Authors' objectives:

The aim of this review is to assess the relative effectiveness, patient acceptability, costs and cost-effectiveness of four strategies for the prevention of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal (GI) toxicity: (1) Cox-1 NSAIDs plus histamine-2 receptor antagonist (H2RA), (2) Cox-1 NSAIDs plus proton pump inhibitors (PPIs), (3) Cox-1 NSAIDs plus misoprostol, and (4) Cox-2 NSAIDs (later expanded to 4a Cox-2 coxibNSAIDs and 4b Cox-2 preferential NSAIDs).

Authors' results and conclusions: Of 118 selected trials, including 125 relevant comparisons (which included 76,322 participants) only 138 deaths and 248 serious GI events were reported. Seven comparisons were judged to be at low risk of bias. Comparing the gastroprotective strategies against placebo, there was no evidence of effectiveness of H2RAs against any primary outcomes (few events reported), PPIs may reduce the risk of symptomatic ulcers [RR 0.09, 95% confidence interval (CI) 0.02 to 0.47], misoprostol reduces the risk of serious GI complications (RR 0.57, 95% CI 0.36 to 0.91) and symptomatic ulcers (RR 0.36, 95% CI 0.20 to 0.67), Cox-2 'preferentials' reduce the risk of symptomatic ulcers (RR 0.41, 95% CI 0.26 to 0.65) and Cox-2 'coxibs' reduce the risk of symptomatic ulcers (RR 0.49, 95% CI 0.38 to 0.62) and possibly serious GI events (RR 0.55, 95% CI 0.38 to 0.80). All strategies except Cox-2 'preferentials' reduce the risk of endoscopic ulcers. There were only 12 direct comparisons between gastroprotective strategies. All they suggest is that Cox-2 preferentials are better than misoprostol for preventing GI complications. Indirect comparisons suggested that PPIs may prevent symptomatic ulcers better than Cox-2 coxibs, but this is very weak evidence. For prevention of endoscopic ulcers PPIs and misoprostol appear more successful than H2RAs and misoprostol is better than Cox-2 preferentials.

Authors' recommendations: Although there is a very large body of evidence comparing Cox-2 NSAIDs with Cox-1 NSAIDs, this is not matched by studies of the other types of gastroprotectors or by studies directly comparing active gastroprotective strategies. This lack of direct comparisons led to the use of indirect comparisons to help understand the relative efficacy of these strategies. Indirect evidence in itself is weak and was also hampered by lack of evidence in the underlying studies (where the gastroprotectors were compared with placebo). Economic modelling suggests that Cox-1 NSAID plus H2RA or Cox-1 NSAID plus PPI are the most cost-effective strategies for avoiding endoscopic ulcers in patients requiring long-term NSAID therapy. All strategies other than Cox-2 selective inhibitors reduce the rate of endoscopic ulcer compared with Cox-1 alone. The economic analysis suggests that there may be a case for prescribing H2RAs in all patients requiring NSAIDs. Misoprostol is more effective, but is associated with a greater cost and GI side-effects which may be unacceptable for patients. However, when assessing serious GI events, the economic analysis is sufficiently weakened by the data available as to render clear practice recommendations impossible. Further large, independent RCTs directly comparing various gastroprotective strategies are needed. These should report items such as major outcomes, primary data, adverse events, assessment of practice and patient preference.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.hta.ac.uk/1300

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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