 4 demonstrated statistically significant improvement in these measures in patients receiving ESAs, whereas the remainder showed no clinical benefit. Four studies examined quality-of-life measures. Although numerical improvements were observed in most trials, statistical significance was reached in only 2 trials. A nonsignificant trend for decreased mortality in patients treated with darbepoetin with a similar adverse event profile compared to placebo was shown in one study; however, the largest trial to date showed no benefit in all-cause mortality or heart failure-related hospitalizations with the use of ESAs. Additionally, a statistically significant increase in the number of cerebrovascular events and thrombotic events was found.
  
  
  CONCLUSIONS
  There is inconclusive evidence to suggest that the use of ESAs in treating anemia in patients with heart failure is beneficial. Although ESAs demonstrated a clear ability for increasing hemoglobin levels, the data regarding clinical outcomes such as exercise parameters, quality of life, and hospitalizations are conflicting. In addition, a mortality benefit has not been shown; therefore, the potential for improved symptomatology must be weighed against the potential for adverse events.
authors.affiliation: Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.
authors.forename: Desirae E
authors.initials: DE
authors.lastname: Lindquist
authors.affiliation: Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC, USA jcruzpharmd@gmail.com.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cruz
authors.affiliation: Pharmacy Service, Durham VA Medical Center, Durham, NC, USA.
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Brown
mesh_terms: D000740:Anemia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D054143:Heart Failure, Systolic / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods
chemical_list: D006397:Hematinics
keywords: anemia; darbepoetin; disease management; erythropoietin; heart failure; quality of life