March 10th, 2013
Another Negative Trial of Darbepoetin Alfa
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Once again a trial testing the erythropoiesis-stimulating agent darbepoetin alfa (Aranesp, Amgen) has produced a negative result. Results of the RED-HF (Reduction of Events by Darbepoetin Alfa in Heart Failure) trial were presented at the ACC in San Francisco and published simultaneously in the New England Journal of Medicine.
A total of 2278 patients with systolic heart failure and mild-to-moderate anemia were randomized to darbepoetin alfa (Aranesp, Amgen) or placebo. As expected, treatment with darbepoetin alfa significantly improved hemoglobin levels. However, no significant improvements in outcomes were associated with darbepoetin alfa.
The primary endpoint — all cause mortality or hospitalization for worsening heart failure — occurred in 50.7% of the darbepoetin alfa group and 49.5% of the placebo group (HR, 1.01; 95% CI, 0.90-1.13; P=0.87). Strokes occurred in 3.7% of the darbepoetin alfa group and 2.7% of the placebo group (HR, 1.33; 95% CI, 0.83-2.12; P=0.23). The RED-HF investigators noted that this observation was consistent with an elevated risk for stroke associated with darbepoetin alfa found in the TREAT trial of patients with diabetes, chronic kidney disease, and anemia.
A similar number of adverse events took place in each group, but a significant excess of embolic and thrombotic events occurred in the darbepoetin alfa group (13.5% vs. 10.0%; P=0.01).
The authors conclude that “our findings suggest that the hemoglobin level, like other surrogates, is simply a marker of poor prognosis in heart failure rather than a therapeutic target.” The trial, they write, does “not support the use of darbepoetin alfa in patients with systolic heart failure and mild-to-moderate anemia.”