The CHOIR trial: Target lower hemoglobin levels in patients with anemia and chronic kidney disease [Classics Series]

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1. In patients with anemia and chronic kidney disease, treating with epoetin alfa to a lower hemoglobin target was associated with significantly reduced incidence of the composite event (death, MI, hospitalization for CHF, and stroke).

2. Achieving the lower hemoglobin target required significantly lower doses of epoetin alfa.

Study Rundown: These findings suggest that in patients with anemia and chronic kidney disease, treating with epoetin alfa to a higher hemoglobin target is linked with a significantly higher risk of negative events (i.e., death, MI, hospitalization for CHF, stroke) when compared to a lower target. Moreover, achieving the higher target requires about double the dose of epoetin alfa, which is quite a costly medication. While this study is a multicentre, randomized trial, it was been criticized for its relatively small size, high rates of withdrawal from the study, and the fact that it was not double-blinded.

In sum, treating anemia in patients with chronic kidney disease using epoetin alfa to a lower hemoglobin target (i.e., ≥11.3 g/dL) was associated with a significantly lower risk of composite events compared to a high target (i.e., ≥13.5 g/dL). Significantly lower doses of epoetin alfa are required to achieve the lower hemoglobin target.

Please click to read the study in NEJM

In Depth [randomized, controlled study]: The CHOIR trial, initially published in 2006 in NEJM, was an open-label, randomized study exploring the use of epoetin alfa in treating anemia associated with chronic kidney disease. The trial sought to determine if treating with epoetin alfa to target a higher hemoglobin level (i.e., ≥13.5 g/dL) would improve outcomes when compared to a lower target (i.e., ≥11.3 g/dL). The targets were adjusted partway through the trial, as the initial targets were 13.0-13.5 g/dL for the high-hemoglobin group and 10.5-11.0 g/dL for the low-hemoglobin group. Patients were included if they were at least 18 years of age, had a hemoglobin <11.0 g/dL, and had chronic kidney disease (i.e., GFR 15-50 ml/min/1.73m2 using MDRD). The primary endpoint was the time to a composite of death, myocardial infarction (MI), hospitalization for congestive heart failure (CHF), or stroke.

The study was terminated early in May 2005 at the second interim analysis on the recommendation of the data and safety monitoring board. At that time, a total of 1,432 participants had been enrolled from 130 states from across the United States, with 715 in the high-hemoglobin group and 717 in the low-hemoglobin group. Analyses were based on intention-to-treat, though a total of 549 (38.3%) patients withdrew from the study prematurely. There was a significantly increased risk of composite event in the high-group compared to the low-group (HR 1.34; 95% CI 1.03-1.74). Of note, death (29.3%) and hospitalization for CHF (45.5%) accounted for 74.8% of the composite events. It was also noted that patients in the high-group required almost double the dose of epoetin alfa to achieve the target when compared to the dose required to achieve the low-target.

By Adrienne Cheung, Andrew Cheung, M.D.

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