Hyporesponsiveness to darbepoetin alfa in patients with heart failure and anemia in the RED-HF Study (Reduction of events by darbepoetin alfa in heart failure): Clinical and prognostic associations

Peter Van Der Meer, Niels Grote Beverborg, Marc A. Pfeffer, Kurt Olson, Inder S. Anand, B. Daan Westenbrink, John J.V. McMurray, Karl Swedberg, James B. Young, Scott D. Solomon, Dirk J. Van Veldhuisen

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

BACKGROUND: A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. METHODS AND RESULTS: We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0–12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02–1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04–1.63) than responders. CONCLUSIONS: A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers.

Original languageEnglish (US)
Article numbere004431
JournalCirculation: Heart Failure
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2018

Keywords

  • Anemia
  • Darbepoetin alfa
  • Erythropoietin
  • Heart failure

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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