title: Effect of direct oral anticoagulants on the risk of delayed bleeding after gastric endoscopic submucosal dissection.
abstract: OBJECTIVE
  Anticoagulants are used to prevent thromboembolic events. Direct oral anticoagulants (DOAC) are our new choice; however, their effect on bleeding risk for endoscopic treatment has not been reported. We aimed to assess the clinical effect of DOAC compared to warfarin for gastric endoscopic submucosal dissection (ESD).
  
  
  METHODS
  We retrospectively studied 97 patients on anticoagulants and treated 108 gastric neoplasms with ESD in three referral institutes. Twenty-four patients were taking DOAC, including dabigatran (12), rivaroxaban (11), and apixaban (one) and 73 were taking warfarin.
  
  
  RESULTS
  In the DOAC group, delayed bleeding rate was significantly higher in patients on rivaroxaban than in patients on dabigatran (45% vs 0%, P < 0.05) without relation to heparin bridge therapy (HBT). In the warfarin group, 78% of patients underwent HBT, and delayed bleeding rate was significantly higher in patients with HBT than in those without (36% vs 0%, P < 0.05). Delayed bleeding rate increased as intake of antithrombotic agents increased (P < 0.05). HBT period was shorter (P < 0.05) in DOAC because DOAC achieve the maximum effect quicker, and hospitalization period was shorter (P < 0.05), compared with warfarin. Multivariate analysis showed that HBT (OR, 10.7), rivaroxaban (OR, 6.00) and multiple antithrombotic agents (OR, 4.35) were independent delayed bleeding risk factors.
  
  
  CONCLUSIONS
  The DOAC effect differs in each agent. Dabigatran is a feasible alternative to warfarin for shortening the hospitalization period and decreasing delayed bleeding rate, although rivaroxaban has a significantly higher delayed bleeding risk.
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Toshiyuki
authors.identifier: http://orcid.org/0000-0002-6546-0329
authors.initials: T
authors.lastname: Yoshio
authors.affiliation: Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan.
authors.forename: Hideomi
authors.initials: H
authors.lastname: Tomida
authors.affiliation: Department of Gastroenterology, Osaka National Hospital, Osaka, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Iwasaki
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Horiuchi
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Omae
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Ishiyama
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hirasawa
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yorimasa
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tsuchida
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Fujisaki
authors.affiliation: Department of Gastroenterology, Osaka National Hospital, Osaka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology, Osaka National Hospital, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Mita
authors.affiliation: Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ninomiya
authors.affiliation: Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Michitaka
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Igarashi
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects; D001803:Blood Transfusion / Q000379:methods; D015331:Cohort Studies; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects*; D000069916:Endoscopic Mucosal Resection / Q000009:adverse effects / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019106:Postoperative Hemorrhage / Q000139:chemically induced* / Q000503:physiopathology / Q000628:therapy; D012189:Retrospective Studies; D012307:Risk Factors; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects*; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000473:pathology / Q000601:surgery; D013923:Thromboembolism / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: antithrombotic therapy; delayed bleeding; direct oral anticoagulant; endoscopic submucosal dissection; heparin bridge therapy