Reducing clinically significant gastrointestinal toxicity associated with nonsteroidal antiinflammatory drugs

To evaluate the efficacy of treatment strategies to reduce clinically significant gastrointestinal adverse effects associated with nonsteroidal antiinflammatory drugs (NSAIDs).

A MEDLINE search (1966-November 2003) was performed to identify relevant articles. Key search terms included proton-pump inhibitors, histamine H2 antagonists, misoprostol, cyclooxygenase-2 (COX-2) selective inhibitors, nonsteroidal antiinflammatory agents, stomach ulcer, prevention, and economics. Additional references were obtained from cross-referencing the bibliographies of selected articles.

All information obtained from the MEDLINE search was reviewed. To provide the most clinically relevant information, only randomized controlled trials are included in this review.

Clinically significant upper gastrointestinal adverse events, such as ulcers and ulcer complications, associated with NSAIDs are a cause of significant morbidity and mortality in the US. Interest in strategies to reduce the risk of these adverse events is high among clinicians and patients. Misoprostol, high-dose H2-receptor antagonists, proton-pump inhibitors, and COX-2 inhibitors have been shown to reduce this risk. Misoprostol and proton-pump inhibitors are more effective than H2-receptor antagonists; dose-related diarrhea limits the clinical utility of misoprostol. These strategies may not provide enough protection in patients taking concomitant low-dose aspirin therapy or patients with a history of ulcer complications.

COX-2 inhibitors and proton-pump inhibitors are effective and well-tolerated therapies to reduce clinically significant upper gastrointestinal adverse events associated with NSAIDs.