Background Non steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen are commonly used by patients with rheumatoid arthritis (RA) for pain relief (1). Approximately one in five patients with RA takes daily aspirin for prophylaxis against cardiovascular disease and with an increased recognition of cardiovascular risk in RA, this number is likely to rise. There is concern over the cardiovascular safety of NSAIDS (2) and evidence that combining low-dose aspirin with other NSAIDS increases the risk of upper gastrointestinal bleeding (3).
Objectives This review sought to compare the efficacy of high dose aspirin with ibuprofen for analgesia in patients with RA and the incidence of gastrointestinal side effects.
Methods A structured literature search for articles published between 1960 and 2012 in Medline, Embase and the Cochrane Central Register of Controlled Trials was used to identify randomised controlled trials comparing the two interventions in patients with RA. Studies satisfying predefined inclusion criteria were selected for the review. Data extraction was performed independently by both authors. Outcome measures included pain intensity and joint tenderness at the earliest measure point. For non cross-over studies only, the incidence of epigastric pain and specifically upper gastrointestinal bleeding/ulceration for the length of the trials was recorded and pooled Peto odds ratios calculated. A high incidence of tinnitus was noted in the aspirin groups and this was included as a secondary outcome.
Results A total of 158 trials were identified with the systematic search strategy. After screening and full paper review, ten suitable blinded randomised controlled trials were included in the review. Included studies were published between 1968 and 1990 and six were of a cross-over design. Trial length varied between three weeks to one year. Daily doses of aspirin were higher than commonly used today: between 3.6g to 5g in 24 hours. Doses of ibuprofen varied between 600mg to 3200mg in 24 hours. Subjective pain scores were reported in six trials and “joint counts” measuring joint tenderness were reported in seven. All trials reported no significant difference between interventions for either of these measures at the earliest time point although a meta-analysis for these outcomes was not possible due to insufficient data being provided. Gastrointestinal side effects were higher with aspirin in all trials and meta-analyses of non cross-over studies showed aspirin was associated with an increased risk of epigastric pain (OR 2.75 95% CI 1.75-4.32) and frank upper gastrointestinal ulceration (OR 7.58 95% CI 2.64-21.78). Aspirin was also associated with a significantly greater incidence of tinnitus (OR 5.99 95% CI 4.13-8.70).
Conclusions At doses between 3.6g and 5g in 24 hours, all trials showed no difference between aspirin and ibuprofen for pain relief in RA but aspirin was associated with significantly more side effects. Further randomised controlled trials with patients taking appropriate acid-suppression therapy, comparing aspirin at lower doses with other NSAIDS, may be warranted to better evaluate analgesic effect, side effects and cardiovascular outcomes for patients with RA.
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Acknowledgements Many thanks to Chris J Cates for advise on statistical analysis.
Disclosure of Interest None Declared