The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review

doi:10.1136/bmj.38232.680567.EB

BMJ 2004;329:948 (23 October), doi:10.1136/bmj.38232.680567.EB (published 8 October 2004)

Primary care

The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review

Lee Hooper, lecturer¹, Tamara J Brown, research associate², Rachel Elliott, clinical senior lecturer³, Katherine Payne, research fellow⁴, Chris Roberts, senior lecturer in medical statistics⁵, Deborah Symmons, professor⁶

¹ Cochrane Oral Health Group, University of Manchester and Central Manchester and Manchester Children's University Healthcare Trust, Manchester Dental Education Centre, University Dental Hospital, Manchester M15 6FH, ² Health Economics Research at Manchester, University of Manchester, ³ School of Pharmacy and Pharmaceutical Sciences, University of Manchester, ⁴ North West Genetics Knowledge Park, Manchester, ⁵ Biostatistics Group, School of Epidemiology and Health Sciences, University of Manchester, ⁶ ARC Epidemiology Unit, University of Manchester

Correspondence to: L Hooper lee.hooper{at}man.ac.uk

Objectives To assess the effectiveness of five gastroprotectivestrategies for people taking non-steroidal anti-inflammatorydrugs (NSAIDs)—H₂ receptor antagonists plus non-selective(or cyclo-oxygenase-1) NSAIDs; proton pump inhibitors plus non-selectiveNSAIDs; misoprostol plus non-selective NSAIDs; COX-2 selectiveNSAIDs; or COX-2 specific NSAIDs—in reducing serious gastrointestinalcomplications, symptomatic ulcers, serious cardiovascular orrenal disease, and deaths, and improving quality of life.

Data sources The Cochrane Library, Medline, Embase, CurrentControlled Trials, and System for Information on Grey Literaturein Europe (SIGLE) were searched to May 2002. Bibliographiesand author contacts were used to identify further studies; non-Englisharticles were included.

Review methods Trial selection, data extraction, and qualityassessment were performed independently, in duplicate. Articleswere rejected only if the study was not a randomised controlledtrial; did not assess a gastroprotective strategy versus placebo;included exclusively children or healthy volunteers; lastedless than 21 days; or no review outcomes were measured. Qualityassessment included allocation concealment and baseline similarity.

Random effects meta-analysis, meta-regression and subgroupingwere used to pool effects and analyse associations with lengthof follow up, mean age, and baseline gastrointestinal status.Heterogeneity was examined and sensitivity analyses performed.

Results Of 112 included randomised controlled trials (74 666participants), five were judged to be at low risk of bias, and138 deaths and 248 serious gastrointestinal events were reportedoverall. On comparing gastroprotective strategies versus placebowe found no evidence of effectiveness of H₂ receptor antagonistsfor any primary outcomes (few events reported); proton pumpinhibitors may reduce the risk of symptomatic ulcers (relativerisk 0.09, 95% confidence interval 0.02 to 0.47); misoprostolreduces the risk of serious gastrointestinal complications (0.57,0.36 to 0.91) and symptomatic ulcers (0.36, 0.20 to 0.67); COX-2selectives reduce the risk of symptomatic ulcers (0.41, 0.26to 0.65) and COX-2 specifics reduce the risk of symptomaticulcers (0.49, 0.38 to 0.62) and possibly serious gastrointestinalcomplications (0.55, 0.38 to 0.80). All strategies except COX-2selectives reduce the risk of endoscopic ulcers (at least 3mm in diameter).

Conclusions Misoprostol, COX-2 specific and selective NSAIDs,and probably proton pump inhibitors significantly reduce therisk of symptomatic ulcers, and misoprostol and probably COX-2specifics significantly reduce the risk of serious gastrointestinalcomplications, but data quality is low. More data on H₂ receptorantagonists and proton pump inhibitors are needed, as is betterreporting of rare but important outcomes.

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