Hematocrit was not validated as a surrogate end point for survival among epoetin-treated hemodialysis patients

Cotter, Dennis J.; Stefanik, Kevin; Zhang, Yi; Thamer, Mae; Scharfstein, Daniel O.; Kaufman, James S.

doi:10.1016/j.jclinepi.2004.05.002

Cited by 50 publications

(29 citation statements)

References 35 publications

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“…Recently, two observational studies using USRDS data found that patients with greater EPO dose requirements (i.e., doses needed to achieve a given Hb level) had an elevated risk of mortality over 1 yr of follow-up (16,17). More recently, an analysis using dialysis provider data replicated the findings in these studies, but then showed that improved adjustment for confounding and adjusting for changes in Hb levels and EPO doses over time (which indirectly accounts for patient responsiveness and more closely reflects the dynamic dosing paradigm involved in anemia management) resulted in a markedly attenuated mortality risk specifically related to EPO dosing (18).…”

Section: Discussionmentioning

confidence: 99%

Effect of Epoetin Alfa Dose Changes on Hemoglobin and Mortality in Hemodialysis Patients with Hemoglobin Levels Persistently below 11 g/dL

Bradbury

Danese²,

Gleeson³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: The mortality risk associated with attempting to raise hemoglobin (Hb) levels by increasing Epoetin alfa (EPO) doses in hemodialysis patients with persistently low Hb remains poorly understood.Design, setting, participants, & measurements. We included hemodialysis patients from a large dialysis provider between July 2000 and June 2001 who had EPO dose and Hb data for 6 consecutive months, and a mean Hb <11 g/dl in months 4 to 6 (sub-11 period). We identify predictors of EPO dose changes during the sub-11 period; evaluate the proportion of patients achieving a Hb >11 g/dl after the sub-11 period by dose-change categories; and evaluate the association between EPO dose changes and mortality risk.Results: Patients were more likely to receive greater EPO dose increases if they had lower EPO doses, higher Hb levels, or were recently hospitalized. Greater EPO dose increases elevated the likelihood of achieving an Hb >11 g/dl in the subsequent 3 mo. Larger EPO dose changes over the sub-11 period were not associated with an elevated mortality risk, but having an Hb <9 g/dl at the end of that period independent of dose change was associated with mortality risk. We found that patients receiving larger dose changes and whose resulting Hb level remained <9.5 g/dl at the end of the 3 mo were at elevated mortality risk.Conclusions: In patients with persistently low Hb levels, mortality risk was strongly associated with the patient's ability to achieve a hematopoietic response rather than the magnitude of EPO dose titrations.

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Section: Discussionmentioning

confidence: 99%

Effect of Epoetin Alfa Dose Changes on Hemoglobin and Mortality in Hemodialysis Patients with Hemoglobin Levels Persistently below 11 g/dL

Bradbury

Danese²,

Gleeson³

et al. 2009

Clinical Journal of the American Society of Nephrology

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“…These reports along with modifications in reimbursement for erythropoietic agents (15) has led to widespread utilization of erythropoietic agents in dialysis patients. However, the validity of using anemia as an indicator of outcomes in dialysis patients has been revisited because the purported association of anemia with survival in this population is less than conclusive and based on mostly observational or smaller studies (16,17). Some have suggested that the ratio of epoetin ␣ dosing to hematocrit is indicative of underlying comorbidity and inflammation in dialysis patients and may be a better predictor of mortality than hematocrit without adjustment for use of epoetin ␣ (18,19).…”

Section: Discussionmentioning

confidence: 99%

Center Effects in Anemia Management of Dialysis Patients

Fink¹,

Hsu²,

Zhan³

et al. 2007

Journal of the American Society of Nephrology

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This study set out to determine whether there is a center effect on anemia management in hemodialysis patients. The US Renal Data System and Medicare standard analysis files were analyzed. Between-center variation and within-facility correlations in hematocrit values were examined in two separate data sets (years 2000 and 2001) and compared with simulated samples that were composed of random values that assumed no center effect. Mixed-effect models were used to adjust for multiple factors and quantify the within-facility correlation in hematocrit values. Expected hematocrit values were compared in patients who underwent dialysis at poor and superior performing facilities with fixed characteristics including epoetin ␣ dosing. There was a wider center variation in hematocrit for the actual versus simulated data and a coefficient of variation of 4.1% for the former versus 1.7% for the latter, in both years. O ne of the most important advances in dialysis has been the growing emphasis on quality improvement and the establishment of practice guidelines for the care of dialysis patients. The implementation of these guidelines has been monitored closely using clinical performance measures (CPM) that track several intermediate outcomes, including dialysis adequacy, vascular access placement, and anemia (1,2). Despite aggregate improvements in several CPM, there still are significant variations in performance across nations, regions, and networks and among facilities within networks (3). The implication of such variability in outcomes suggests a need for modification of deficient practices in centers that underperform and replication of best practices in facilities that exceed established benchmarks.Center variations in CPM are closely related to the degree to which individuals within the same facility achieve similar results relative to their counterparts at other centers. This withinfacility correlation and the associated between-center variation are referred to as a center effect. The significance of a center effect relates to what it implies about the factors that influence the CPM under examination A detected center effect is the result of center-specific factors that lead to a within-facility correlation in the CPM of interest and is independent of commonly measured inputs that can be altered at the patient level to improve performance for that outcome. The center-specific factors that contribute to the measured center effect often relate to prevailing processes that are particular to each center but may be poorly characterized. Substantial center effects have been reported for dialysis adequacy and vascular access placement, which are distinct from case-mix and patient-specific factors that are known to affect each of these quality indicators (4 -7).It is not known whether there is a center effect related to the anemia management of hemodialysis patients, but it is important to ask this question. A common strategy of providers is to use higher dosages of erythropoietic agents to improve deficiencies in anemia mana...

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“…O bservational studies using the United States Renal Data System (USRDS) show that patients requiring higher doses of epoetin alfa (EPO) are at greater mortality risk (1,2). However, these patients have a higher prevalence of comorbid conditions and other characteristics associated with poorer prognosis (3)(4)(5).…”

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confidence: 99%

“…We demonstrated previously (3) that adjustment for confounding variables available in dialysis provider data but unavailable in USRDS attenuated the EPO dose-mortality association (1,2). Here, we use an MSM to examine the association between EPO dose and mortality, adjusting for time-dependent confounding.…”

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confidence: 99%