A Perspective article in the NEJM, written by FDA staff members, discusses some of the evidence for use of erythropoiesis-stimulating agents (ESA) in patients with chronic renal disease and suggests that it is time for a re-evaluation of their place in such patients.

The authors note that early trials showed these drugs to have benefits in patients with anaemia of renal disease, however these studies were small and optimal haemoglobin targets have never been established. Subsequent trials aimed to show that increasing haemoglobin levels to the normal range had further benefits, however their results unexpectedly showed poorer clinical outcomes with increased risk of adverse cardiovascular events.

The authors discuss the available trials and note that their interpretation is complex. They comment on possible mechanisms for the increase in cardiovascular events, which may include 'off-target' activity unrelated to effects on erythropoiesis. They suggest that it is time to establish the optimal haemoglobin targets, dosing algorithms and monitoring approach for these patients, and note that the FDA is intending to convene an Advisory Committee meeting during 2010 to discuss these issues.

[Editor's comment: this issue has particular relevance in the USA, where use of ESA in renal patients has generated considerable profit both for the manufacturers and for the for-profit companies running the majority of dialysis services (Lancet 2006; 368: 2191-3).]