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.
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.


METHODS
Nested case-control study.


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


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Hippisley-Cox
Julia
J
Division of Primary Care, University of Nottingham, Nottingham NG2 7RD. julia.hippisley-cox@nottingham.ac.uk
Coupland
Carol
C
Logan
Richard
R
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004338:Drug Combinations; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006396:Hematemesis / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000139:chemically induced*; D011379:Prognosis; D012307:Risk Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations