title: Analysis of upper gastrointestinal adverse events among patients given dabigatran in the RE-LY trial.
abstract: OBJECTIVE
  Dabigatran is an oral and direct inhibitor of thrombin. In a study of patients with atrial fibrillation (the RE-LY trial), twice as many subjects given dabigatran reported dyspepsia-like symptoms compared with those given warfarin (controls). We analyzed data from this trial to quantify upper gastrointestinal nonbleeding adverse events (NB-UGI AEs).
  
  
  METHODS
  We analyzed the AE database from the RE-LY trial (18,113 subjects) and assigned NB-UGI AEs to 4 groups: those associated with gastroesophageal reflux (GERD), upper abdominal pain and dyspepsia, dysmotility, or gastroduodenal injury. We analyzed frequency, timing, and severity, and clinical variables associated with NB-UGI AEs.
  
  
  RESULTS
  NB-UGI AEs occurred in 16.9% of subjects given dabigatran and in 9.4% of controls (relative risk [RR], 1.81; 95% confidence interval [CI], 1.66%-1.97%; P < .001). Rates of AEs were not associated with the dose of dabigatran. Among subjects with any UGI symptom who were given dabigatran (n = 2045), symptoms were rated as mild in 46.3%, moderate in 44.8%, and severe in 8.9%; these values were similar to those of controls. GERD-associated NB-UGI AEs were most frequent among the 4 groups (compared with controls, RR, 3.71; 95% CI, 2.98%-4.62%; P < .001). Four percent of subjects stopped taking dabigatran because of NB-UGI AEs (most within 3 months of starting therapy), compared with 1.7% of controls (RR, 2.34; 95% CI, 1.90%-2.88%; P < .001). NB-UGI AEs slightly increased risk of major GI bleeding among subjects given dabigatran and controls (6.8% vs 2.3%, P < .001).
  
  
  CONCLUSIONS
  Among patients given dabigatran for atrial fibrillation, NB-UGI AEs are generally mild or moderate; 4% stopped taking the drug over a median of 21.7 months. The greatest increase was in GERD-type NB-UGI AEs. These observations should guide management and prevention strategies.
authors.affiliation: Køge University Hospital and Copenhagen University, Copenhagen, Denmark. peter.bytzer@dadlnet.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Bytzer
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: Sean
authors.initials: S
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Ezekowitz
authors.forename: Stephan
authors.initials: S
authors.lastname: Formella
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reilly
authors.forename: James
authors.initials: J
authors.lastname: Aisenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000009:adverse effects* / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy; D001562:Benzimidazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D000069604:Dabigatran; D004415:Dyspepsia / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran