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Greater Epoetin alfa (EPO) doses and short‐term mortality risk among hemodialysis patients with hemoglobin levels less than 11 g/dL
Author(s) -
Bradbury Brian D.,
Do Thy P.,
Winkelmayer Wolfgang C.,
Critchlow Cathy W.,
Brookhart M. Alan
Publication year - 2009
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.1799
Subject(s) - medicine , epoetin alfa , hemodialysis , confidence interval , anemia , population , dialysis , confounding , hemoglobin , proportional hazards model , environmental health
Abstract Purpose 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. Copyright © 2009 John Wiley & Sons, Ltd.