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Dennis J Cotter

Publications and source records attributed to Dennis J Cotter.

5 recordsLinked to original sources
PubMed2004

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

OBJECTIVE: To evaluate the use of hematocrit as a surrogate end point for survival among end-stage renal disease (ESRD) patients treated with epoetin. STUDY DESIGN AND SETTING: Using United States Renal Data System (USRDS) data, we conducted an observational prospective study to analyze the relationships among epoetin dose, hematocrit, and survival for 31,301 facility-based hemodialysis patients incident to ESRD therapy in 1998. To address our objective, we used criteria developed by Prentice based on results from a Cox regression model. RESULTS: Results indicate that hematocrit is inversely associated with epoetin dose. For the same epoetin treatment-related achieved hematocrit levels, there were widely varying treatment-related survival outcomes, thereby challenging a central criterion required to empirically validate a surrogate end point. CONCLUSION: Our results support earlier clinical trial and epidemiological data suggesting that hematocrit may not be a valid surrogate for survival among the epoetin-treated renal failure population. We hypothesize that hematocrit may not be in the causal pathway or that epoetin may have important mechanisms of action apart from increasing hematocrit. Effective treatment for anemia may therefore not be simply a matter of increasing hematocrit. This study has potential implications for revising the existing treatment guidelines for anemia management and selecting an appropriate treatment regimen.

Dose-Response Relationship, Drug↗
PubMed2004

Epoetin requirements predict mortality in hemodialysis patients.

BACKGROUND: Anemia is a frequent complication of end-stage renal disease. Poor responsiveness to epoetin therapy hampers the management of anemia. Escalating epoetin doses often are used to overcome epoetin resistance. The objective of this study is to examine the relationship between epoetin dose requirements and mortality. METHODS: Using United States Renal Data System administrative claims data, we conducted a retrospective cohort study of 94,569 prevalent hemodialysis patients in 2000 and 2001. A Cox proportional hazard regression analysis, adjusted for baseline variables, and a 5-knot cubic regression spline were used to model the dose-response relationship between epoetin and all-cause mortality. RESULTS: Significant interpatient variation exists in epoetin dose requirements to attain defined hematocrit levels. For every hematocrit cohort studied, patients administered higher doses of epoetin had significantly lower hematocrit values and greater mortality rates. Using the cubic spline function, a significant nonlinear relationship between increased epoetin dose and mortality was found regardless of hematocrit (P < 0.0001), with the steepest increase in relative risk for death found after the 72.5th dose percentile. CONCLUSION: Epoetin dose requirement is an independent predictor of total mortality in hemodialysis patients after adjustment for hematocrit. Poor responders who continue to have low hematocrit values despite the administration of high epoetin doses may not necessarily benefit from more epoetin, but perhaps should be considered for other adjunctive therapies. In contrast to conventional wisdom, this study suggests that epoetin dosing requirements could provide important prognostic information beyond that predicted by hematocrit alone.

Aged↗
PubMedDate not supplied

Improved survival with higher hematocrits: where is the evidence?

The Centers for Medicare and Medicaid Services (CMS) is reviewing Medicare coverage policy for recombinant human erythropoietin (epoetin) therapy. CMS officials are concerned that "Medicare spending on EPO may be higher than necessary without resulting in optimal patient benefit." Approximately 190 end-stage renal disease (ESRD) patients die each day-a mortality rate that has remained essentially unchanged since 1994-despite improvements in the "adequacy of dialysis, vascular access, and anemia management". To date, the evidence cited in support of a survival benefit of epoetin confuses the relationship between treatment response and outcomes with a causal effect of epoetin. A variety of mechanisms may account for a non-causal association between hematocrit and mortality can occur. We conclude that there is no basis for inferring the survival benefits (or detriments) of increasing a patient's hematocrit by adjusting the dosing of epoetin. Furthermore, we note that caution is required in administering large doses of epoetin to unresponsive patients in order to achieve the target hematocrit. A better understanding of the epoetin/survival relationship, well-grounded in science, is needed to provide a basis for CMS to improve its current epoetin policies, and may help to improve patient mortality.

Epoetin Alfa↗