New research from Brigham and Women's Hospital (BWH) shows that the current clinical strategy of using erythropoiesis stimulating agents (ESAs), a common anemia treatment, to reach certain hemoglobin targets in patients with chronic kidney disease not on dialysis and type 2 diabetes may be flawed. Researchers assessed the relationship between an individual's initial hemoglobin response to darbepoetin, a commonly used ESA, and clinical outcomes, and found that patients who had the least increase in hemoglobin to the first two doses of darbepoetin were at greatest risk of death or cardiovascular events, yet received the highest doses of the drug. This research appears in the September 16 issue of the New England Journal of Medicine.
In dialysis patients with very low hemoglobins, ESAs are credited with improved quality of life and reduced need for blood transfusions. Their use in patients with chronic kidney disease not on dialysis is more controversial, with recent studies suggesting worse outcomes at higher compared with lower hemoglobin targets when this population is treated with ESAs. In the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), patients with type 2 diabetes, anemia and chronic kidney disease not on dialysis were randomly assigned to receive placebo or darbepoetin, and the dose of darbepoetin was adjusted to attempt to achieve a target hemoglobin level of 13 g/dl.
"Currently, patients with chronic kidney disease and anemia are commonly treated with ESAs to raise hemoglobin to a particular target range. While the recommended target range has been declining in response to recent data suggesting harm at higher hemoglobin targets, our data suggest that it is the individual's responsiveness to the drug, and not the target hemoglobin level, that is associated with increased risk. In the trial, as in clinical practice, the dose is increased to achieve a target hemoglobin range, resulting in the least responsive patients receiving the most drug. We found that these patients had the worse outcomes" said Scott D. Solomon, MD, lead author of the paper and director of Noninvasive Cardiology at Brigham and Women's Hospital, and Associate Professor of Medicine at Harvard Medical School.
"Our findings indicate that the practice of treating to the currently recommended hemoglobin targets may not mitigate the potential risks associated with ESA use in patients with chronic kidney disease not on dialysis, " said Marc A. Pfeffer, MD, PhD, Principal Investigator of TREAT, Senior physician at Brigham and Women's Hospital and the Dzau Professor of Medicine at Harvard Medical School.
Dr. Solomon noted that their work could not determine whether the poorer outcomes in these less responsive patients was due to the possibility that they were sicker to begin with, or whether they received higher ESA doses, or both.
TREAT was supported by and conducted in collaboration with AMGEN. This analysis was conducted independently of the sponsor.
