Stopping anaemia drug better than reducing dose to normalise haemoglobin levels

Discontinuing the anemia drug epoetin may be more effective than reducing the dose for normalising potentially dangerous high haemoglobin levels in haemodialysis patients, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN). The results provide useful information about the balance required between administering epoetin and achieving target haemoglobin levels.

Anaemia is a common complication of chronic kidney disease. Treatment often involves epoetin to boost levels of haemoglobin, the component of blood that transports oxygen throughout the body. Unfortunately, epoetin can increase the risk of heart-related complications and death when used to raise kidney disease patients' haemoglobin levels to what is considered normal in the general population. In addition, kidney disease patients often experience significant fluctuations in haemoglobin levels outside of the recommended range (10 g/dl to 12 g/dl) when using epoetin, which may have a negative impact on health.

Little information is available on the effects of reducing or discontinuing epoetin in patients who develop high haemoglobin levels. To investigate, Daniel Weiner, MD, Jose Calvo, MD (Tufts Medical Center) and their colleagues measured haemoglobin levels over a two month period in 2,789 dialysis patients who discontinued epoetin and 754 dialysis patients who reduced their epoetin dose by 20–30% after developing high haemoglobin levels (13 g/dl or greater). They also explored individual patient characteristics associated with more precipitous drops in haemoglobin level.

Within two months, more patients who discontinued epoetin dropped below 11 g/dl (21.5% vs 10.1%) and 10 g/dl (7.2% vs 3.6%) compared with patients who reduced their epoetin dose. Reducing epoetin was associated with more frequent lowest haemoglobin levels that remained above 12 g/dl (31.1% vs 62.8% of patients), a level higher than that recommended by the FDA.

While discontinuation was associated with a higher likelihood of dropping to a haemoglobin level below 10 g/dl, this occurred in relatively few individuals. Factors associated with a drop in haemoglobin level to below 10 g/dl included higher baseline epoetin dose and elevated blood markers of inflammation. After adjusting for these factors, patients who discontinued epoetin were 1.91 times more likely to have a lowest haemoglobin level below 10 g/dl. In contrast, patients who reduced epoetin were 4.41 times as likely to have a lowest haemoglobin level above 12 g/dl.

These results indicate that once a patient reaches a haemoglobin level of 13 g/dl or higher, discontinuing epoetin is more likely to lower the haemoglobin level to within the recommended range compared with reducing the dose of epoetin. However, discontinuing epoetin also increases the patient's risk of developing a lower-than-recommended haemoglobin level, while reducing epoetin is associated with significantly increased time at a higher-than-recommended haemoglobin level.

The major limitations of the study were the use of administrative data in a retrospective fashion, and the lack of hard outcome data, including mortality. Study co-authors include Dana Miskulin, MD, and Klemens Meyer, MD (Tufts Medical Center).

(Source: American Society Nephrology: Clinical Journal of the American Society Nephrology)