By Kristina Rebelo
SAN DIEGO -- November 4, 2009 -- According to a study presented here at the American Society of Nephrology (ASN) Renal Week 2009, the risks associated with using darbepoetin alfa in patients with diabetes, chronic kidney disease (CKD), and moderate anaemia far outweigh the potential benefits.
Efficacy and safety results of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) trial, which failed to meet its primary endpoints in reducing death, cardiovascular events/death, or renal events, were presented here on October 30 during a press briefing.
"We tried to reduce morbidity and mortality in patients with CKD, but we did not reduce either, although we did observe fewer patients requiring red blood cell transfusions, but with increased strokes," said lead investigator Marc A. Pfeffer, MD, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts.
"We think our results may indicate that the risk of this therapy outweigh the rather modest benefits."
Stroke is a recognised risk with erythropoiesis-stimulating agents (ESA), and the drug has included a label warning since its approval. However, the risk found in the TREAT trial was far higher than previously known in patients with CKD who were not on dialysis.
The randomised double-blind, placebo-controlled, phase 3 study began in 2004 and included 4,047 patients (57% female; median age, 68 years) with type 2 diabetes, CKD, and anaemia. Patients were randomised to receive either a subcutaneous dose of darbepoetin alfa 0.75 mcg/kg every 2 weeks or placebo.
The aim was for patients to achieve a haemoglobin target level of 13 g/dL and to lower the incidence of death or cardiovascular morbidity (nonfatal myocardial infarction, hospitalisation for myocardial ischaemia, congestive heart failure, or stroke).
Of the patients, 65.2% had a history of prior cardiovascular disease at the time of randomisation.
During a median follow-up of 2.4 years, over 1,200 patients experienced a primary event.
Death or a cardiovascular event occurred in 632 patients assigned to the darbepoetin alfa arm and in 602 patients assigned to the placebo arm (P = .41).
Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and in 618 patients assigned to placebo (P = .29).
Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and in 53 patients assigned to placebo (P < .001).
Red-cell transfusions were given to 297 patients assigned to the darbepoetin alfa and to 496 patients assigned to placebo (P < .001). Only a modest improvement in fatigue was documented by patients in the darbepoetin alfa group as compared with the placebo group.
Funding for this study was provided by Amgen.
[Presentation title: Trial to Reduce Cardiovascular Events With Aranesp Therapy. Abstract 7010]
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