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The risk of upper GI bleeding and perforation varies among NSAIDs at the doses frequently used in the general population.
The risk of upper GI bleeding and perforation varies among NSAIDs at the doses frequently used in the general population. The risk is greater with the use of drugs that have a long half-life or slow-release formulation or are associated with profound and coincident inhibition of both cyclooxygenase (COX) isozymes.
Mass Gonzlez and colleagues conducted a review of observational studies on NSAIDs and upper GI bleeding and perforation. They calculated pooled relative risk (RR) estimates for specific NSAIDs and verified whether the degree of inhibition of whole blood COX-1 and COX-2 in vitro by average circulating concentrations predict the RR of upper GI bleeding and perforation.
The pooled RR of upper GI bleeding/perforation was 4.50 for traditional NSAIDs (use at low or medium doses was associated with an RR of 2.79, and the summary RR among patients receiving higher doses was 5.36); the RR was 1.88 for coxibs. Lower RRs were observed for ibuprofen, rofecoxib, aceclofenac, and celecoxib; higher RRs were observed for ketorolac and piroxicam. Estimated RRs were 5.63 for naproxen, 5.57 for ketoprofen, 5.40 for indomethacin, 4.15 for meloxicam, and 3.98 for diclofenac.
The authors noted that the findings from epidemiological studies have robust mechanistic support from results obtained in experimental animals.