Stopping EPO Bests Dose Reduction for ESRD Patients

Stopping EPO Bests Dose Reduction for ESRD Patients

By Charles Bankhead, Staff Writer, MedPage Today
Published: July 22, 2010
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco. Earn CME/CE credit
for reading medical news
Action Points

* Patients on hemodialysis are more likely to achieve a hemoglobin within the target range if they discontinue an erythropoeisis-stimulating agent rather than have a dose reduction.

* Discontinuation also increases the likelihood of a hemoglobin level that is lower than recommended.

Hemodialysis patients had better hemoglobin profiles when the erythropoiesis-stimulating drug was stopped rather than dose reduced, data from a large cohort study showed.

Twice as many patients achieved a target hemoglobin nadir of <11 g/dL) within two months with discontinuation compared with dose reduction, according to an article published online in the Clinical Journal of the American Society of Nephrology.

However, discontinuation also doubled the likelihood of a hemoglobin nadir <10 g/dL. Conversely, twice as many patients managed by dose reduction had hemoglobin nadirs >12 g/dL or outside the desired target range (10 to 12 g/dL).

Dose reduction also was associated with significantly greater epoetin use compared with discontinuation, wrote Jose Calvo, MD, of Tufts University in Boston, and co-authors.

Several small clinical trials showed that epoetin therapy for anemia reduced transfusion requirements and improved health-related quality of life in patients with late-stage chronic kidney disease and in dialysis patients. However, larger trials evaluating epoetin therapy for normalization of hemoglobin levels either showed no benefit or evidence of potential harm, according to the background.

Cohort data showing harmful effects of marked hemoglobin variability added to growing uncertainty about the optimal anemia management strategy in dialysis patients.

Two different anemia guideline recommendations have been developed. The KDOQI guidelines recommend a target hemoglobin level of 11 to 12 g/dL, whereas the FDA and Centers for Medicare and Medicaid Services specify a target of 10 to 12 g/dL.

Tufts investigators previously showed that a strategy of epoetin dose reduction versus discontinuation resulted in more hemoglobin levels >13 g/dL, fewer levels of 11 to 12.9 g/dL, and no difference in the proportion of values <11 g/dL (J Am Soc Nephrol 2007; 18: 3184-3191).

They continued the investigation by evaluating the effect of dose reduction versus discontinuation on longitudinal changes in hemoglobin levels in dialysis patients with hemoglobin levels ≥13 g/dL.

The analysis included 3,543 hemodialysis patients treated from October 2005 through September 2006, all of whom had hemoglobin levels ≥13 g/dL. Of the total population, 2,789 patients had epoetin discontinued, and 754 had dose reductions of 20% to 30%. The primary outcome was nadir hemoglobin within two months of discontinuation or dose reduction.

Within two months of discontinuation, 21.5% of patients had hemoglobin levels <11 g/dL compared with 10.1% of those who had dose reduction. Additionally, 7.2% of the discontinuation group had hemoglobin levels <10 g/dL within two months compared with 3.6% of patients whose epoetin dose was reduced.

Epoetin dose reduction was associated with nadir hemoglobin levels >12 g/dL in 62.8% of patients versus 31.1% of the discontinuation group.

In multivariate analysis, epoetin discontinuation was associated with an odds ratio of 1.91 for reaching a hemoglobin nadir <10 g/dL, whereas dose reduction quadrupled the odds of a hemoglobin nadir >12 g/dL (OR 4.41).

Calvo reported that he had no disclosures. Several co-authors reported relationships with Dialysis Clinic.

Primary source: Clinical Journal of the American Society of Nephrology
Source reference:
Calvo JA, et al "Nadir hemoglobin levels after discontinuation of epoetin in hemodialysis patients" Clin J Am Soc Nephrol 2010; DOI:10.2215/CNJ.02650310.

http://www.medpagetoday.com/Nephrology/GeneralNephrology/21331