Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia

Aims Anaemia is common in chronic heart failure (CHF) and associated with worse outcome. This randomized, double-blind, placebo -controlled study evaluated the effect of two darbepoetin alfa dosing regimens on haemoglobin (Hb) rate of rise and clinical effects in patients with CHF and anaemia. Methods and results Patients with CHF (>= 3 months), left ventricutar ejection fraction (LVEF) <= 40%, and Hb 9.0 to 12.5 g/dL received darbepoetin alfa subcutaneously every 2 weeks for 26 weeks at a starting weight adjusted dose of 0.75 mcg/kg (n = 56) or a fixed dose of 50 mcg In = 54), or placebo (n = 55), to gradually achieve and maintain a target Hb of 14.0 +/- 1.0 g/dL. Endpoints included rate of Hb rise per week during titration, safety, and changes in 6 min walk distance, New York Heart Association (NYHA) class, LVEF, and quality of life. Most subjects were NYHA class II-III. Mean (SD) age was 71 (11) years, LVEF was 28 (9), and Hb 11.5 (0.7) g/dL. Rate of Hb rise was equivalent between darbepoetin alfa weight-based (+1.87 +/- 1.36 g/dL) and fixed dosing (+1.64 +/- 0.98 g/dL) groups, vs. + 0.07 +/- 1.08 g/dL in the placebo group. Mean Hb concentrations by week 27 were 13.4 and 13.2 g/dL, in the weight-based and fixed dosing groups, respectively. There were non-significant improvements in the combined darbepoetin alfa group vs. placebo for 6 min walk distance (P = 0.074) and Patient's Global Assessment score (P = 0.057). There was a significant improvement in Kansas City Cardiomyopathy Questionnaire total symptom score (8.2 vs. 1.5 points; P = 0.027) but no change in NYHA class, LVEF, and Minnesota Living With Heart Failure Questionnaire score. Six treatment- unrelated deaths occurred in the 110 darbepoetin alfa treated patients, and none in the 55 placebo treated patients. Other adverse events were similar between groups. Conclusion In this study of patients with CHF and anaemia, treatment with darbepoetin alfa raised Hb using different dosing regimens. Darbepoetin alfa improved some quality of life indices, but its safety requires further exploration. Larger trials are needed to determine the effects on long-term morbidity and mortality.