Differences in blood volume components between hyporesponders and responders to erythropoietin alfa: the heart failure with preserved ejection fraction (HFPEF) anemia trial

Abstract

Background: Hyporesponders to erythropoietin-stimulating agents (ESAs) have been associated with an increased subsequent risk of death or cardiovascular events. We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy.

Methods: As part of a prospective, single blind, randomized, placebo-controlled study comparing erythropoietin alfa with placebo in older adults (n = 56) with heart failure and a preserved ejection fraction (HFPEF), we performed blood volume analysis with the use of an indicator dilution technique with (131)iodine-labeled albumin. We evaluated differences in plasma volumes and red cell volumes in hyporesponders (eg, <1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa) compared with subjects who were responders and controls.

Results: Nine of 28 subjects (32%) assigned to ESA were hyporesponders. Hyporesponders did not differ from responders nor control subjects by any baseline demographic, clinical, or laboratory parameter, including hemoglobin. Hyporesponders had a greater total blood volume expansion (1,264.7 ± 387 vs 229 ± 206 mL; P = .02) but less of a red cell deficit (-96.2 ± 126 vs -402.5 ± 80.6 mL; P = .04) and a greater plasma volume expansion (+1,360.8 ± 264.5 vs +601.1 ± 165.5 mL; P = .01). Among responders, the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume (r = 0.91; P < .0001) as well as a decline in plasma volume (r = -0.55; P = .06).

Conclusions: Among older adults with HFPEF and anemia, hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia, suggesting that blood volume analysis can identify a cohort likely to respond to therapy.

Keywords: Anemia; blood volume; erythropoietin alfa; heart failure.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Figure 1. Change in Hemoglobin during course of Trial in Controls. Responders and Hypo-Responders

Weekly Change in Hemoglobin from Baseline during course of trial in subjects assigned to placebo (controls) and epoetin alfa, the latter divided into responders and hypo-responders.

Figure 2. Change in Blood Volume After 6 Months

Change in blood volume and its components red cell volume and plasma volume after 6 Months of therapy with epoetin alfa in in subjects assigned to placebo (controls) and in responders and hypo-responders (see text for details).