Differences between males and females in risk of NSAID-related severe gastrointestinal events

Pharmacoepidemiol Drug Saf. 1999 Dec;8(7):501-7. doi: 10.1002/(SICI)1099-1557(199912)8:7<501::AID-PDS454>3.0.CO;2-Y.


Purpose: NSAID use has long been established as a risk factor for severe gastrointestinal (GI) events. It is also known that age and gender affect the risk of such events independently of nonsteroidal antiinflammatory drug (NSAID) use. The objective of the present study is to distinguish between gender as an independent risk factor for severe GI events, and the differences between males and females in risk of NSAID-related severe GI events.

Methods: The study design was a nested case-control study. During the study period, 1029 cases were hospitalized with GI bleeds and/or perforations and 14 481 controls without such GI events were selected. Exposure consisted of the number of NSAID prescriptions dispensed by a pharmacy, prior to the data of hospitalization for cases and a corresponding date for controls.

Results: Males have a risk of serious GI events 1.4 times greater than females, independent of NSAID use. However, females have the greater increase in risk of NSAID-related GI events, e.g. at four prescriptions women have an odds ratio (OR) of 7.4 (p<0.05), while men have a corresponding OR of 3.2 (p<0.05). The increasing risk of severe GI events with number of NSAID prescriptions was considerably greater for females than for males, indicating effect-modification. In a stratified analysis by age and gender, it was clear that gender was the greater influence. Various metabolic and epidemiological potential explanations are discussed.

Conclusions: Age and gender are separate risk factors for GI complications as related to NSAID use. Although implied in other studies, the effect of gender on the risk of NSAID-related GI events is clearly stated in this study.