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Region Hovedstaden - en del af Københavns Universitetshospital
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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

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

DOI

  • Jeroen V Koomen
  • Jasper Stevens
  • George Bakris
  • Ricardo Correa-Rotter
  • Fan Fan Hou
  • Dalane W Kitzman
  • Donald E Kohan
  • Hirofumi Makino
  • John J V McMurray
  • Hans-Henrik Parving
  • Vlado Perkovic
  • Sheldon W Tobe
  • Dick de Zeeuw
  • Hiddo J L Heerspink
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftClinical Pharmacology and Therapeutics
Vol/bind109
Udgave nummer6
Sider (fra-til)1631-1638
Antal sider8
ISSN0009-9236
DOI
StatusUdgivet - jun. 2021

Bibliografisk note

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

ID: 74729529