BMJ  2005;331:1310-1316 (3 December), doi:10.1136/bmj.331.7528.1310

Primary care

Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis

¹ Division of Primary Care, University of Nottingham, Nottingham NG2 7RD, ² Division of Epidemiology and Public Health, University of Nottingham

Objective To determine the risk of an adverse upper gastrointestinal event in patients taking different cyclo-oxygenase-2 inhibitors compared with non-selective non-steroidal anti-inflammatory drugs.

Design Nested case-control study.

Setting 367 general practices contributing to the UK QRESEARCH database, spread throughout every strategic health authority and each health board in England, Wales, and Scotland.

Participants Patients aged 25 or more with a first ever diagnosis of an adverse upper gastrointestinal event (peptic ulcer or haematemesis) between 1 August 2000 and 31 July 2004 and up to 10 controls per case matched for age, sex, calendar time, and practice.

Main outcome measures Unadjusted and adjusted odds ratios for adverse upper gastrointestinal events associated with celecoxib, rofecoxib, ibuprofen, diclofenac, naproxen, other selective and non-selective non-steroidal anti-inflammatory drugs, and aspirin.

Results The incidence of adverse upper gastrointestinal events was 1.36 per 1000 person years (95% confidence interval 1.34 to 1.39). We identified 9407 incident cases and 88 867 matched controls. Increased risks of adverse gastrointestinal events were associated with current use of cyclo-oxygenase-2 inhibitors and with conventional non-steroidal anti-inflammatory drugs. Risks were reduced after adjustment for confounders but remained significantly increased for naproxen (adjusted odds ratio 2.12, 95% confidence interval 1.73 to 2.58), diclofenac (1.96, 1.78 to 2.15), and rofecoxib (1.56, 1.30 to 1.87) but not for current use of celecoxib (1.11, 0.87 to 1.41). We found clinically important interactions with current use of ulcer healing drugs that removed the increased risks for adverse gastrointestinal events for all groups of non-steroidal anti-inflammatory drugs except diclofenac, which still had an increased odds ratio (1.49, 1.26 to 1.76).

Conclusion No consistent evidence was found of enhanced safety against gastrointestinal events with any of the new cyclo-oxygenase-2 inhibitors compared with non-selective non-steroidal anti-inflammatory drugs. The use of ulcer healing drugs reduced the increased risk of adverse gastrointestinal outcomes with all groups of non-steroidal anti-inflammatory drugs, but for diclofenac the increased risk remained significant.

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Rapid Responses:

Read all Rapid Responses

Re: Hippisley-Cox et al, Risk of adverse GI outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis

Joe Feczko, MD
bmj.com, 3 Dec 2005 [Full text]

Risk of adverse GI outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs

Bruce J Ella
bmj.com, 4 Dec 2005 [Full text]

Risk of adverse gastrointestinal outcome in patients taking COX-2 selective and non-selective non-steroidal anti-inflammatory drugs: how strong is the evidence?

Bernard G Bannwarth
bmj.com, 4 Dec 2005 [Full text]

Why did you exlude patients at major risk?

Luca Puccetti
bmj.com, 5 Dec 2005 [Full text]

NSAIDs, Cox-2 and Paracelsus. Risks and Benefits are determined by their Dosis and Potencies.

Prof. Enrique J. Sánchez-Delgado, MD
bmj.com, 5 Dec 2005 [Full text]

COX-2 inhibitors were thought of as a 'safe option'

Michael R Lewis, et al.
bmj.com, 6 Dec 2005 [Full text]

Remind us what the RCT evidence tells us about celecoxib again please?

Jonathan L Underhill
bmj.com, 6 Dec 2005 [Full text]

Adverse gastrointestinal outcomes and cyclo-oxygenase-2 inhibitors

Jean-louis MONTASTRUC, et al.
bmj.com, 9 Dec 2005 [Full text]

Study may show that COX-2-selective drugs in higher risk groups are as safe as NSAIDs in lower risk groups

Timothy D Warner, et al.
bmj.com, 9 Dec 2005 [Full text]

Poor headlines

Timothy B Webb
bmj.com, 14 Dec 2005 [Full text]