Background: Proton pump inhibitors (PPIs) are often prescribed to prevent gastrointestinal (GI) events due to non-steroidal anti-inflammatory drugs (NSAIDs) in patients requiring long-term NSAIDs therapy. Are PPIs suitable to prevent GI events due to NSAIDs?
Methods and findings: A narrative review of PPIs, histamine-2 receptor antagonists (H2RAs), misoprostol, and rebamipide was conducted. PPIs prevent upper GI events due to NSAIDs and its evidence is the strongest. However, many articles showed that PPIs were independent risk factor for small intestinal injury or exacerbated NSAIDsinduced small intestinal injury. Moreover, based on metaanalysis, PPIs cause Clostridium difficile infection, fracture, fall, pneumonia (either community or hospital acquired), cardiovascular events and deaths, chronic kidney disease, acute kidney injury, etc. Standard doses of H2RAs were effective at reducing the risk of endoscopic duodenal ulcers but not gastric ulcers. H2RAs usage was independent risk factors for severe small intestinal damage. Misoprostol significantly reduced the risk of endoscopic ulcers. Small studies showed that misoprostol prevented small intestinal injuries due to NSAIDs. A systematic review and metaanalysis showed that rebamipide acted better than placebo against short-term NSAIDs-induced gastroduodenal injury. Rebamipide was equal to or not superior to traditional strategies. Rebamipide showed beneficial effects against the small bowel damage when compared with placebo group.
Conclusions: In the countries where rebamipide is available, rebamipide is recommended as a first-line therapy. In the countries where rebamipide is not available, PPIs or misoprostol is recommended as a first-line therapy. If efficacy is given priority over adverse effects, PPIs are recommended as a first-line therapy. If fewer adverse effects are given priority over efficacy, misoprostol is recommended as a first-line therapy and PPIs as a second-line therapy.