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

van der Meer, P. et al. (2018) 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. Circulation: Heart Failure, 11(2), e004431. (doi:10.1161/CIRCHEARTFAILURE.117.004431) (PMID:29367268)

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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. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215.

Item Type:Articles
Additional Information:The RED-HF trial was funded by Amgen, Inc.
Keywords:Anemia, darbepoetin alfa, erythropoietin, heart failure.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: van der Meer, P., Grote Beverborg, N., Pfeffer, M. A., Olson, K., Anand, I. S., Westenbrink, B. D., McMurray, J. J.V., Swedberg, K., Young, J. B., Solomon, S. D., and van Veldhuisen, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Circulation: Heart Failure
Publisher:American Heart Association
ISSN:1941-3289
ISSN (Online):1941-3297
Published Online:24 January 2018

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