Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs

doi:10.1136/bmj.325.7365.624

BMJ 2002;325:624 ( 21 September )

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Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs

Editorial by Jones
See also p 619

Muhammad Mamdani, scientist, ^a Paula A Rochon, scientist and assistant director, ^b David N Juurlink, clinical pharmacologist, ^c Alex Kopp, analyst, ^a Geoffrey M Anderson, professor, ^d Gary Naglie, Mary Trimmer chair in geriatric medicine research, ^e Peter C Austin, scientist, ^a Andreas Laupacis, chief executive officer. ^a

^a Institute for Clinical Evaluative Sciences, 2075 Bayview Avenue-G215, Toronto, Ontario, Canada, ^b Kunin Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto, ^c Sunnybrook and Women's College Health Sciences Centre, Toronto, ^d Department of health policy, management, and evaluation, Faculty of Medicine, University of Toronto, ^e University of Toronto

Correspondence to: M Mamdani muhammad.mamdani{at}ices.on.ca

Objective: To compare rates of upper gastrointestinalhaemorrhage among elderly patients given selective cyclo-oxygenase-2(COX 2) inhibitors and non-selective non-steroidal anti-inflammatorydrugs(NSAIDs).
Design: Observational cohortstudy.
Setting: Administrative data from Ontario, Canada,used from 17 April 2000 to 31 March 2001 to identify populationbased, NSAID-naive cohorts ofpatients.
Patients: Subjects aged $>=$ 66 years who started takingnon-selective NSAIDs (n=5391), diclofenac plus misoprostol (n=5087),rofecoxib (n=14 583), or celecoxib (n=18 908) and a randomly selectedcontrol cohort not exposed to NSAIDs (n=100000).
Main outcome measures: Rate ratios of hospital admission for uppergastrointestinal haemorrhage in each drug cohort with adjustmentfor potentialconfounders.
Results: Relative to controls, the multivariate modelrevealed an increased short term risk of upper gastrointestinalhaemorrhage for users of non-selective NSAIDs (adjusted rate ratio4.0 (95% confidence intervals 2.3 to 6.9)), diclofenac plus misoprostol(3.0 (1.7 to 5.6)), and rofecoxib (1.9 (1.3 to 2.8)) but not celecoxib(1.0 (0.7 to 1.6)). Relative to celecoxib, significantly higherrisks of upper gastrointestinal haemorrhage were observed fornon-selective NSAIDs (4.4 (2.3 to 8.5)), diclofenac plus misoprostol(3.2 (1.6 to 6.5)), and rofecoxib (1.9 (1.2 to 2.8)). Relativeto rofecoxib, non-selective NSAID users were at significantlyhigher risk of upper gastrointestinal haemorrhage (1.9 (1.0 to3.5)).
Conclusions: This population based observational studyfound a lower short term risk of upper gastrointestinal haemorrhagefor selective COX-2 inhibitors compared with non-selectiveNSAIDs.

What is already known on this topic
Long term NSAID use is associated with the development of peptic and duodenal ulcers

Selective COX 2 inhibitors are claimed to cause fewer gastrointestinal problems than conventional, non-selective NSAIDs

It is unclear to what degree COX 2 inhibitors increase gastrointestinal risk relative to not using NSAIDs, and the relative gastrointestinal safety of the different COX 2 inhibitors is uncertain

What this study adds
The risk of upper gastrointestinal haemorrhage with the COX 2 inhibitors rofecoxib and celecoxib was significantly lower than with conventional NSAIDs, but the risk with rofecoxib was significantly higher than that with celecoxib

The risk of gastrointestinal haemorrhage with celecoxib was similar to that in controls not using NSAIDs

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