The Relative Efficacies of Gastroprotective Strategies in Chronic Users of Nonsteroidal Anti-inflammatory Drugs

Background & Aims: There are numerous gastroprotective strategies recommended for reducing the risk of upper gastrointestinal (GI) complications in long-term users of nonsteroidal anti-inflammatory drugs (NSAIDs). The relative efficacy of the different strategies alone or in combination is uncertain. Methods: We used the Manitoba Population Health Research Data Repository to perform a population-based matched case-control analysis. All NSAID users (nonselective and cyclooxygenase [COX]-2-specific) users admitted to the hospital with a primary diagnosis for an upper gastrointestinal complication were matched to NSAID-using controls in the community. We used conditional logistic regression analysis to determine the relative efficacy of different gastroprotective strategies (proton pump inhibitors [PPIs], COX-2 inhibitors, and low-dose/high-dose misoprostol) either alone or in combination and to adjust for multiple pertinent covariates. Results: A total of 1382 NSAID/COX-2 users with upper GI complications were matched to 33,957 age- and sex-matched controls. Cotherapy with PPIs or misoprostol or use of a COX-2 inhibitor all significantly reduced the risk of upper GI complications. COX-2 inhibitors were not statistically more likely to prevent upper GI complications than PPIs, although they were superior to low-dose misoprostol. The combination of COX-2 inhibitors with a PPI was associated with the greatest degree of upper GI complication risk reduction. Conclusions: All of the commonly accepted gastroprotective strategies reduce the risk of upper GI complications in NSAID users, although the combination of COX-2 inhibitors with PPIs promotes the greatest risk reduction for NSAID-related upper GI complications. Celecoxib use specifically may be superior to the combination of nonselective NSAIDs with a PPI.