Preventing NSAID Toxicity to the Upper Gastrointestinal Tract

Prevention of gastrointestinal toxicity begins with the selection of an appropriate analgesic or anti-inflammatory agent. For conditions without inflammation, such as some cases of osteoarthritis, an analgesic with no risk for gastrointestinal toxicity is appropriate. Risk factors for nonsteroidal anti-inflammatory drug (NSAID)-related complications include advanced age; history of ulcer disease or gastrointestinal bleeding; concomitant corticosteroid or anticoagulant use; use of high-dose or multiple NSAIDs; and certain chronic diseases, such as cardiovascular disease. If an NSAID must be used in a patient with risk factors, the patient should receive the lowest-risk NSAID and, in most cases, co-therapy to reduce the risk for NSAID-associated ulcers and their complications. The PGE1 prostaglandin analogue misoprostol is highly efficacious for the prevention of both gastric and duodenal ulcers and has also been shown to reduce the incidence of NSAID-induced ulcer complications. Side effects, such as diarrhea, may limit patient acceptance of the drug. Acid suppression with traditional ulcer-healing doses of H2-blockers significantly reduces rates of duodenal ulcer but is ineffective in reducing gastric ulceration. More potent acid inhibition with double-dose H2-blockers reduces rates of both gastric and duodenal ulcers. Proton-pump inhibitors, such as omeprazole, have been shown to prevent gastric and duodenal ulcers with an efficacy equal to that of misoprostol. They also reduce NSAID-related dyspepsia. Specific cyclooxygenase-2 (COX-2) inhibitors are associated with a markedly reduced rate of endoscopic ulcers. Very high-risk patients who receive these agents may still require co-therapy to prevent complications or reduce dyspepsia. This protocol may be changed by the results of long-term gastrointestinal outcome studies now underway.