Secondary analysis of the CHOIR trial epoetin-alpha dose and achieved hemoglobin outcomes

Abstract

Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets. We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials. In the 4 month analysis, significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm were unable to achieve target hemoglobin and required high-dose epoetin-alpha. In unadjusted analyses, the inability to achieve a target hemoglobin and high-dose epoetin-alpha were each significantly associated with increased risk of a primary endpoint (death, myocardial infarction, congestive heart failure or stroke). In adjusted models, high-dose epoetin-alpha was associated with a significant increased hazard of a primary endpoint but the risk associated with randomization to the high hemoglobin arm did not suggest a possible mediating effect of higher target via dose. Similar results were seen in the 9 month analysis. Our study demonstrates that patients achieving their target had better outcomes than those who did not; and among subjects who achieved their randomized target, no increased risk associated with the higher hemoglobin goal was detected. Prospective studies are needed to confirm this relationship and determine safe dosing algorithms for patients unable to achieve target hemoglobin.

Figure 1

Cox proportional hazards models for the primary composite end point of death, coronary heart failure hospitalization, stroke, or MI.

Figure 2. Association between epoetin-α dose and primary end point

(a) Among subjects randomized to the low-hemoglobin group in 4-month landmark analysis. (b) Among subjects randomized to the high-hemoglobin group in the 4-month landmark analysis. (c) Among subjects randomized to the low-hemoglobin group in 9-month landmark analysis. (d) Among subjects randomized to the high-hemoglobin group in the 9-month landmark analysis. (The line indicates the log hazard. The bar graph indicates the percent of treatment arm that fell within each dosing interval.)