Darbepoetin and risk of stroke

Darbepoetin alfa (Aranesp®) is commonly used in patients with chronic kidney disease and diabetes for the treatment of anemia. A new study suggests that the drug may be associated with increased risk of stroke in this patient population. More than 4000 patients with diabetes, chronic kidney disease, and anemia were randomly assigned to darbepoetin alfa to achieve a hemoglobin level of 13 g/dL or placebo with rescue darbepoetin alfa if hemoglobin levels dropped < 9 g/dL. The primary endpoints were the composite outcomes of death or cardiovascular event, and death or end-stage renal disease. After a follow up of 2.5 years, darbepoetin alfa was ineffective at preventing either primary outcome, and, more importantly, the rate of fatal or nonfatal stroke occurred almost twice as often in the treatment group (101 patients assigned to darbepoetin alfa vs 53 patients assigned to placebo; HR, 1.92; 95% confidence interval, 1.38-2.68; P < 0.001). The authors conclude that the use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who are not undergoing dialysis did not reduce the outcome of death, cardiovascular events, or renal events, but was associated with increased risk of stroke. For many "this risk will outweigh the potential benefits" of the drug (N Engl J Med 2009;361:2019-2032). Erythropoiesis-stimulating agents have come under fire in the treatment of cancer-associated anemia, and now in renal patients as well. As pointed out in an accompanying editorial, the risks and benefits of these agents must be weighed, namely an increased risk of stroke vs a perceived improvement in quality of life (N Engl J Med 2009;361:2089-2090).