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

Abstract

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.