Risk of GI Bleed Lower With Selective COX-2 Inhibitors

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Risk of GI Bleed Lower With Selective COX-2 Inhibitors Than With Other

NSAIDs

Laurie Barclay, MD

Sept. 20, 2002 ‹ Two studies published in the Sept. 21 issue of the British

Medical Journal further our understanding of the safety of the selective

cyclo-oxygenase-2 (COX-2) inhibitors, at least with respect to upper

gastrointestinal (GI) hemorrhage.

A systematic review of randomized trials shows that patients taking

celecoxib had significantly fewer adverse GI events than those taking other

nonsteroidal anti-inflammatory drugs (NSAIDs). The second report describes a

retrospective observational study showing that celecoxib and rofecoxib had

less risk of GI hemorrhage than did other NSAIDs, and suggesting that

rofecoxib users were about twice as likely to have an adverse GI event than

celecoxib users.

Because of lack of sufficient data concerning cumulative effects and non-GI

effects, the editorialist recommends reserving these medications for those

at high risk of GI hemorrhage. " Celecoxib is as effective as other NSAIDs

for relief of symptoms of osteoarthritis and rheumatoid arthritis and has

significantly improved GI safety and tolerability, " write J. Deeks,

from the Institute of Health Sciences in Oxford, U.K., and colleagues.

Their systematic literature review, supported in part by Pfizer, identified

nine randomized controlled trials comparing at least 12 weeks of celecoxib

treatment with other NSAID treatment or placebo. In these trials, which

included 15,187 patients with osteoarthritis or rheumatoid arthritis,

celecoxib and other NSAIDs were equally effective as measured by the Western

Ontario and McMaster Universities osteoarthritis index, American College of

Rheumatology responder index, and joint scores for rheumatoid arthritis.

Compared with patients taking other NSAIDs, the rate of withdrawal due to

adverse GI events in patients taking celecoxib was 46% lower (85% confidence

interval [CI], 29%-58%). The incidence of ulcers revealed by endoscopy was

71% lower (95% CI, 59%-79%), and the incidence of symptoms of ulcers,

perforations, bleeds and obstructions was 39% lower (95% CI, 4% to 61%).

" The adoption of selective COX-2 inhibitors has primarily been driven by the

assertion that these drugs cause fewer GI events than do conventional,

non-selective NSAIDs, " write Muhammad Mamdani, from the Institute for

Clinical Sciences in Toronto, Ontario, Canada, and colleagues. Because this

assertion was unproven to date, they conducted a population-based cohort

study to compare the rates of upper GI hemorrhage in over 40,000 NSAID-naive

elderly users of COX-2 inhibitors or other NSAIDs and in a group of 100,000

not using NSAIDs.

Relative to controls, the highest risk of hemorrhage was in users of

non-selective NSAIDs (adjusted rate ratio [ARR] 4.0; 95% CI, 2.3-6.9),

followed by diclofenac plus misoprostol (ARR 3.0; 95% CI, 1.7-5.6), and

rofecoxib (ARR 1.9; 95% CI, 1.3-2.8). Celecoxib use did not increase risk of

GI hemorrhage relative to controls (ARR 1.0; 95% CI, 0.7-1.6).

In an accompanying editorial, , from Guy's, King's, and St.

' School of Medicine in London, U.K., raises methodological issues,

including the absence of rates of death or of cardiovascular events in

either study, and difficulties inherent in viewing COX-2 inhibitors as a

homogeneous group. He notes that the National Institute for Clinical

Excellence suggests that COX-2 inhibitors are perhaps most appropriately

prescribed to patients at high risk for GI hemorrhage.

" More information is ... still required for prescribers to be able to make

rational decisions about the use of these agents, particularly in older

people in whom comorbidity is common and for whom the stakes are high, " he

writes.

BMJ. 2002;325:619-623, 624-627, 607-608