title: Dose reduction of edoxaban preserves efficacy and safety for the treatment of venous thromboembolism. An analysis of the randomised, double-blind HOKUSAI VTE trial.
abstract: Direct oral anticoagulants simplify venous thromboembolism (VTE) treatment by obviating the need for coagulation monitoring. Nonetheless, renal function, body weight and P-glycoprotein inhibitors influence drug levels. The objective of this analysis was to determine whether reduction in edoxaban dose based on clinical criteria avoids excess drug exposure and preserves efficacy and safety in the Hokusai-VTE study. After initial heparin, patients received edoxaban or warfarin for 3-12 months. Edoxaban was given once daily at a dose of 60 mg, which was reduced to 30 mg in patients with a creatinine clearance of 30-50 ml/minute, body weight ≤60 kg or receiving certain P-glycoprotein inhibitors. The primary efficacy outcome was recurrent VTE and the principal safety outcome was major or clinically relevant non-major bleeding. A total of 8292 patients with acute VTE were randomised, 733 and 719 patients in the edoxaban and warfarin groups met the criteria for dose reduction. These patients were older, more often female or Asian and had more extensive VTE. Edoxaban levels were lower in the 30 mg edoxaban group. Rates of recurrent VTE and bleeding with the 30 mg and 60 mg edoxaban dose were comparable: VTE rates were 3.0 % and 3.2 % and clinically relevant bleeding rates were 7.9 % and 8.6 %, respectively. Rates of recurrent VTE and bleeding in the warfarin-treated patients meeting the criteria for dose reduction were 4.2 % and 12.8 %, respectively. The reduced dose edoxaban regimen maintained efficacy and safety compared with the 60 mg dose but was safer than warfarin in patients meeting the criteria for dose reduction.
authors.affiliation: Peter Verhamme, MD, KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Haemostasis, Leuven, Belgium, Tel.: + 32 16 34 35 32, Fax: + 32 16 34 34 93, E-mail: peter.verhamme@uzleuven.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.forename: Philip S
authors.initials: PS
authors.lastname: Wells
authors.forename: Annelise
authors.initials: A
authors.lastname: Segers
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.forename: Marjolein P A
authors.initials: MP
authors.lastname: Brekelmans
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
authors.forename: Guy
authors.initials: G
authors.lastname: Meyer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Grosso
authors.forename: Gary
authors.initials: G
authors.lastname: Raskob
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
authors.forename: George
authors.initials: G
authors.lastname: Zhang
authors.forename: Harry
authors.initials: H
authors.lastname: Buller
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage* / Q000627:therapeutic use*; D013844:Thiazoles / Q000008:administration & dosage* / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban
keywords: Edoxaban; body weight; dose reduction; renal function; venous thromboembolism