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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, Peter Beverborg, Niels Grote Pfeffer, Marc A. Olson, Kurt Anand, Inder S. Westenbrink, B. Daan McMurray, John Sweberg, Karl Young, James B. Solomon, Scott
van der Meer, Peter
Beverborg, Niels Grote
Pfeffer, Marc A.
Olson, Kurt
Anand, Inder S.
Westenbrink, B. Daan
McMurray, John
Sweberg, Karl
Young, James B.
Solomon, Scott
Citations
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Author
van der Meer, Peter
Beverborg, Niels Grote
Pfeffer, Marc A.
Olson, Kurt
Anand, Inder S.
Westenbrink, B. Daan
McMurray, John
Sweberg, Karl
Young, James B.
Solomon, Scott
van Veldhuisen, Dirk J.
Beverborg, Niels Grote
Pfeffer, Marc A.
Olson, Kurt
Anand, Inder S.
Westenbrink, B. Daan
McMurray, John
Sweberg, Karl
Young, James B.
Solomon, Scott
van Veldhuisen, Dirk J.
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.
Keywords
darbepoetin alfa, heart failure, erythropoietin, anemia
Date
2018
Type
Journal article
Journal
Circulation: Heart Failure
Book
Volume
11
Issue
2
Page Range
1-5
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled
Notes
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