VARIABILITY IN RISK OF GASTROINTESTINAL COMPLICATIONS WITH INDIVIDUALNONSTEROIDAL ANTIINFLAMMATORY DRUGS - RESULTS OF A COLLABORATIVE METAANALYSIS

Objective-To compare the relative risks of serious gastrointestinal co mplications reported with individual non-steroidal anti-inflammatory d rugs. Design-Systematic review of controlled epidemiological studies t hat found a relation between use of the drugs and admission to hospita l for haemorrhage or perforation. Setting-Hospital and community based case-control and cohort studies. Main outcome measures-(a) Estimated relative risks of gastrointestinal complications with use of individua l drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the st udies. Results-12 studies met the inclusion criteria. 11 provided comp arative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks c alculated with exposure to ibuprofen used as reference were all signif icantly greater than 1.0 (interval of point estimates 1.6 to 9.2), Ove rall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam rank ed highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associ ated with relative risks similar to those with naproxen and indomethac in. Conclusions-The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of th e drug used in clinical practice. In higher doses ibuprofen is associa ted with a similar risk to other non-steroidal anti-inflammatory drugs . Use of low risk drugs in low dosage as first line treatment would su bstantially reduce the morbidity and mortality due to serious gastroin testinal toxicity from these drugs.