| Title | Greater Epoetin alfa (EPO) doses and short-term mortality risk among hemodialysis patients with hemoglobin levels less than 11 g/dL. | | Author(s) | Bradbury BD, Do TP, Winkelmayer WC, Critchlow CW, Brookhart MA | | Institution | Department of Biostatistics and Epidemiology, Amgen, Inc., Thousand Oaks, CA, USA. | | Source | Pharmacoepidemiol Drug Saf 2009 Jul 1. | | 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 (c) 2009 John Wiley & Sons, Ltd. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19572312 |
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