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.

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.

• Authors: 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
• Journal: Circulation. Heart failure (Circ Heart Fail) Vol. 11 Issue 2 Pg. e004431 (02 2018) ISSN: 1941-3297 [Electronic] United States
• PMID: 29367268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 American Heart Association, Inc.

Chemical References

• Hematinics
• Darbepoetin alfa

Topics

• Aged
• Anemia (complications, diagnosis, drug therapy)
• Darbepoetin alfa (adverse effects, pharmacology)
• Female
• Heart Failure, Systolic (complications, diagnosis, drug therapy)
• Hematinics (pharmacology)
• Humans
• Male
• Middle Aged
• Prognosis
• Renal Insufficiency, Chronic (drug therapy)
• Treatment Outcome