Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case-control study in a new general practice database

Eur J Clin Pharmacol. 2013 Mar;69(3):691-701. doi: 10.1007/s00228-012-1386-3. Epub 2012 Sep 6.

Abstract

Aim: To test the ability a new Spanish primary care research database (BIFAP) to capture the association between upper gastrointestinal bleeding (UGIB) and NSAIDs and other drugs and compare the results with previous studies.

Methods: We performed a nested case-control study in persons aged 40-90 years old included in the period 2001-2005. Potential cases were selected through a computer search followed by an individual blinded review. Controls matched for age, sex and calendar year were randomly selected. The exposure window was defined as 0-30 days before the index date. Adjusted odds ratios were obtained through unconditional logistic regression models.

Results: In a study cohort of 669,115 subjects (1,576,442 person-years) we retrieved 1,193 valid incident cases. Increased risks were found with current use of NSAIDs (RR = 1.72; 95 %CI: 1.41-2.09), metamizole (1.52; 1.09-2.13), low-dose aspirin (1.74; 1.37-2.21), other antiplatelet drugs (1.73; 1.27-2.36), and oral anticoagulants (2.00; 1.44-2.77). We did not find an increased risk with current use of oral corticosteroids (1.11; 0.66-1.86), SSRIs (1.05; 0.77-1.42), or paracetamol (1.00; 0.82-1.23). Acid-suppressing drugs reduced the risk among users of NSAIDs (0.58; 0.39-0.85), particularly in users with antecedents of peptic ulcer (0.16; 0.05-0.58). We detected a decreasing time-trend in the relative risk and the population attributable proportion associated with NSAIDs over the study period.

Conclusions: The increased risk of UGIB associated with NSAIDs was lower than previously reported, which could partly be explained by methodological differences, but a decreasing burden over time of this drug safety problem is suggested. BIFAP has shown to be a valuable tool for pharmacoepidemiological research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems*
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Case-Control Studies
  • Databases, Factual*
  • Drug Interactions
  • Female
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Hemorrhage / epidemiology
  • Gastrointestinal Hemorrhage / prevention & control
  • General Practice*
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Incidence
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Proton Pump Inhibitors / therapeutic use
  • Registries
  • Risk Assessment
  • Risk Factors
  • Spain / epidemiology
  • Time Factors

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors