A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

Pfeffer, Marc A.; Burdmann, Emmanuel A.; Chen, Chao Yin; Cooper, Mark E.; Zeeuw, Dick de; Eckardt, Kai Uwe; Feyzi, Jan; Ivanovich, Peter; Kewalramani, Reshma; Levey, Andrew S.; Lewis, Eldrin F.; McGill, Janet B.; McMurray, John J.V.; Parfrey, Patrick S.; Parving, Hans Henrik; Remuzzi, Giuseppe; Singh, Ajay K.; Solomon, Scott D.; Toto, Robert D.

doi:10.1056/nejmoa0907845

Cited by 1,885 publications

(1,576 citation statements)

References 28 publications

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“…Risk models in other diabetic populations (TREAT [Trial to Reduce Cardiovascular Events with Aranesp (darbepoetin‐alfa) Therapy]),26 UKPDS [UK Prospective Diabetes Study]27) have yielded results that also highlight the importance of the risk factors we identified, such as prior HF, glycated hemoglobin, age, heart rate, albuminuria, and cardiac arrhythmias 28, 29. Important differences were that these studies either used composite end points28 or only single outcomes29 when examining predictors.…”

Section: Discussionmentioning

confidence: 99%

Role of B‐Type Natriuretic Peptide and N‐Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

Wolsk

Claggett

Pfeffer

et al. 2017

JAHA

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BackgroundNatriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B‐type natriuretic peptide (BNP) and N‐terminal prohormone B‐type natriuretic peptide (NT‐proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus.Methods and ResultsPatients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow‐up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/NT‐proBNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT‐proBNP to best risk models. Overall, BNP and NT‐proBNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77–0.82, P<0.001), cardiovascular death (0.77–0.83, P<0.001), and heart failure (0.84–0.87, P<0.001). BNP or NT‐proBNP alone predicted death as well as all other variables combined (0.77 versus 0.77).ConclusionsIn patients with a recent acute coronary syndrome and type 2 diabetes mellitus, BNP and NT‐proBNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01147250.

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Section: Discussionmentioning

confidence: 99%

Role of B‐Type Natriuretic Peptide and N‐Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

Wolsk

Claggett

Pfeffer

et al. 2017

JAHA

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“…Correcting anemia usually requires erythropoiesis‐stimulating agents (ESAs). However, the use of ESAs to normalize hemoglobin levels has repeatedly been shown to be associated with an increased risk of cardiovascular events and death 2, 3, 4, 5. The use of iron with ESAs is prerequisite for optimal management of anemia in patients with CKD 6.…”

Section: Introductionmentioning

confidence: 99%

Association of Anemia and Iron Parameters With Mortality Among Patients Undergoing Prevalent Hemodialysis in Taiwan: The AIM‐HD Study

Kuo

Hung

Tseng

et al. 2018

JAHA

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BackgroundThe Taiwan Health Insurance Bureau has conducted a bundled payment system for hemodialysis reimbursement since 1995. The maximum dose of erythropoiesis‐stimulating agents allowed by insurance is capped at 20 000 U of epoetin or 100 μg of darbepoetin alfa per month. Nephrologists have avoided the use of high dosages of erythropoiesis‐stimulating agents to achieve a hemoglobin level of 10 to 11 g/dL by iron supplementation. The clinical impact of these policies on patients’ outcomes is unknown. The authors aimed to assess the AIM‐HD (Association of Anemia, Iron parameters, and Mortality among the prevalent Hemodialysis patients) Study in Taiwan.Methods and ResultsThe AIM‐HD study was conducted based on the Taiwan Renal Registry Data System. From 2001 to 2008, the authors enrolled 42 230 patients undergoing hemodialysis who were older than 20 years and had received hemodialysis for more than 12 months. Patient follow‐ups occurred until death or December 31, 2008. During a study period of 8 years, 12 653 (30.0%) patients died. After multivariate adjustment, the authors found that a hemoglobin level <10 g/dL was significantly associated with higher risk for all‐cause and cardiovascular deaths. Moreover, a serum ferritin level between 300 and 800 ng/mL and transferrin saturation value between 30% and 50% were associated with the lowest all‐cause mortality.ConclusionsThe authors recommend avoiding a low hemoglobin level and maintaining serum ferritin between 300 and 800 ng/mL and transferrin saturation between 30% and 50%, which were associated with lower risks of all‐cause mortality among patients undergoing hemodialysis receiving the restricted erythropoiesis‐stimulating agent doses but prompt intravenous iron supplementation in Taiwan.

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“…Patients were randomized to placebo or darbepoetin with dose adjusted to a hemoglobin level of 13.0 g/dL. Although there was a significant difference in the secondary outcome of stroke, there were no significant differences between the 2 groups in terms of the primary end points: time to the composite of all‐cause mortality, stroke, HF, myocardial infarction, or hospitalization for acute myocardial ischemia or the time to the composite of ESRD or all‐cause mortality 13. This study was approved by an institutional review committee, and the participants gave informed consent to participate in TREAT.…”

Section: Methodsmentioning

confidence: 99%

Coronary Artery Disease Is a Predictor of Progression to Dialysis in Patients With Chronic Kidney Disease, Type 2 Diabetes Mellitus, and Anemia: An Analysis of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Sabe

Claggett

Burdmann

et al. 2016

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BackgroundAlthough clear evidence shows that chronic kidney disease is a predictor of cardiovascular events, death, and accelerated coronary artery disease (CAD) progression, it remains unknown whether CAD is a predictor of progression of chronic kidney disease to end‐stage renal disease. We sought to assess whether CAD adds prognostic information to established predictors of progression to dialysis in patients with chronic kidney disease, diabetes, and anemia.Methods and ResultsUsing the previously described Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) population, we compared baseline characteristics of patients with and without CAD. Cox proportional hazards models were used to assess the association between CAD and the outcomes of end‐stage renal disease and the composite of death or end‐stage renal disease. Of the 4038 patients, 1791 had a history of known CAD. These patients were older (mean age 70 versus 65 years, P<0.001) and more likely to have other cardiovascular disease. CAD patients were less likely to have marked proteinuria (29% versus 39%, P<0.001), but there was no significant difference in estimated glomerular filtration rate between the 2 groups. After adjusting for age, sex, race, estimated glomerular filtration rate, proteinuria, treatment group, and 14 other renal risk factors, patients with CAD were significantly more likely to progress to end‐stage renal disease (adjusted hazard ratio 1.20 [95% CI 1.01–1.42], P=0.04) and to have the composite of death or end‐stage renal disease (adjusted hazard ratio 1.15 [95% CI 1.01–1.30], P=0.03).ConclusionsIn patients with chronic kidney disease, diabetes, and anemia, a history of CAD is an independent predictor of progression to dialysis. In patients with diabetic nephropathy, a history of CAD contributes important prognostic information to traditional risk factors for worsening renal disease.

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A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

Cited by 1,885 publications

References 28 publications

Role of B‐Type Natriuretic Peptide and N‐Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

Role of B‐Type Natriuretic Peptide and N‐Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

Association of Anemia and Iron Parameters With Mortality Among Patients Undergoing Prevalent Hemodialysis in Taiwan: The AIM‐HD Study

Coronary Artery Disease Is a Predictor of Progression to Dialysis in Patients With Chronic Kidney Disease, Type 2 Diabetes Mellitus, and Anemia: An Analysis of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

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