Washington, DC - Anemia may be common and a bad prognostic sign in patients with heart failure, but whether correcting it with erythropoiesis-stimulating agents improves their outcomes has been an open question. That hasn't quite changed with the publication of a tiny placebo-controlled trial in which the intervention improved patient quality-of-life scores but made no significant impact on NYHA functional class or objective measures of exercise capacity [1]. But its findings, including favorable trends in some potentially important functional end points, helps keep the door open for more substantive benefits in larger trials, according to the authors.

Somewhat strengthening the results was a significant correlation between expected hemoglobin increases from the active therapy, darbepoetin alfa (Aranesp, Amgen), and the less-than-significant (p=0.075) gains in exercise time, notes the report from Dr Piotr Ponikowski (Military Hospital, Wroclaw, Poland) and associates. The drug was well tolerated, the group writes.

Their report is published in the February 20, 2007 issue of the Journal of the American College of Cardiology.

The "elegant" study's results "suggest that correction of low hemoglobin levels in patients with HF is safe and improves their quality of life," writes Prof Michel Komajda (Université Pierre et Marie Curie, Paris, France) in an accompanying editorial [2]. "They support the idea of conducting larger placebo-controlled randomized trials with [erythropoietic agents] in anemic patients with HF to assess the safety and the potential benefit of this intervention on hospitalizations, functional capacity, quality of life, and exercise tolerance." But for now, he observed, there's no basis for recommending the drugs specifically for the management of HF.

Compared with the study's 22 patients who received placebo, the 19 treated with darbepoetin for six months showed no significant differences in the primary end point of change in weight-adjusted peak oxygen uptake (VO₂) nor in absolute change in VO₂, exercise duration, body weight, brain-type natriuretic peptide levels, or hospitalization rate.

Eligibility for the trial included HF with an LVEF <40%, hemoglobin levels from 9.0 g/dL to 12.0 g/dL, peak VO₂ reproducibly at 16 mL/kg per minute or less, and maintenance on optimal medical therapy. Darbepoetin was given subcutaneously in double-blind fashion every two weeks to a target hemoglobin range of 13 g/dL to 15 g/dL.

Actively treated patients were significantly more likely to report quality-of-life improvement on one of three self-assessments. By week 27, 79% of them, compared with 41% of control patients (p=0.01), showed improvement according to the Patient's Global Assessment of Change, but there were no such gains in Kansas City Cardiomyopathy and Minnesota Living with Heart Failure Questionnaire scores.

Komajda observes that more than half the darbepoetin recipients were only in NYHA functional class 2. "We do not know at present whether only severely symptomatic patients or patients with severe anemia might benefit [from erythropoietic agents] or whether a broader spectrum of patients could improve under this therapy."