Relationship between Epoetin Alfa Dose and Mortality

Wang, Ouhong; Kilpatrick, Ryan D.; Critchlow, Cathy W.; Liu, Xiang; Bradbury, Brian D.; Gilbertson, David T.; Collins, Allan J.; Rothman, Kenneth J.; Acquavella, John F.

doi:10.2215/cjn.03040509

Cited by 35 publications

(32 citation statements)

References 25 publications

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“…Zhang et al [8] analyzed elderly hemodialysis patients and reported that relative to doses between 20,000 and 30,000 IU/week, relative hazards for other doses were less than 1, although they lacked statistical significance. Wang et al [10] analyzed adult patients receiving hemodialysis from a single provider and reported that relative to doses between 0 and 7,000 IU/week during a 2-week period, the relative hazard for no EPO was 1.72 and that hazard ratios for larger doses were almost 1. These studies and the current study cannot be easily reconciled.…”

Section: Discussionmentioning

confidence: 99%

“…Misspecification of the model of ESA dose may be relevant. Wang et al [10] specified an ordinal logistic regression model of dose, categorized as none or by quartile. This model supposes homogeneity of predictors of administration and dose (given administration), but we found marked differences in these sets of predictors.…”

Section: Discussionmentioning

confidence: 99%

“…Several observational studies have assessed the association of epoetin alfa (EPO) dose with mortality risk in end-stage renal disease (ESRD) patients [5,6,7,8,9,10]. Interpretation of these studies is difficult because EPO dose was non-randomized.…”

Section: Introductionmentioning

confidence: 99%

“…Inadequate control of time-varying confounding may result in biased exposure effect estimates. Two studies have controlled such confounding, but both included relatively small sample sizes [8,10]. …”

Section: Introductionmentioning

confidence: 99%

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Association of Mean Weekly Epoetin Alfa Dose with Mortality Risk in a Retrospective Cohort Study of Medicare Hemodialysis Patients

2011

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Background/Aims: Randomized trials of hemoglobin targeting in chronic kidney disease suggest that erythropoiesis-stimulating agent (ESA) dosing increases mortality risk, but dosing intensity is confounded by hemoglobin concentration. Appropriately designed observational studies are needed to clarify the association of ESA dosing with mortality risk. Methods: Using Medicare claims, we conducted a retrospective cohort study of mortality risk associated with epoetin alfa (EPO) dosing in prevalent hemodialysis patients (n = 137,918), 2000–2004. We used marginal structural modeling to account for time-varying confounding attributable to recent history of blood transfusion and catheter insertion for vascular access, hemoglobin, hospital admission and days, and intravenous iron dosing. We stratified mortality analyses according to hemoglobin level (<10, 10–10.9, 11–11.9, and ≧12 g/dl). Results: With adjustment for serial correlation in EPO dosing, hemoglobin, hospital admission and days, and intravenous iron administration were the strongest predictors of outpatient EPO dosing. With hemoglobin <10 g/dl, mean weekly EPO dose in a 3-month period was negatively associated with subsequent mortality risk. With hemoglobin 10–10.9 and 11–11.9 g/dl, EPO dose and mortality risk were associated in a U-shaped form. With hemoglobin ≧12 g/dl, mean weekly EPO dose >20,000 IU was positively associated with mortality risk. Conclusions: ESA dosing may be directly associated with risk of death, but the nature of the association likely varies according to hemoglobin concentration. Small doses with hemoglobin ≤12 g/dl and large doses with hemoglobin ≧10 g/dl may both be associated with poor outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association of Mean Weekly Epoetin Alfa Dose with Mortality Risk in a Retrospective Cohort Study of Medicare Hemodialysis Patients

2011

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“…21,22 Furthermore, not all studies implicate ESA exposure in explaining risk; a recent study using marginal structural modeling failed to report an association between high ESA dosage and adverse outcome. 23 Conversely, a secondary analysis of the CHOIR study, using landmark analysis as a way to avoid some of the biases inherent in observational studies, demonstrated that high ESA dosage was an independent predictor of the combined end point of mortality, nonfatal MI, heart failure, and stroke. 17 In this analysis, targeting a higher Hb or lower Hb with higher dosages of ESA associates with poor outcomes, whereas achieving a higher Hb improves outcomes.…”

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confidence: 99%