Variability in risk of gastrointestinal complications with different nonsteroidal anti-inflammatory drugs

Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) is known to increase substantially the risk of upper gastrointestinal bleeding and/or perforation. A meta-analysis of the available epidemiologic studies has shown that there are wide differences between individual drugs in the risk of inducing gastrointestinal complications. Of the NSAIDs in common use, ibuprofen and diclofenac were found to be associated with the lowest relative risk; indomethacin, naproxen, sulindac, and aspirin were associated with intermediate risk; and azapropazone, tolmetin, ketoprofen, and piroxicam were associated with higher risk. Some of these apparent differences in toxicity may, however, be dose related. The low risk of gastrointestinal complications associated with ibuprofen appears to be attributable to the low doses that are prescribed routinely in clinical practice. Higher doses of ibuprofen were associated with relative risks similar to those of naproxen and indomethacin. Thus, as first-line treatment, patients should be prescribed the lowest effective dose of an NSAID that appears to be associated with a comparatively low risk. This should substantially reduce the morbidity and mortality from serious gastrointestinal complications that are associated with the use of these drugs.