INTRODUCTION: With the increasing use of direct oral anticoagulants (DOACs), managing these agents around endoscopic submucosal dissection (ESD) is crucial. However, due to the need for a large number of cases, studies examining the timing of resumption are lacking, resulting in varied recommendations across international guidelines. We aimed to perform a comparative study about the resumption timing of DOACs after colorectal ESD using a nationwide database in Japan. METHODS: We conducted a retrospective cohort study on colorectal ESD using the Diagnosis Procedure Combination database from 2012 to 2023. Patients using anticoagulants other than DOACs were excluded, and only those who resumed DOACs within 3 days were included. From eligible patients, we divided them into early (the day after ESD) and delayed (2-3 days after ESD) resumption groups. We used inverse probability of treatment weighting to assess the delayed bleeding and thromboembolic events within 30 days. Delayed bleeding was defined as bleeding requiring endoscopic hemostasis or blood transfusion after ESD. RESULTS: Of 176,139 colorectal ESDs, 3,550 involved DOAC users, with 2,698 (76%) categorized as early resumption and 852 (24%) categorized as delayed resumption groups. After inverse probability of treatment weighting adjustment, the early resumption group did not significantly increase delayed bleeding compared with the delayed resumption group (odds ratio 1.05
95% confidence interval 0.78-1.42
P = 0.73). However, it significantly reduced the risk of thromboembolic events (odds ratio 0.45
95% confidence interval 0.25-0.82
P <
0.01). DISCUSSION: Resuming DOACs the day after colorectal ESD was associated with reduced thromboembolic events without significant increase in risk of delayed bleeding.