1. Medical Technology and Practice Patterns Institute 4733 Bethesda Ave., Suite #510 Bethesda, MD 20814 Phone: 301-652-4005 Fax: 301-652-8335 Comparison of Two Anemia Treatment Strategies Among Elderly Dialysis Patients with Diabetes Thamer M, Zhang Y, Kshirsagar O, Hernán M, Kaufman J, Cotter D Presented at AHRQ Annual Conference September 9-11, 2012, Rockville, MD  Background  Anemia affects nearly all ESRD patients and is associated with reduced quality of life and decreased survival rates  In 1989, FDA approved use of erythropoietin stimulating agents (ESA also known as rHuEPO, epoetin or EPO, trade name EPOGEN®) in treating anemia of renal disease  From 1990 to 2006, the number of persons who initiated ESRD treatment resulting from diabetes increased by 175%  A randomized trial has suggested that ESA therapy targeting higher hematocrit levels might increase the risk of adverse cardiovascular outcomes and mortality in pre-dialysis diabetic patients. The risks associated with different hematocrit treatment strategies among dialysis patients with diabetes are unknown  Objective  To study the risks and benefits of the corrections of anemia to a target of hematocrit (Hct) 34.5-<39.0% as compared with Hct 30.0-<34.5% in ESRD patients Figure 2. Adjusted survival curves. (a) Survival probabilities based on weights truncated at 100. (b) Survival probabilities based on weights truncated at 500. (c). Composite outcomes based on weights truncated at 100. (d) Composite outcomes based on weights truncated at 500. Table 1. Patient characteristics by hematocrit target strategies and diabetic status (N = 35,865)  Statistical Analysis  Fit a pooled logistic model to estimate the probability of mortality and a composite cardiovascular and mortality endpoint based on each treatment strategy  Used inverse-probability (IP) weighted Cox model with strategy assigned at baseline (H-Hct or L-Hct) and baseline risk factors as non-time-varying covariates. Patients are artificially censored when they deviate from their assigned strategy. IP weights of ESA therapy were estimated as a function of previous ESA treatment and time-varying covariates including Hct, iron treatment, hospitalization, and product terms between these variables  Study Design  Data source: USRDS, a national resource that includes demographic and clinical data on ~97% of all US ESRD patients  Patient population: Diabetic and nondiabetic adult U.S. ESRD Medicare hemodialysis patients treated for anemia classified as following a low hematocrit strategy (L-Hct; 30% - <34.5%) or a high hematocrit strategy (H-Hct; 34.5 - <39%)  Outcome measure: mortality and a composite endpoint of mortality and adverse cardiovascular outcomes                                                                        Implications  Morbidity and mortality rates for persons with diabetes and ESRD in the US are unacceptably high. One area for improvement of patient survival is better management of anemia.  Twenty years after the introduction of ESAs to treat anemia, there is still considerable uncertainty in the nephrology community regarding an optimal hematocrit (HCT) target, especially among complex dialysis patients.  Widespread variation exists regarding epoetin dosing protocols and HCT targets among organizations in the U.S. and in Europe.  Tailoring anemia management to complex patients still remains a challenge for the treating physician.  Limitations  Missing treatment-to-treatment data.  Validation of study endpoint using administrative data is problematic.  Analyses depend on the assumption that all confounding factors that affect epoetin dose and HCT level are included in the model.  Conclusion This study suggests that higher hematocrit targets do not lower mortality and cardiovascular risk among elderly hemodialysis patients with diabetes. However, higher hematocrit targets necessitate higher ESA doses which might cause safety concerns. Our study findings support the FDA's most recent advisories recommending a target of less than 33% when treating hemodialysis patients, including those with diabetes. Supported by Agency for Healthcare Research & Quality grant (AHRQ) R21 HS19513. The data reported herein have been supplied by the US Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as the official policy or interpretation of the US government. For additional information please contact: Dennis Cotter Medical Technology and Practice Patterns Institute dcott@mtppi.org dcott@mtppi.org  Results  Compared to L-Hct, hazard ratio (95% CI) associated with H-Hct for diabetics was 1.10 (0.81-1.49) for all-cause mortality and 1.29 (0.88,1.66) for a composite endpoint of death and cardiovascular events.  The adjusted 6-month mortality in H-Hct group were found to be 2% higher than L-Hct among both diabetics and nondiabetics, but was not statistically significant by bootstrap analysis