Follow FDA label

In an interview, Dr. Singh, noted: “At this point, we should default in the direction of safety. My recommendation would be to follow the FDA label, namely to avoid targeting a hemoglobin level beyond 12 g/dL.”

 


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He added that it remains unclear whether the greater health risks associated with the targeting of a higher hemoglobin level are due to the higher hemoglobin levels or the use of a higher dose of epoetin alfa. This requires further study.

 

In the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial, Tilman B. Drueke, MD, of Necker Hospital in Paris, and his colleagues enrolled 603 patients with an estimated glomerular filtration rate of 15-35 mL/min per 1.73 m2 and mild-to-moderate anemia.

 

The investigators randomly assigned patients to one of two groups based on target hemoglobin levels to be achieved with epoetin alfa: 13-15 g/dL (normal range, group 1) and 10.5-11.5 g/dL (subnormal range, group 2). The primary end point was a composite of eight cardiovascular events. Secondary end points included left ventricular mass index, quality-of-life scores, and CKD progression.

 

During the three-year study, complete correction of anemia did not affect the risk of a first cardiovascular event: 58 events occurred in group 1 and 47 events occurred in group 2, a statistically insignificant difference. Left-ventricular-mass index remained stable in both groups.

 

More patients in high-target-level group 1 than group 2 required dialysis, although patients in group 1 experienced significant improvements in general health and physical function compared with group 2. The investigators observed no significant difference between the two groups in the combined incidence of adverse events, but hypertensive episodes and headaches were more common in group 1.

 

The investigators concluded that the CREATE study “adds direct evidence to confirm the current best practice guidelines, which recommend partial correction of anemia and not routine normalization of hemoglobin levels.”

 

Present guidelines incomplete

In an accompanying editorial (pp. 2144-2146), Giuseppe Remuzzi, MD, and Julie R. Ingelfinger, MD, observed: “Taken together, these two studies suggest caution in the full correction of anemia in patients with chronic kidney disease…Although we need more information about the ideal target level and should consider the present guidelines incomplete, it seems wisest to refrain from complete correction of anemia in persons with chronic kidney disease.”

 

The editorialists said the most surprising finding “is that high target hemoglobin levels did not ameliorate left ventricular hypertrophy in the CREATE study and, indeed, they increased the risk of congestive heart failure in both trials. Secondary fluid retention and high blood pressure, related to worsening renal function, might explain this finding, at least in part.”

 

The K/DOQI committee plans to reconvene its anemia work group to review the results from CHOIR and CREATE, reports Dr. Singh, associate professor of medicine at HarvardMedicalSchool in Boston and a member of the Renal & Urology News editorial advisory board. He said he and his colleagues are conducting post hoc analyses of CHOIR.

 

In an interview, Dr. Singh says he believes a narrower hemoglobin range should be applied to both dialysis and pre-dialysis pa-tients with anemia, even though the CHOIR study looked only at pre-dialysis patients. The K/DOQI committee and the FDA considered aggregate data on both groups and disseminated guidelines for target hemoglobin levels for all CKD patients, he pointed out. Additionally, data from some dialysis patient studies have suggested an increased risk associated with higher hemoglobin targets.