Stratifying the risk of NSAID-related upper gastrointestinal clinical events: results of a double-blind outcomes study in patients with rheumatoid arthritis.
OBJECTIVE
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.
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology*; D004311:Double-Blind Method; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D016481:Helicobacter Infections / Q000453:epidemiology; D016480:Helicobacter pylori; D006801:Humans; D007783:Lactones / Q000009:adverse effects*; D008875:Middle Aged; D015999:Multivariate Analysis; D009288:Naproxen / Q000009:adverse effects; D012307:Risk Factors; D013450:Sulfones; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen