Individual nonsteroidal antiinflammatory drugs and other risk factors for upper gastrointestinal bleeding and perforation

We conducted a nested case-control study of 1,377 cases of upper gastrointestinal bleeding or perforation (UGIB) and 10,000 controls to evaluate the association of individual nonsteroidal antiinflammatory drugs (NSAIDs), utilization characteristics, and other risk factors for these conditions. Age was the strongest risk factor for UGIB. Male gender, history of complicated peptic ulcer disease, and current use of steroids were also risk factors for UGIB. The adjusted odds ratio (OR) for current NSAID use was 4.3 [95% confidence interval (CI) = 3.7-5.0]. The ORs for current NSAID use were similar for fatal cases and for the gastric, duodenal, prepyloric, and multiple sites of lesion, but the OR was substantially increased for perforations (OR = 16.9; 95% CI = 9.1-31.5). Women age 80 years or older experienced the greatest effect of NSAID use. Current users of multiple NSAIDs and recent switchers showed ORs of 9.0 and 6.2, respectively. Ibuprofen showed the lowest OR and diflunisal, the highest. ORs for low, medium, and high NSAID daily dose were 2.9, 4.2, and 5.8, respectively. This trend was present among new, short-term, and long-term users. Simultaneous use of multiple NSAIDs as well as use of a single individual NSAID at high doses greatly increases the risk of complicated peptic ulcer disease.