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Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease

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Harvard

Koomen, JV, Stevens, J, Bakris, G, Correa-Rotter, R, Hou, FF, Kitzman, DW, Kohan, DE, Makino, H, McMurray, JJV, Parving, H-H, Perkovic, V, Tobe, SW, de Zeeuw, D & Heerspink, HJL 2021, 'Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease', Clinical Pharmacology and Therapeutics, bind 109, nr. 6, s. 1631-1638. https://doi.org/10.1002/cpt.2143

APA

Koomen, J. V., Stevens, J., Bakris, G., Correa-Rotter, R., Hou, F. F., Kitzman, D. W., Kohan, D. E., Makino, H., McMurray, J. J. V., Parving, H-H., Perkovic, V., Tobe, S. W., de Zeeuw, D., & Heerspink, H. J. L. (2021). Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease. Clinical Pharmacology and Therapeutics, 109(6), 1631-1638. https://doi.org/10.1002/cpt.2143

CBE

Koomen JV, Stevens J, Bakris G, Correa-Rotter R, Hou FF, Kitzman DW, Kohan DE, Makino H, McMurray JJV, Parving H-H, Perkovic V, Tobe SW, de Zeeuw D, Heerspink HJL. 2021. Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease. Clinical Pharmacology and Therapeutics. 109(6):1631-1638. https://doi.org/10.1002/cpt.2143

MLA

Vancouver

Author

Koomen, Jeroen V ; Stevens, Jasper ; Bakris, George ; Correa-Rotter, Ricardo ; Hou, Fan Fan ; Kitzman, Dalane W ; Kohan, Donald E ; Makino, Hirofumi ; McMurray, John J V ; Parving, Hans-Henrik ; Perkovic, Vlado ; Tobe, Sheldon W ; de Zeeuw, Dick ; Heerspink, Hiddo J L. / Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease. I: Clinical Pharmacology and Therapeutics. 2021 ; Bind 109, Nr. 6. s. 1631-1638.

Bibtex

@article{5afb52591f2b48c2aa94d5d2a73e17ac,
title = "Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease",
abstract = "Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.",
keywords = "Aged, Area Under Curve, Atrasentan/adverse effects, Diabetes Mellitus, Type 2/complications, Diabetic Nephropathies/complications, Double-Blind Method, Endothelin Receptor Antagonists, Female, Glomerular Filtration Rate, Heart Failure/complications, Humans, Kidney Failure, Chronic/complications, Male, Middle Aged, Treatment Outcome",
author = "Koomen, {Jeroen V} and Jasper Stevens and George Bakris and Ricardo Correa-Rotter and Hou, {Fan Fan} and Kitzman, {Dalane W} and Kohan, {Donald E} and Hirofumi Makino and McMurray, {John J V} and Hans-Henrik Parving and Vlado Perkovic and Tobe, {Sheldon W} and {de Zeeuw}, Dick and Heerspink, {Hiddo J L}",
note = "{\textcopyright} 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.",
year = "2021",
month = jun,
doi = "10.1002/cpt.2143",
language = "English",
volume = "109",
pages = "1631--1638",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "6",

}

RIS

TY - JOUR

T1 - Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease

AU - Koomen, Jeroen V

AU - Stevens, Jasper

AU - Bakris, George

AU - Correa-Rotter, Ricardo

AU - Hou, Fan Fan

AU - Kitzman, Dalane W

AU - Kohan, Donald E

AU - Makino, Hirofumi

AU - McMurray, John J V

AU - Parving, Hans-Henrik

AU - Perkovic, Vlado

AU - Tobe, Sheldon W

AU - de Zeeuw, Dick

AU - Heerspink, Hiddo J L

N1 - © 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

PY - 2021/6

Y1 - 2021/6

N2 - Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.

AB - Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.

KW - Aged

KW - Area Under Curve

KW - Atrasentan/adverse effects

KW - Diabetes Mellitus, Type 2/complications

KW - Diabetic Nephropathies/complications

KW - Double-Blind Method

KW - Endothelin Receptor Antagonists

KW - Female

KW - Glomerular Filtration Rate

KW - Heart Failure/complications

KW - Humans

KW - Kidney Failure, Chronic/complications

KW - Male

KW - Middle Aged

KW - Treatment Outcome

UR - http://www.scopus.com/inward/record.url?scp=85099206375&partnerID=8YFLogxK

U2 - 10.1002/cpt.2143

DO - 10.1002/cpt.2143

M3 - Journal article

C2 - 33338269

VL - 109

SP - 1631

EP - 1638

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 6

ER -

ID: 74729529