title: Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin.
abstract: OBJECTIVE
  Combined anticoagulant and aspirin therapy is associated with increased bleeding risk in patients with atrial fibrillation, but the bleeding risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs) is poorly documented.
  
  
  OBJECTIVE
  To estimate the bleeding risk of combined anticoagulant (rivaroxaban or enoxaparin-vitamin K antagonist [VKA]) and NSAID or aspirin therapy in patients with venous thromboembolism.
  
  
  METHODS
  Prospective analysis of observational data from the EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and clinics in 8246 patients enrolled from 2007 to 2009.
  
  
  METHODS
  Bleeding event rates during exposure to NSAID and aspirin therapy were compared to time without exposure.
  
  
  METHODS
  Days of NSAID or aspirin use and nonuse, clinically relevant bleeding event and major bleeding event rates by patient-years, and hazard ratios.
  
  
  RESULTS
  During NSAID-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 37.5 per 100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID-anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years, compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51-3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]). Major bleeding in aspirin-anticoagulant-treated patients occurred with an event rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA anticoagulation regimens.
  
  
  CONCLUSIONS
  Among patients with venous thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or aspirin is associated with an increased risk of clinically relevant and major bleeding.
authors.affiliation: Division of Pulmonary and Critical Care Medicine,University of Washington School of Medicine, Seattle, Washington.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Davidson
authors.affiliation: University of Amsterdam, the Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Verheijen
authors.affiliation: Bayer Healthcare, Wuppertal, Germany4Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Anthonie W A
authors.initials: AW
authors.lastname: Lensing
authors.affiliation: Bayer Healthcare, Wuppertal, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gebel
authors.affiliation: Haematology Division, Prince of Wales Hospital, Sydney, Australia.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Brighton
authors.affiliation: Cancer Care Centers of South Texas/US Oncology, San Antonio, Texas.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.affiliation: Pulmonary Associates of Fredericksburg, Fredericksburg, Virginia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rehm
authors.affiliation: Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000925:Anticoagulants / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D000069552:Rivaroxaban; D013876:Thiophenes / Q000009:adverse effects; D054556:Venous Thromboembolism / Q000150:complications / Q000188:drug therapy*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D017984:Enoxaparin; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D001241:Aspirin