The authors report their results of a large, prospective, randomized trial of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa vs. placebo in the management of anemia in 2,278 patients with NYHA Class II-IV congestive heart failure (LVEF ≤ 40% and hemoglobin concentration 9-12 g/dL). Patients determined to have iron-deficiency anemia (TSAT less than 15%) were not eligible. Patients with ESRD or uncontrolled hypertension were also not eligible. During the course of treatment if TSAT decreased below 20%, patients received oral or intravenous iron therapy.
The median entry hemoglobin level of 11.2 g/dL increased to 13.0 g/dL in the ESA cohort vs. 11.5 g/dL in the placebo cohort. The primary composite outcome (death from any cause or first hospitalization for worsening heart failure) occurred in 50.7% of the ESA cohort vs. 49.5% in the placebo group (HR 1.01, CI 0.90-1.13). Similarly, deaths from any cause or cardiovascular causes were also not different. Embolic and thrombotic adverse events were reported in 13.5% of the ESA cohort compared to 10.0% in the placebo (P = 0.01).
This study found that treatment with darbepoetin alfa led to successful management of anemia, with an early and sustained increase in hemoglobin level; but, despite this improvement and successful management of anemia, the use of darbepoetin alfa did not reduce the risk of the primary outcome of death or hospitalization for worsening heart failure. Moreover, there was a significant increase in the risk of thromboembolic events among patients receiving darbepoetin alfa. It is noteworthy that the authors did not report in their analysis whether there was a reduction in blood transfusions received in the ESA cohort compared to the placebo cohort.
– Lawrence Tim Goodnough