Open AccessEdoxaban Exposure‐Response Analysis and Clinical Utility Index Assessment in Patients With Symptomatic Deep‐Vein Thrombosis or Pulmonary Embolism
Author(s) -
Nyberg J,
Karlsson KE,
Jönsson S,
Yin OQP,
Miller R,
Karlsson MO,
Simonsson USH
Publication year - 2016
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12077
Subject(s) - medicine , edoxaban , pulmonary embolism , deep vein , thrombosis , hazard ratio , cardiology , anesthesia , gastroenterology , warfarin , rivaroxaban , atrial fibrillation , confidence interval
Edoxaban exposure‐response relationships from the phase III study evaluating edoxaban for prevention and treatment of venous thromboembolism (VTE) in patients with acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were assessed by parametric time‐to‐event analysis. Statistical significant exposure‐response relationships were recurrent VTE with hazard ratio (HR) based on average edoxaban concentration at steady state (C av ) (HR Cav ) = 0.98 (i.e., change in the HR with every 1 ng/mL increase of C av ); the composite of recurrent DVT and nonfatal PE with HR Cav = 0.99; and the composite of recurrent DVT, nonfatal PE, and all‐cause mortality HR Cav = 0.98, and all death using maximal edoxaban concentration (C max ) with HR (C max ) = 0.99. No statistical significant exposure‐response relationships were found for clinically relevant bleeding or major adverse cardiovascular event. Results support the recommendation of once‐daily edoxaban 60 mg, and a reduced 30 mg dose in patients with moderate renal impairment, body weight ≤60 kg, or use of P‐glycoprotein inhibitors verapamil or quinidine.