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RED-HF: Darbepoetin alfa failed to improve systolic HF, anemia
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SAN FRANCISCO — Treatment with darbepoetin alfa did not improve clinical outcomes in a cohort of patients with systolic heart failure and mild to moderate anemia, according to study results presented at the American College of Cardiology Scientific Sessions and later published in The New England Journal of Medicine.
Anemia is common among patients with heart failure (HF). Those who develop anemia experience more severe symptoms, lower functional capacity, poorer quality of life and worse outcomes.
Prior study findings have suggested that treatment with an erythropoiesis-stimulating agent to increase hemoglobin levels may reduce hospitalization and improve functional capacity among patients with HF and anemia, but the evidence is not definitive, according to background information provided by researchers.
Karl Swedberg, MD, PHD, of the department of molecular and clinical medicine of Sahlgrenska Academy at University of Gothenburg, Sweden, and colleagues conducted a randomized, double blind trial to determine whether treatment with darbepoetin alfa (Aranesp, Amgen) — a synthetic form of erythropoietin — would improve outcomes among this patient population.
The investigation included 2,278 patients with systolic HF and mild to moderate anemia, defined as hemoglobin levels of 9 g/dL to 12 g/dL.
Researchers randomly assigned patients to receive darbepoetin alfa or placebo. The study drug was designed to increase hemoglobin levels to a target of 13 g/dL.
A composite of death from any cause or hospitalization for worsening HF served as the primary endpoint. Secondary outcomes included death from any cause, the composite of death from cardiovascular causes or first hospitalization for worsening HF, and change in overall summary score and symptom frequency score from baseline to 6 months.
After a median follow-up of 28 months, patients assigned to darbepoetin alfa attained a median hemoglobin level of 13 g/dL compared with 11.5 g/DL among patients assigned to placebo (P<.001).
“The between-group difference in the hemoglobin level was significant by 1 month after randomization and remained so throughout the study,” Swedberg and colleagues wrote.
Despite the sustained increase in hemoglobin levels, darbepoetin alfa did not reduce the risk for primary outcome measures.
Death or hospitalization for worsening HF occurred in 576 (50.7%) patients assigned to the study drug and 565 (49.5%) of patients assigned to placebo (HR=1.01; 95% CI, 0.90-1.13). The result remained consistent across all patient subgroups.
Researchers observed no significant difference in secondary outcomes between the two study arms.
Researchers said 221 patients (19.5%) assigned to darbepoetin alfa and 229 patients (20.1%) assigned to placebo discontinued treatment due to adverse events (P=.73).
Consistent with prior research, patients assigned to darbepoetin alfa experienced higher rates of stroke (3.7% vs. 2.7%; P=.23). They also had higher rates of thromboembolic adverse events (13.5% vs. 10%; P=.01). Overall annualized mortality rates were 14.4% among patients assigned to the study drug and 13.8% among those who received placebo (HR=1.04; 95% CI, .92-1.19).
“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,” Swedberg and colleagues concluded.
For more information:
Swedberg K. Abstract #751-3. Presented at: American College of Cardiology Scientific Sessions; March 9-11, 2013; San Francisco.
Swedberg K. N Engl J Med. 2013;doi:10.1056/NEJMoa1214865.
Disclosure: The study was sponsored by Amgen.
Perspective
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Harry S. Jacob, MD, FRCPath(Hon)
I am troubled by the conclusions of this paper. The studied ‘anemia’ cohort measured only about 11 g/dL — hardly a level that most of us would treat with an erythropoietic drug. In fact, this minimally anemic group did have a significant improvement in quality of life, albeit not in survival. One wonders whether patients with hemoglobin levels below 10 might, in fact, survive longer and with less morbidity if treated with darbepoetin or similar congeners.
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