Timing for the Resumption of Direct Oral Anticoagulants Following Colorectal Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) is a resection technique for colorectal lesions and early-stage neoplasms that allows for en bloc removal to achieve complete histopathological assessment and decreased risk of residual/recurrent disease and overall obviates the need for invasive surgery to address these lesions. Although colorectal ESD has a favorable safety profile, delayed bleeding can be clinically impactful, requiring transfusions and/or endoscopic intervention, particularly among those on anticoagulation therapy at baseline. Direct oral anticoagulants (DOACs) have garnered increased use over the past several years owing to their ease of use and favorable safety profile. Balancing the risk of bleeding with the risk of thromboembolic events while DOAC therapy is on hold is crucial; however, there unfortunately are varying societal guidelines as to when to resume DOAC therapy after ESD.

Ichita et al performed a retrospective cohort study that included patients on DOAC therapy throughout Japan who underwent single-session ESD of colorectal lesions. Patients were then stratified into early-resumption (1 day after ESD) or delayed-resumption (2–3 days after ESD) groups, with the primary outcome being occurrence of delayed bleeding (defined as requiring blood transfusion or endoscopic intervention) or thromboembolic events (cerebral infarction, myocardial infarction, pulmonary embolism, or deep vein thrombosis) within 30 days of the ESD. Furthermore, in order to address selection bias and potential group imbalance, inverse probability of treatment weighting was employed in which each patient was weighted by the stabilized inverse probability of being in the observed group.

Over the course of nearly 11 years, 165,071 non-DOAC users and 3550 DOAC users were identified, with 76% of the DOAC users belonging to the early-resumption group. Patients on DOAC therapy tended to be older and comprised a higher proportion of males than the non-DOAC users. During the 30-day follow-up, the DOAC users had a 3.5-times higher incidence of delayed bleeding and 4.9-times higher incidence of thromboembolic events than the non-DOAC users. Additionally, the median onset of delayed bleeding was later in the DOAC users. After inverse probability of treatment weighting analysis, early resumption in DOAC therapy showed no statistically significant increase in delayed bleeding; however, it was significantly associated with reduced thromboembolic events as compared with delayed resumption. Apixaban was associated with the lowest risk of bleeding, whereas dabigatran had the highest risk. There are a few study limitations that warrant mention. The study was a retrospective review with a possibility of introducing unmeasured confounders and/or selection bias. Additionally, lesion size and performance of ESD closure were variables that were not collected.

In order to address the ambiguity in societal and international guidelines regarding timing of DOAC resumption after ESD, this was a national, observational study to describe the incidence of bleeding and thromboembolic events in patients on DOAC therapy undergoing colorectal ESD stratified by early or late resumption post-ESD. This study shows that resuming DOACs the day after ESD is associated with a reduction in thromboembolic events without significantly increasing the risk of bleeding. Furthermore, the risk of delayed bleeding is dependent on the DOAC type, with dabigatran having the highest association.