title: Risk of gastrointestinal adverse effects of dabigatran compared with warfarin among patients with atrial fibrillation: a nationwide cohort study.
abstract: OBJECTIVE
  To examine the risk of gastrointestinal adverse effects associated with dabigatran use compared with warfarin among patients with atrial fibrillation (AF).
  
  
  RESULTS
  Patients with AF and no history of gastrointestinal diseases initiating dabigatran or warfarin were identified from Danish nationwide registries from 22 August 2011 until 31 December 2012. Patients were classified as naive or experienced users, according to prior use of oral anticoagulant (OAC) therapy. The risk of subsequent proton pump inhibitor (PPI) use, upper dyspepsia-like diagnoses (gastroesophageal reflux, gastritis, gastric, and duodenal ulcer) and gastrointestinal bleeding requiring hospitalization, gastroscopy, and discontinuation of dabigatran and warfarin was examined by cumulative incidence rates and multivariable adjusted Cox regression models. We identified five groups: OAC-naive warfarin (n = 4534); OAC-naive dabigatran 110 mg b.i.d. (dabigatran 110) (n = 1168); OAC-naive dabigatran 150 mg b.i.d. (dabigatran 150) (n = 1844); OAC-experienced dabigatran 110 (n = 1143); and OAC-experienced dabigatran 150 (n = 1748). Compared with OAC-naive warfarin, the rate of initiating PPIs was significantly increased for OAC-naive dabigatran 110 [hazard ratio (HR), 1.24; 95% confidence interval (CI), 1.02-1.50]. Other dabigatran regimes were not associated with a higher risk of initiating PPIs, upper dyspepsia-like diagnoses, gastrointestinal bleeding, or gastroscopy. The risk of discontinuation was increased for OAC-experienced dabigatran 150 (HR, 1.13; 95% CI, 1.02-1.25), but not for the other dabigatran-treated groups, relative to OAC-naive warfarin.
  
  
  CONCLUSIONS
  Dabigatran was not associated with upper dyspepsia-like diagnoses or gastrointestinal bleeding requiring hospitalization, and gastroscopy. The risk of subsequent PPI use was increased for OAC-naive dabigatran 110 mg users, and the risk of discontinuation was increased for OAC-experienced dabigatran 150 mg users.
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Niels Andersens Vej 65, 2900 Hellerup, Denmark lailastaerk@gmail.com.
authors.forename: Laila
authors.initials: L
authors.lastname: Staerk
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Niels Andersens Vej 65, 2900 Hellerup, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark The National Institute of Public Health, University of Southern Denmark, Øster Farimagsgade 5A, 1353 Copenhagen K, Denmark.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Gislason
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, Birmingham City Hospital, Dudley Road, Birmingham B18 7QH, UK.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, 2650 Hvidovre, Denmark.
authors.forename: Emil L
authors.initials: EL
authors.lastname: Fosbøl
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Niels Andersens Vej 65, 2900 Hellerup, Denmark.
authors.forename: Morten Lock
authors.initials: ML
authors.lastname: Hansen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2930 Herlev, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Lamberts
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Niels Andersens Vej 65, 2900 Hellerup, Denmark.
authors.forename: Anders Nissen
authors.initials: AN
authors.lastname: Bonde
authors.affiliation: Institute of Health, Science and Technology, Aalborg University, Niels Jernes Vej 12, 9220 Aalborg Ø, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital Gentofte, Niels Andersens Vej 65, 2900 Hellerup, Denmark.
authors.forename: Jonas Bjerring
authors.initials: JB
authors.lastname: Olesen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality*; D015984:Causality; D015331:Cohort Studies; D015897:Comorbidity; D000069604:Dabigatran / Q000009:adverse effects / Q000627:therapeutic use*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000401:mortality*; D006801:Humans; D015994:Incidence; D008297:Male; D012307:Risk Factors; D015996:Survival Rate; D013923:Thromboembolism / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D014859:Warfarin; D000069604:Dabigatran
keywords: Discontinuation; Dyspepsia; Gastrointestinal bleeding; Non-vitamin K antagonist oral anticoagulant; Oral anticoagulation; Proton pump inhibitors