Treating anemia in older adults with heart failure with a preserved ejection fraction with epoetin alfa: single-blind randomized clinical trial of safety and efficacy

Abstract

Background: Anemia is a common comorbidity in older adults with heart failure and a preserved ejection fraction and is associated with worse outcomes. We hypothesized that treating anemia with subcutaneous epoetin alfa would be associated with reverse ventricular remodeling and improved exercise capacity and health status compared with placebo.

Methods and results: Prospective, randomized, single-blind, 24-week study with blinded end point assessment among anemic (average hemoglobin of 10.4±1 g/dL) older adult patients (n=56; 77±11 years; 68% women) with heart failure and a preserved ejection fraction (ejection fraction=63±15%; B-type natriuretic peptide=431±366 pg/mL) was conducted. Treatment with epoetin alfa resulted in significant increases in hemoglobin (P<0.0001). Changes in end-diastolic volume (-6±14 versus -4±16 mL; P=0.67) at 6 months did not differ between epoetin alfa and placebo, but declines in stroke volume (-5±8 versus 2±10 mL; P=0.09) without significant changes in left ventricular mass were observed. Changes in 6-minute walk distance (16±11 versus 5±12 m; P=0.52) did not differ. Although quality of life improved by the Kansas City Cardiomyopathy Questionnaire and the Minnesota Living with Heart Failure Questionnaire in both cohorts, there were no significant differences between groups.

Conclusions: Administration of epoetin alfa to older adult patients with heart failure and a preserved ejection fraction compared with placebo did not change left ventricular end-diastolic volume and left ventricular mass nor did it improve submaximal exercise capacity or quality of life.

Clinical trial registration: URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00286182.

Figures

Figure 1

The CCORT chart delineating the flow of patients through the trial.

Figure 2

Weekly changes in hemoglobin from baseline during study period in subjects randomized to ESA (red circles) or placebo (blue triangles). Data represents mean ± standard error.

Figure 3

Left ventricular end diastolic volume derived from three dimensional echocardiography, the primary endpoint of the study in subjects randomized to ESA (red circles) or placebo (blue triangles). Data represents mean ± standard error.

Figure 4

Distribution of NYHA class after 6 months in ESA (red bars) and placebo (blue bars) (upper left panel); six minute hall walk distance in ESA (red circles and placebo (blue triangles) (upper right panel); peak VO2 in ESA (red circles) and placebo (blue triangles) (lower left panel) and quality of life measures for KCCQ (solid lines) and MLWFQ (dashed lines) (lower right panel) at baseline and after 3 and 6 months of therapy.