Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation - An overview of epidemiologic studiespublished in the 1990s

Background: In the last decades, studies have estimated the upper gastroint estinal tract bleeding/ perforation (UGIB) risk associated with individual nonsteroidal anti-inflammatory drugs (NSAIDs). Later analyses have also inc luded the effect of patterns of NSAID use, risk factors for UGIB, and modif iers of NSAID effect. Methods: Systematic review of case-control and cohort studies on serious ga strointestinal tract complications and nonaspirin NSAIDs published between 1990 and 1999 using MEDLINE. Eighteen original studies were selected accord ing to predefined criteria. Two researchers extracted the data independentl y. Pooled relative risk estimates were calculated according to subject and exposure characteristics. Heterogeneity of effects was tested and reasons f or heterogeneity were considered. Results: Advanced age, history of peptic ulcer disease, and being male were risk factors for UGIB. Nonsteroidal anti-inflammatory drug users with adva nced age or a history of peptic ulcer had the highest absolute risks. The p ooled relative risk of UGIB after exposure to NSAIDs was 3.8 (95% confidenc e interval, 3.6-4.1). The increased risk was maintained during treatment an d returned to baseline once treatment was stopped. A clear dose response wa s observed. There was some variation in risk between individual NSAIDs, tho ugh these differences were markedly attenuated when comparable daily doses were considered. Conclusions: The elderly and patients with a history of peptic ulcer could benefit the most from a reduction in NSAID gastrotoxicity. Whenever possibl e, physicians may wish to recommend lower doses to reduce the UGIB risk ass ociated with all individual NSAIDs, especially in the subgroup of patients with the greatest background risk.