Darbepoetin alfa is unsafe as well?

Redbloodcells.jpg: hematologist

Darbepoetin alfa is a an erythropoesis stimulating agent marketed under the name Aranesp by AMGEN. It is used for the treatment of anemia ( a lower than normal blood count) as a consequence of renal failure or cancer.

The use of other similar agents has been questioned over the last 2 to 3 years due to studies in both patients with cancer as well as patients with CKD and on dialysis, which demonstrated an increased risk of mortality, which was due in large part to cardiovascular disease particularly stroke.

The debates that occurred due to the outcome of these studies were legendary, due to the counterintuitive findings that suggested treatment to a target normal Hb was dangerous. Yet some learned individuals maintained that the issue was less the target Hb and more the dose of EPO and time required to achieve the target. With higher doses and more steep rises in Hb associated with increased mortality as suggested by secondary analysis of some rather large studies.

The latest study to tackle this prickly topic hails from the New England Journal of Medicine and the conclusion of the investigators of the TREAT study are as follows:

"The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits."

This is quite a blow for proponents of EPO which I must admit includes the vast majority of nephrologists. Deep down at the gut level it just makes sense that replacing a missing hormone such as erythropoetin and returning the blood count to normal should be a good thing. We can identify very specific negative things that occur when the blood count is low we know by observation that quality of life suffers as well as the function of all organs.

Previous studies have demonstrated the use of Aranesp was..

1. More costly than other similar agents.
2. Safe...? infact Amgen the company developing Aranesp released preliminary results of the TREAT study. One of the Headlines went like this "Amgen Announces Top-Line Results Of Trial To Reduce Cardiovascular Events With Aranesp(R) Therapy (TREAT) In CKD Patients With Type-2 Diabetes" Evidently these top line results were that there was no reduction or increased risk of cardiovascular events at that time. Hardly what I would consider a top of the line result.

Despite logic and gut feelings, the writing on the wall is getting very hard to ignore. We should therefore be very cautious and inform our patients that this is still an area under investigation.