Upper gastrointestinal bleeding among users of NSAIDs: a population-based cohort study in Denmark

It is well-known that use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of upper gastrointestinal bleeding (UGIB), but characteristics of the association and quantification of excess risk at the population level require clarification.

All users of nonaspirin prescription NSAIDs in North Jutland County, Denmark during 1991-95 were identified in the regional Pharmaco-Epidemiologic Database. Using the Hospital Discharge Register, all hospitalizations for UGIBs were identified among the 156,138 users of NSAIDs and compared with the number of expected based on the North Jutland population who did not receive NSAID prescriptions.

During periods of NSAID use without use of other drugs associated with UGIB, we observed 365 UGIBs, a number 3.6 times higher than expected (95% CI = 3.3, 4.0). The excess risk varied by sex, type of NSAID and form and route of administration of the NSAID, but not by age at first NSAID prescription or number of prior prescriptions. Risk declined sharply following cessation of use. For ibuprofen and naproxen, there was a clear trend in rising risk by increasing dose, although the lowest doses were also associated with an excess of UGIB. Concurrent use of corticosteroids, anticoagulants and aspirin further increased the risk of UGIB.

All types and formulations of NSAIDs appear to increase the risk of UGIBs, but the effect appear not to be cumulative and diminish rapidly with discontinue of use. Up to 15% of the UGIBs in the entire population of the North Jutland County may be explained by use of this drug.