title: Risk of bleeding with dabigatran in atrial fibrillation.
abstract: OBJECTIVE
  It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice.
  
  
  OBJECTIVE
  To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data.
  
  
  METHODS
  In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011.
  
  
  METHODS
  Dabigatran users (n = 1302) and warfarin users (n = 8102).
  
  
  METHODS
  We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities.
  
  
  RESULTS
  Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease.
  
  
  CONCLUSIONS
  Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.
authors.affiliation: Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Hernandez
authors.affiliation: Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Seo Hyon
authors.initials: SH
authors.lastname: Baik
authors.affiliation: Department of Obstetrics and Gynecology, La Paz University Hospital, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piñera
authors.affiliation: Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D000991:Antithrombins / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001562:Benzimidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D000069604:Dabigatran; D016208:Databases, Factual; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D006278:Medicare; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D014481:United States; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran