Stratifying the risk of NSAID-related upper gastrointestinal clinical events: results of a double-blind outcomes study in patients with rheumatoid arthritis

Gastroenterology. 2002 Oct;123(4):1006-12. doi: 10.1053/gast.2002.36013.


Background & aims: Epidemiologic data indicate that the risk of nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) clinical events varies based on patients' clinical characteristics. The authors determined risk factors for NSAID-related clinical upper GI events and the event rates, absolute risk reductions, and numbers needed to treat for individual risk factors for a nonselective NSAID and a selective cyclooxygenase 2 inhibitor in a double-blind outcomes trial.

Methods: Eight thousand seventy-six rheumatoid arthritis patients aged >or=50 years (or >or=40 on corticosteroid therapy) were randomly assigned to rofecoxib 50 mg daily or naproxen 500 mg twice daily for a median of 9 months. The development of clinical upper GI events (bleeding, perforation, obstruction, and symptomatic ulcer identified on clinically indicated work-up) was assessed.

Results: Significant risk factors included prior upper GI events, age >or=65, and severe rheumatoid arthritis (RR, 2.3-3.9). Patients administered naproxen who had prior upper GI complications or who were aged >or=75 years had 18.84 or 14.46 events per 100 patient-years, and the risk of events remained constant over time. The reduction in events with rofecoxib was similar in high- and low-risk subgroups (RR, 0.31-0.68). The number needed to treat with rofecoxib instead of naproxen to avert 1 GI event was 10-12 in highest risk patients (prior event, age >or=75 years, or severe rheumatoid arthritis), 17-33 in patients with other risk factors, and 42-106 in low-risk patients.

Conclusions: NSAID-related GI events increase dramatically with risk factors such as prior events or older age. Ten to twelve high-risk patients need to be treated with a protective strategy such as the selective cyclooxygenase 2 inhibitor, rofecoxib, to avert a clinical GI event.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Age Distribution
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology*
  • Double-Blind Method
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / epidemiology*
  • Helicobacter Infections / epidemiology
  • Helicobacter pylori
  • Humans
  • Lactones / adverse effects*
  • Middle Aged
  • Multivariate Analysis
  • Naproxen / adverse effects
  • Risk Factors
  • Sulfones
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents, Non-Steroidal
  • Lactones
  • Sulfones
  • rofecoxib
  • Naproxen