Background: The European Commission requested and funded the Safety Of non-Steroidal anti-inflammatory drugs (SOS) project to assess the cardiovascular and gastrointestinal safety of individual nonsteroidal anti-inflammatory drugs (NSAIDs) and to develop decision models for treatment and regulatory decision-making.
Objectives: To perform a quantitative systematic review of epidemiological studies on the use of individual NSAIDs and the risk of upper gastrointestinal complications (UGIC).
Methods: A total of 2,540 potential studies published between 1980 and 2008 were identified. Of these, 26 studies comparing the risk of UGIC between users and nonusers of NSAIDs were included in the meta-analysis. We estimated pooled relative risks (RR) for each individual NSAID using random-effects models.
Results: RRs ranged from 1.49 (95% CI 1.07–2.08) for celecoxib to 18.45 (10.99–30.97) for azapropazone. RRs were less than 2 for celecoxib and ibuprofen; from 2 to less than 4 for rofecoxib, diclofenac, sulindac, and nimesulide; from 4 to 5 for meloxicam, tenoxicam, ketoprofen, naproxen, diflunisal, and indometacin; and greater than 5 for piroxicam, ketorolac, and azapropazone. High daily doses of NSAIDs were associated with a twofold
to three-fold increased risk. RRs for high doses were 4.70 (2.43–9.09) for ibuprofen, 4.57 (3.67–5.69) for diclofenac, 9.84 (5.68–17.06) for indometacin, 6.56 (4.39–9.79) for naproxen, 8.50 (1.88–38.55) for ketoprofen, and 20.26 (4.14–99.20) for piroxicam.
Conclusions: This is the first meta-analysis of observational studies providing data on selective COX-2 inhibitors.
Celecoxib and ibuprofen had the lowest risk of UGIC. The risk for high-dose ibuprofen was similar to the risk for diclofenac.
