Recurrent venous thromboembolism during anticoagulation with edoxaban or warfarin: A post hoc analysis of the Hokusai-VTE trial.

Introduction: Venous thromboembolism (VTE) may recur during anticoagulation, but the actual rate is not well established. In a post hoc analysis of the Hokusai-VTE trial we evaluated the risk and determinants of recurrent VTE of patients during anticoagulation with heparin, edoxaban or warfarin.

Materials And Methods: The Hokusai-VTE study showed that in VTE patients edoxaban was non-inferior to warfarin with significantly less bleeding. Treatment duration ranged from 3 to 12 months. The recurrent VTE during anticoagulation period was defined as the VTE which occurred from the date of the first to the last dose (+3 days) of study drug.

Results: 147 of 8240 patients (1.8%) had a recurrent VTE during anticoagulant treatment. Median duration of anticoagulation was 267 days. 80 (54%) patients recurred within the first 30 days, 39 of those during heparin lead-in. 23 of 147 patients died of pulmonary embolism (PE) during anticoagulation (case fatality rate 15.6%). 13 of those fatalities (57%) occurred during the first 30 days; 4 of those during heparin lead-in. The recurrence risk was numerically lower in patients assigned to edoxaban compared to those assigned to warfarin, particularly beyond 30 days. We observed a trend towards a higher proportion of men, high NT-proBNP levels and obesity at the time of diagnosis among patients with early recurrence and mortality in particular.

Conclusion: The risk of recurrent VTE and PE-related mortality during the time of anticoagulation is low but noteworthy. Further studies are warranted to sharpen the risk profile of VTE patients in order to improve treatment and reduce mortality.