A population based nested control analysis1 published in the BMJ has failed to find consistent evidence of enhanced safety against gastrointestinal (GI) events with any of the new cyclo-oxygenase-2 (COX-2) inhibitors compared with non-selective non-steroidal anti-inflammatory drugs (NSAIDs).
This analysis looked at 10,892 cases of upper gastrointestinal events in patients over the age of 25, between August 2000 and July 2004. Each case was matched with up to 10 controls and odds ratios were calculated and adjusted for other NSAIDs, smoking, comorbidity, deprivation, selective serotonin reuptake inhibitors, tricyclic antidepressants, statins, aspirin and ulcer healing drugs.
Overall, there was no strong evidence of a decreased GI risk with the newer COX-2 NSAIDs compared to non-selective NSAIDs. Concurrent use of ulcer-healing drugs reduced the risk of adverse GI events in patients taking COX-2 and non-selective NSAIDs.
Individual analysis of certain NSAIDs demonstrated that ulcer healing drugs in patients taking diclofenac did not alter GI risk, although the authors say this could be due to chance in the data analysed. Also, the interaction between celecoxib and ulcer healing drugs was not significant probably because of the small numbers of patients taking this drug.
The authors of this paper state that as ulcer healing drugs lower the GI risk in patients taking COX-2 NSAIDs that these drugs are not as safe as originally thought. However, all NSAIDs carry a GI risk, the risk with COX-2 selective NSAIDs is lower but not reduced to a baseline level of risk.
Action: This analysis raises again the safety profile of NSAIDs. All NSAIDs carry a GI and cardio-vascular risk, including the newer COX-2 selective NSAIDs. The MHRA advice, as previously covered, applies to all NSAID prescribing:
- Use paracetamol as first line where ever possible
- If necessary, use the NSAID with the lowest overall risk (usually Ibuprofen)
- At the lowest effective dose
- For the shortest period
- And only use one NSAID at a time
- 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. BMJ 2005;331:1310-1316
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