Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors

Arch Intern Med. 2005 Jan 24;165(2):189-92. doi: 10.1001/archinte.165.2.189.


Background: Little is known about the risk of upper gastrointestinal (GI) hemorrhage during the concomitant use of warfarin and selective cyclooxygenase (COX)-2 inhibitors. We examined the association between the concomitant use of warfarin and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors in older adults hospitalized for upper GI hemorrhage.

Methods: This nested case-control analysis of multiple linked health care databases conducted over 1 year identified a cohort of patients in Ontario, Canada, who were older than 66 years and continuously prescribed warfarin. Case patients were those admitted to the hospital with upper GI hemorrhage while taking warfarin. We compared their prescription records prior to hospitalization with those of age- and sex-matched controls who were also receiving warfarin (the control-case ratio was 4:1). Odds ratios (ORs) for the risk of hospitalization for upper GI hemorrhage while concomitantly using warfarin and celecoxib, rofecoxib, or nonselective NSAIDs were determined.

Results: During the study period, we identified 98 821 elderly patients continuously receiving warfarin. Of those, 361 (0.3%) were admitted to the hospital with upper GI hemorrhage. After adjusting for other potential confounders, case patients were significantly more likely to be also taking nonselective NSAIDs (OR, 1.9; 95% confidence interval [CI], 1.4-3.7), celecoxib (OR, 1.7; 95% CI, 1.2-3.6), or rofecoxib (OR, 2.4; 95% CI, 1.7-3.6) prior to hospitalization relative to controls.

Conclusions: Patients taking warfarin concomitantly with selective COX-2 inhibitors have an increased risk of hospitalization for upper GI hemorrhage. The risk appears similar to that of patients simultaneously taking warfarin and nonselective NSAIDs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Case-Control Studies
  • Cohort Studies
  • Cyclooxygenase Inhibitors / adverse effects*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Hemorrhage / diagnosis
  • Gastrointestinal Hemorrhage / epidemiology*
  • Humans
  • Incidence
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Ontario / epidemiology
  • Prognosis
  • Registries
  • Risk Assessment
  • Sex Distribution
  • Warfarin / adverse effects*
  • Warfarin / therapeutic use


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Warfarin