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

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 greater than or equal to50 years (or greater than or equal to40 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 greater than or equal to65, and severe rheumatoid arthritis (1313, 2.3-3.9). Patients administered naproxen who had prior upper GI complications or who were aged greater than or equal to75 years had 1.8.84 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 (1313, 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 greater than or equal to75 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.