Greater Epoetin alfa (EPO) doses and short-term mortality risk among hemodialysis patients with hemoglobin levels less than 11 g/dL.
OBJECTIVE
We examined the association between high doses of Epoetin alfa (EPO), which are used to raise and maintain hemoglobin (Hb) levels within target ranges for hemodialysis patients, and short-term mortality risk using multivariable regression and an instrumental variable (IV) analysis.


METHODS
We identified 32 734 patients receiving hemodialysis in 786 facilities from a large US dialysis provider between July 2000 and March 2002 who received care for >4 consecutive months, and had an Hb < 11 g/dL in the third month. We assessed dose titrations following the Hb < 11 g/dL and characterized facilities based on the percentage of patients with dose titrations >25% (instrument). We assessed deaths during the subsequent 90 days and evaluated the EPO dose-mortality association using conventional linear and IV regression.


RESULTS
The study population had a mean (SD) age of 60.4 (15.0) years; 48% were white, 42% were black and 51% were male. In unadjusted analyses, high EPO doses were associated with 90-day mortality risk (Risk Difference, RD = 3.0 per 100 persons, 95%CI:2.3-3.6); mortality risk was attenuated after adjustment for confounding (RD = 1.5 per 100 persons, 95%CI:0.8-2.2) and not associated with high EPO dose in the pooled IV analysis, though confidence intervals (CI) were wide (RD = -0.4 per 100 persons, 95%CI:-3.2-2.4).


CONCLUSIONS
The difference in risk estimates between the adjusted linear regression and the IV regression suggests that the short-term mortality related to EPO dosing may be largely attributable to confounding-by-indication for higher doses. The IV method, which was employed to address the possibility of residual confounding, yielded near null though imprecise effect estimates.
Bradbury
Brian D
BD
Department of Biostatistics and Epidemiology, Amgen, Inc., Thousand Oaks, CA 91320, USA. bradbury@amgen.com
Do
Thy P
TP
Winkelmayer
Wolfgang C
WC
Critchlow
Cathy W
CW
Brookhart
M Alan
MA
D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D015986:Confounding Factors, Epidemiologic; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa