title: 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.
authors.affiliation: Department of Medicine, The Renal Division, Duke University Medical Center, Durham, North Carolina, USA. szcze001@mc.duke.edu
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Szczech
authors.forename: Huiman X
authors.initials: HX
authors.lastname: Barnhart
authors.forename: Jula K
authors.initials: JK
authors.lastname: Inrig
authors.forename: Donal N
authors.initials: DN
authors.lastname: Reddan
authors.forename: Shelly
authors.initials: S
authors.lastname: Sapp
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Uptal D
authors.initials: UD
authors.lastname: Patel
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Singh
mesh_terms: D000368:Aged; D000740:Anemia / Q000188:drug therapy*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D051437:Renal Insufficiency / Q000188:drug therapy; D012306:Risk; D016896:Treatment Outcome
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa