Rationale—Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): Evolving the management of cardiovascular risk in patients with chronic kidney disease

Mix, T. Christian H.; Brenner, Robert; Cooper, Mark E.; Zeeuw, Dick de; Ivanovich, Peter; Levey, Andrew S.; McGill, Janet B.; McMurray, John J.V.; Parfrey, Patrick S.; Parving, Hans Henrik; Pereira, Brian J.G.; Remuzzi, Giuseppe; Singh, Ajay K.; Solomon, Scott D.; Stehman‐Breen, Catherine; Toto, Robert D.; Pfeffer, Marc A.

doi:10.1016/j.ahj.2004.09.047

Cited by 113 publications

(66 citation statements)

References 49 publications

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“…These adverse outcomes have not been observed uniformly across these studies, and several outcomes have had marginal statistical significance and wide confidence intervals for effect estimates. Current National Kidney Foundation guidelines recommend a target Hb of 11 to 12 g/dl (20), and a large RCT (N ϭ 4000), TREAT, is examining the efficacy of a high-target hemoglobin compared with placebo in type 2 diabetes with CKD (38).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Therapy and Left Ventricular Mass Index in CKD and ESRD Patients

Parfrey¹,

Lauve²,

Latrémouille-Viau³

et al. 2009

Clinical Journal of the American Society of Nephrology

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108

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Background and objectives: The purpose was to evaluate changes in the left ventricular mass index (LVMi) among anemic chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients treated with recombinant human erythropoietin (EPO).Design, setting, participants, & measurements: A systematic review of the literature, reporting LVMi for patients before and after EPO therapy, was performed. The change in LVMi from baseline to the end of treatment was calculated and stratified by severity of anemia at baseline, target hemoglobin (Hb), and stage of kidney disease.Results: Fifteen eligible studies involving 1731 patients were identified. Cohorts with severe anemia at baseline (<10 g/dl), when given EPO using a lower target level (Hb < 12 g/dl or Hct < 36%) experienced significant reductions in LVMi (؊32.7 g/m 2 ; 95% CI: ؊49.4 to ؊16.1, P < 0.05). However, these studies lacked control groups. Cohorts with moderate anemia at baseline showed insignificant changes in LVMi: 5.3 g/m 2 (95% CI: ؊0.8 to 11.3) for patients assigned to a lower target, and ؊6.6 g/m 2 (95% CI: ؊17.2 to 4.0) for patients assigned to a higher target (Hb > 12 g/dl or Hct > 36%). The effect size was similar in direction for both CKD and ESRD cohorts.Conclusions: Aggregated results from multiple studies suggest that in severe anemia conventional Hb targets for EPO therapy are associated with a reduction in LVMi, but that in moderate anemia target Hb above 12 g/dl does not have a significant beneficial impact on LVMi compared with conventional targets.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin Therapy and Left Ventricular Mass Index in CKD and ESRD Patients

Parfrey¹,

Lauve²,

Latrémouille-Viau³

et al. 2009

Clinical Journal of the American Society of Nephrology

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108

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“…Hemoglobin levels and vital signs were assessed every 2 weeks during the titration period and monthly thereafter. The rationale and design, 10 baseline characteristics, 11 and the primary results 9 of the trial have been published. The Trial to Reduce Cardiovascular Events With Aranesp Therapy is registered at http://www.clinicaltrials.gov, unique identifier: NCT00093015.…”

Section: Methodsmentioning

confidence: 99%

Stroke in Patients With Type 2 Diabetes Mellitus, Chronic Kidney Disease, and Anemia Treated With Darbepoetin Alfa

et al. 2011

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on behalf of the TREAT InvestigatorsBackground-More strokes were observed in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) among patients assigned to darbepoetin alfa. We sought to identify baseline characteristics and postrandomization factors that might explain this association. Methods and Results-A multivariate logistic regression model was used to identify baseline predictors of stroke in 4038 patients with diabetes mellitus, chronic kidney disease, and anemia randomized to receive darbepoetin alfa or placebo.To determine whether postrandomization blood pressure, hemoglobin level, platelet count, or treatment dose were responsible for the increased risk related to darbepoetin alfa, we performed a nested case-control analysis (1:10 matching) identifying nonstroke controls with propensity matching. The risk of stroke was doubled with darbepoetin alfa. Overall, 154 patients had a stroke, 101/2012 (5.0%) in the darbepoetin alfa arm and 53/2026 (2.6%) in the placebo arm (hazard ratio 1.9; 95% confidence interval, 1.4 -2.7). Independent predictors of stroke included assignment to darbepoetin alfa (odds ratio 2.1; 95% confidence interval, 1.5-2.9), history of stroke (odds ratio 2.0; 95% confidence interval, 1.4 -2.9), more proteinuria, and known cardiovascular disease. In patients assigned to darbepoetin alfa, postrandomization systolic and diastolic blood pressure, hemoglobin level, platelet count, and darbepoetin alfa dose did not differ between those with and without stroke. Additional sensitivity analyses using maximal values, latest values, or changes over varying periods of exposure yielded similar results. Conclusions-The 2-fold increase in stroke with darbepoetin alfa in TREAT could not be attributed to any baseline characteristic or to postrandomization blood pressure, hemoglobin, platelet count, or dose of treatment. These readily identifiable factors could not be used to mitigate the risk of darbepoetin alfa-related stroke. Clinical Trial Registration-http://www.clinicaltrials.gov. Unique identifier: NCT00093015.

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“…We await the results of TREAT, a global RCT of 4000 predialysis diabetic patients with chronic kidney disease, planned to stop after the occurrence of 1800 cardiovascular events, to provide further evidence on the potential benefit and safety of hemoglobin targets above those currently recommended (Ͻ12 g/dl) (17). Quality adjusted costs of higher targets are extremely expensive (15).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Therapy, Hemoglobin Targets, and Quality of Life in Healthy Hemodialysis Patients

Foley¹,

Curtis²,

Parfrey³

2009

Clinical Journal of the American Society of Nephrology

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Background and objectives: The effects of different hemoglobin targets when using erythropoiesis-stimulating agents on quality of life are somewhat controversial, and predictors of change in quality of life in endstage renal disease have not been well characterized.Design, setting, participants, & measurements: Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 weeks, using epoetin_alfa as primary therapy. Patients and attending physicians were masked to treatment assignment. Quality of life, a secondary outcome, was prospectively recorded using the Kidney Disease Quality of Life (KDQoL) questionnaire at weeks 0, 24, 36, 48, 60, 72, 84, and 96, with prespecified outcomes being fatigue and quality of social interaction.Results: The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr. Mortality was low, reflecting the relatively healthy group enrolled. Of 20 domains within the KDQoL only the prespecified domain of fatigue showed significant change over time between the two groups. Improvement in fatigue scores in the high-target group ranged from 3.2 to 7.9 over time (P ‫؍‬ 0.007) compared with change in the low-target group. Higher body mass index and lower erythropoietin dose at baseline were independent predictors of improvement in multiple KDQoL domains.Conclusions: In relatively healthy hemodialysis patients, normal hemoglobin targets may have beneficial effects on fatigue. Improvement in multiple domains of quality of life is associated with higher body mass index and lower erythropoietin requirements.

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Rationale—Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): Evolving the management of cardiovascular risk in patients with chronic kidney disease

Cited by 113 publications

References 49 publications

Erythropoietin Therapy and Left Ventricular Mass Index in CKD and ESRD Patients

Erythropoietin Therapy and Left Ventricular Mass Index in CKD and ESRD Patients

Stroke in Patients With Type 2 Diabetes Mellitus, Chronic Kidney Disease, and Anemia Treated With Darbepoetin Alfa

Erythropoietin Therapy, Hemoglobin Targets, and Quality of Life in Healthy Hemodialysis Patients

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