Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with an increase in upper gastrointestinal complications. There is no agreement, ho wever, on whether all conventional NSAIDs have a similar relative risk (RR) , and epidemiologic data are Limited on acetaminophen. We studied the assoc iation between these medications and the risk of upper gastrointestinal ble ed/perforation in a population-based cohort of 958,397 persons in the Unite d Kingdom between 1993 and 1998. Our nested case-control analysis included 2,105 cases and 11,500 controls. RR estimates were adjusted for several fac tors known to be associated with upper gastrointestinal bleed/perforation. Compared with non-users, users of acetaminophen at doses less than 2 gm did not have an increased risk of upper gastrointestinal complications. The ad justed RR for acetaminophen at doses greater than 2 gm was 3.6 [95% confide nce interval (95% CI) = 2.6-5.1]. The corresponding RRs for low/medium and high doses of NSAIDs were 2.4 (95% CI = 1.9-3.1) and 4.9 (95% CI = 4.1-5.8) . The RR was 3.1 (95% CI = 2.5, 3.8) for short plasma half-life, 4.5 (95% C i = 3.5-5.9) for long half-life, and 5.4 (95% CI = 4.0-7.1) for slow-releas e formulations of NSAIDs. After adjusting for daily dose, the differences i n RR between individual NSAIDs tended to diminish except for apazone. Users of H-2 receptor antagonists, omeprazole, and misoprostol had RRs of 1.4 (9 5% CI = 1.2-1.8), 0.6 (95% CI = 0.4-0.9), and 0.6 (95% CI = 0.4-1.0), respe ctively. Among NSAID users, use of nitrates was associated with an RR of 0. 6 (95% CI = 0.4-1-0).