Edoxaban Exposure‐Response Analysis and Clinical Utility Index Assessment in Patients With Symptomatic Deep‐Vein Thrombosis or Pulmonary Embolism

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 signific...

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Bibliographic Details
Published in:CPT: pharmacometrics and systems pharmacology 2016-04, Vol.5 (4), p.222-232
Main Authors: Nyberg, J, Karlsson, KE, Jönsson, S, Yin, OQP, Miller, R, Karlsson, MO, Simonsson, USH
Format: Article
Language:English
Subjects:
Aged
Anticoagulants
Double-Blind Method
Drug Dosage Calculations
Drug dosages
Embolisms
Factor Xa Inhibitors - administration & dosage
Factor Xa Inhibitors - adverse effects
Female
Glycoproteins
Humans
Knowledge
Male
Mortality
Original
Patients
Prevention
Pulmonary Embolism - drug therapy
Pulmonary embolisms
Pyridines - administration & dosage
Pyridines - adverse effects
Risk Assessment
Risk factors
Studies
Thiazoles - administration & dosage
Thiazoles - adverse effects
Thromboembolism
Thrombosis
Venous Thrombosis - drug therapy
Warfarin - administration & dosage
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Summary: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 (Cav) (HRCav) = 0.98 (i.e., change in the HR with every 1 ng/mL increase of Cav); the composite of recurrent DVT and nonfatal PE with HRCav = 0.99; and the composite of recurrent DVT, nonfatal PE, and all‐cause mortality HRCav = 0.98, and all death using maximal edoxaban concentration (Cmax) with HR (Cmax) = 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.
ISSN:2163-8306
2163-8306
DOI:10.1002/psp4.12077