Use of the erythropoesis-stimulating agent (ESA) darbepoetin alfa is linked to increased stroke risk in anemic patients with diabetes and chronic kidney disease (CKD), a new study confirms.

Investigators led by Marc A. Pfeffer, MD, of Brigham and Women’s Hospital in Boston, sought to replicate results of the Trial to Reduce Cardiovascular Events with Aranesp (TREAT) by looking at stroke risk in similar patients. Within Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF), also a double-blind, randomized, and placebo-controlled trial, the researchers identified 816 (of 2,278) systolic heart failure patients with diabetes and CKD.

The stroke rate was 2.3 per 100 persons per year in TREAT-like RED-HF patients receiving darbepoetin alfa compared with 1.1 in patients receiving placebo, according to results published in European Journal of Heart Failure. When data was combined with TREAT for a total of 4,854 diabetic CKD patients, the investigators observed almost twice the stroke risk, but no increased mortality overall, among patients receiving darbepoetin alfa.

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“This inclusion of 816 patients from the heart failure trial RED-HF adds 32 additional strokes to the 154 events in the 4,038 TREAT experience and provides greater power to confirm further the increased stroke risk seen in patients with diabetes and CKD who receive an ESA,” the investigators explained.

Stroke was the only increased hazard associated with the ESA between the two trials. The researchers urged: “This hazard must be considered when deciding whether or not to use ESAs to treat anaemic patients with diabetes and CKD.”  

The investigators could not rule out the possibility that platelet reactivity or greater blood viscosity leading to sheer stress played a role in stroke risk. Iron deficiency itself also has been linked to increased risk during ESA treatment.


  1. Bello, NA; Lewis, EF; Desai, AS; et al. European Journal of Heart Failure; doi: 10.1002/ejhf.412.