Edoxaban for the long-term treatment of venous thromboembolism.
Acute treatment and secondary prevention of symptomatic VTE
Evaluation of efficacy and safety of heparin followed by edoxaban versus heparin overlapping with warfarin in patients with DVT and/or PE
Randomized, double-blind phase III non-inferiority study
Active treatment: heparin (LMW heparin s.c. 1 mg/kg twice daily or 1.5 mg/ kg once daily; UFH: 5000 IU bolus i.v., 1300 IU/h continuous infusion, minimum of 5 days and maximum of about 12 days treatment) plus edoxaban for 3-12 months (n=4118)
60 mg p.o. once daily edoxaban (30 mg once daily for patients with creatinine clearance of 30 to 50 ml per minute or a body weight of 60 kg or less or in patients who were receiving concomitant treatment with potent P glycoprotein inhibitors)
Control treatment: heparin as in active treatment plus warfarin
(INR 2.0–3.0) (n=4122)
Primary efficacy endpoint: composite of DVT, non-fatal PE and fatal PE during 12 months, regardless of treatment duration
Secondary efficacy endpoint: composite outcome of symptomatic recurrent DVT, non-fatal recurrent PE and all-cause mortality during 12 months
Principal safety endpoint: major and clinically relevant non-major bleeding during 12 months
8292 patients >18 years with confirmed DVT and/or symptomatic PE
Efficacy outcome: A recurrence of venous thromboembolism during the overall study period occurred in 130 of 4118 patients (3.2%) in the edoxaban group and in 146 of 4122 patients (3.5%) in the warfarin group. Among patients who qualified for the 30-mg dose of edoxaban, recurrent venous thromboembolism occurred in 22 of 733 patients (3.0%) receiving edoxaban, as compared with 30 of the 719 patients (4.2%) receiving warfarin.
Safety outcome: Clinically relevant bleeding (major or nonmajor) occurred in 349 of 4118 patients (8.5%) in the edoxaban group and in 423 of 4122 patients (10.3%) in the warfarin group. Major bleeding occurred in 56 patients (1.4%) in the edoxaban group and 66 patients (1.6%) in the warfarin group. Among patients who qualified for the 30-mg dose of edoxaban, clinically relevant bleeding occurred in 58 of 733 patients (7.9%) who received edoxaban, and in 92 of the 719 patients (12.8%) who received warfarin.
Edoxaban administered once daily after initial treatment with heparin was non-inferior to high-quality standard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism, including those with severe pulmonary embolism
The Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013;369:1406-1415