Optimal direct oral anticoagulant for upper gastrointestinal endoscopic submucosal dissection

Abstract

Background: The patients taking direct oral anticoagulants (DOACs) are at high risk for developing ischemic stroke and delayed bleeding in upper gastrointestinal endoscopic submucosal dissection (ESD). We aimed to identify the optimal DOAC based on both adverse events in upper gastrointestinal ESD.

Methods: A retrospective population-based cohort study was conducted using the Diagnosis Procedure Combination database in Japan. We included patients on a DOAC undergoing upper gastrointestinal ESD between 2012 and 2021. The primary outcomes were ischemic stroke occurring after upper gastrointestinal ESD and delayed bleeding in gastroduodenal and esophageal ESD. Inverse probability weightings were applied to balance the four DOAC groups (dabigatran, rivaroxaban, apixaban, and edoxaban), and logistic regression analyses were performed to compare the outcomes.

Results: We analyzed 9729 patients on a DOAC undergoing upper gastrointestinal ESD. Ischemic stroke developed after upper gastrointestinal ESD in 1.4%, 0.7%, 0.6%, and 0.8% of patients taking dabigatran, rivaroxaban, apixaban, and edoxaban, respectively, after weighting. Rivaroxaban and apixaban showed significantly lower risk of ischemic stroke compared with dabigatran (odds ratio, 0.15 and 0.12, respectively) in standard doses. The delayed bleeding developed after gastroduodenal ESD in 7.6%, 14.6%, 19.2%, and 17.3% of patients taking each DOAC, respectively, with the lowest risk in dabigatran, followed by rivaroxaban. A similar pattern was observed in delayed bleeding in esophageal ESD (3.2%, 5.4%, 7.5%, and 5.5% in each DOAC), but with no significant results.

Conclusions: Rivaroxaban might be an optimal DOAC for upper gastrointestinal ESD showing a lower risk for both ischemic stroke and delayed bleeding.

Keywords: Delayed bleeding; Direct oral anticoagulant; Endoscopic submucosal dissection; Ischemic stroke; Rivaroxaban.

Fig. 1

Flow diagram of patient enrollment. GI gastrointestinal, ESD endoscopic submucosal dissection, DOAC direct oral anticoagulant

Fig. 2

Rates of ischemic stroke in upper GI ESD and delayed bleeding in gastroduodenal and esophageal ESD in the four DOACs after IPW. a Rate of ischemic stroke in upper GI ESD. b Rate of delayed bleeding in gastroduodenal ESD. c Rate of delayed bleeding in esophageal ESD. GI gastrointestinal, ESD endoscopic submucosal dissection, DOAC direct oral anticoagulant, IPW inverse probability weighting

Fig. 3

Risk of ischemic stroke in upper GI ESD and delayed bleeding in gastroduodenal and esophageal ESD among the four DOACs. *Statistically sigificant after Holm’s correction.†The significance level after Holm’s correction was set as p < 0.0083. ‡The significance level after Holm’s correction was set as p < 0.010. ¶The significance level after Holm’s correction was set as p < 0.013. §The significance level after Holm’s correction was set as p < 0.017. ^aThe significance level after Holm’s correction was set as p < 0.025. GI gastrointestinal, ESD endoscopic submucosal dissection, DOAC direct oral anticoagulant, OR odds ratio, CI confidence interval

Fig. 4

Risk of ischemic stroke in upper GI ESD and delayed bleeding in gastroduodenal ESD among the four DOACs limited to standard dose. *Statistically sigificant after Holm’s correction. †The significance level after Holm’s correction was set as p < 0.0083. ‡The significance level after Holm’s correction was set as p < 0.010. ¶The significance level after Holm’s correction was set as p < 0.013. §The significance level after Holm’s correction was set as p < 0.017. GI gastrointestinal, ESD endoscopic submucosal dissection, DOAC direct oral anticoagulant, OR odds ratio, CI confidence interval

Fig. 5

Risk of three clinical outcomes among DOACs when patients were limited to no use of heparin. *Statistically sigificant after Holm’s correction. †The significance level after Holm’s correction was set as p < 0.0083. ‡The significance level after Holm’s correction was set as p < 0.010. ¶The significance level after Holm’s correction was set as p < 0.013. §The significance level after Holm’s correction was set as p < 0.017. ^aThe significance level after Holm’s correction was set as p < 0.025. DOAC direct oral anticoagulant, GI gastrointestinal, ESD endoscopic submucosal dissection, OR odds ratio, CI confidence interval