To provide comparisons of the risks associated with individual non-steroidal anti-inflammatory drugs (NSAIDS) relative to ibuprofen with regard to gastrointestinal toxicity.

MEDLINE was searched from 1985 to 1994. The bibliographies of previously published meta-analyses were reviewed. Authors of included studies were contacted for further data and asked about unpublished or unlisted work.

Study designs of evaluations included in the review

Controlled epidemiological studies, with measurement and validation of outcomes, comparable controls and control of confounding factors.

Specific interventions included in the review

Ibuprofen compared with other NSAIDS: diclofenac, ketoprofen, piroxicam, azapropazone, aspirin, sulindac, naproxen, indomethacin, diflunisal, fenoprofen, tolmetin.

Participants included in the review

People taking NSAIDs were included. No further details given.

Outcomes assessed in the review

Serious peptic ulcer, defined by upper GI bleeding and perforation.

How were decisions on the relevance of primary studies made?

The author does not state how the papers were selected for the review, or how many of the reviewers performed the selection.

The author does not state that they assessed validity.

The author does not state how data were extracted for the review, or how many of the reviewers performed the data extraction.

How were the studies combined?

Point estimates from individual studies relative to ibuprofen were computed and pooled across all studies for each drug. Separate estimates of risk associated with low/ medium and high drug dosage were pooled for three drugs. Calculation of the comparative toxicity of each agent was undertaken by assigning a score to the rank order of toxicity in individual studies (weighted by sample size). Scores were then added together to provide a rank order of toxicity which best fitted the results obtained from individual studies.

How were differences between studies investigated?

The author does not state how differences between the studies were investigated.

Twelve studies (number of participants not stated) were included.

The overall relative risk of complications with NSAIDs in the included studies are mainly in the range 3.0 to 5.0 which is consistent with the results obtained from other meta-analyses. Calculations of the RRs from individual studies showed a wide variation but a trend of higher values with some NSAIDs over others suggests a genuine difference between the drugs.

Drugs that appeared in two or more studies were included in the summary ranking analysis: ibuprofen achieved the lowest ranking, followed by diclofenac, whereas ketoprofen, piroxicam and azapropazone had the greatest risk of GI toxicity. Aspirin, sulindac, naproxen and indomethacin carried an intermediate risk.

Five of 12 studies provided information about relative toxicity at different doses. Comparisons were made between ibuprofen, indomethacin and naproxen. There was a clear dose-response effect with ibuprofen at high dosage carrying a similar risk to other NSAIDs at high dosage. At lower doses all three drugs carried a much lower risk of GI toxicity.

The low risk of complications seen with ibuprofen in the main analysis relates to the relatively low doses taken by the majority of patients. When used at higher antiinflammatory dosage it carries a similar risk to other agents at equivalent dosage. NSAIDS show much greater variability in their toxicity than in their efficacy. Prescribers and patients need clear information about the advantages and disadvantages of individual agents to enable them to choose the optimum regimen. For first-line treatment, the lowest effective dose of an NSAID with a good safety record should be used, moving to higher doses or a more toxic agent only if the clinical situation demands it. Newer NSAIDs such as selective cyclooxygenase-2 inhibitors, may provide safer antiinflammatory therapy.

Many details are missing from this report of a systematic review. The review question is not very clear and the literature search uses only MEDLINE, which may have led to non-English language studies being missed. Inclusion criteria are not fully set out (no inclusion criteria relate to participants) and details are not given of study selection and data extraction procedures. Validity assessment of included studies was not undertaken. Very few study details are given and only selected summary estimates of risk are given in the paper. There is not enough information given to say whether the author's conclusions follow from the results.

Practice: The author states that for first-line treatment, the lowest effective dose of an NSAID with a good safety record should be used, moving to higher doses or a more toxic agent only if the clinical situation demands it. Newer NSAIDs such as selective cyclooxygenase-2 inhibitors, may provide safer antiinflammatory therapy.

Research: The authors do not state any implications for further research.

1. Henry D, Lim LLY, Garcia Rodriguez LA et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ 1996;312:1563-6.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.