Gastroenterology 2001: Diagnostics & TherapeuticsApproaches to nonsteroidal anti-inflammatory drug use in the high-risk patient☆,☆☆
Section snippets
Endoscopic signs of injury
A single dose of aspirin leads to gross gastric injury in the form of subepithelial hemorrhages within 15–30 minutes of ingestion.5, 6, 7 Continued aspirin ingestion for 24 hours (650 mg 4 times a day) leads to the development of gastric erosions.5, 8 Virtually all subjects given aspirin develop these lesions in the first days of use.5, 8 However, subepithelial hemorrhages and erosions are mucosal lesions, whereas blood vessels of significant size are located in the submucosa or deeper. Thus,
Risk of clinical events
Only a small proportion of NSAID users develop GI complications. However, given the exceptionally widespread use of NSAIDs and aspirin, this small proportion translates into a large absolute number of NSAID users developing clinical GI events. A variety of epidemiologic studies (cohort and case-control) show a significant increase in clinical upper GI events with NSAID use (aspirin and nonaspirin NSAIDs), with most reports suggesting a 2–6-fold increase over the incidence in people not taking
Risk factors for NSAID-associated GI events
A variety of clinical factors have been reported to significantly increase the risk of developing NSAID-associated GI events. Important factors that are validated in multiple studies include history of ulcer or GI complications, increasing age, concomitant anticoagulation therapy, concomitant corticosteroid use, and high-dose NSAID use.
Risks with individual NSAIDs
NSAIDs inhibit prostaglandin production by inhibiting COX. Two isoforms of the COX enzyme are known to be involved in prostaglandin synthesis. COX-1 is constitutively expressed and generates prostaglandins involved in GI mucosal protection and platelet function, whereas COX-2 is induced at sites of inflammation to generate prostaglandins that mediate inflammation and pain. The anti-inflammatory effects of nonselective NSAIDs appear to be mediated via COX-2 inhibition, whereas the harmful
Strategies to decrease NSAID-associated GI events
Several strategies may be used to decrease the risk of NSAID-associated GI events. First, GI complications can be avoided by the use of non-NSAID analgesics, when possible. Second, use of the lowest effective dose of an NSAID will decrease the chance of complications. Third, medical cotherapy can be used in patients with increased risk of complications. Finally, the development of less injurious NSAIDs such as the COX-2–specific inhibitors will decrease the risk of GI events.
Economic considerations
Economic considerations are key in determining management of the GI risk in patients taking NSAIDs. The cost of NSAID-associated GI side effects is substantial. For example, using the Quebec health insurance database for 1993–1997, Rahme et al.83 estimated that for each dollar spent on NSAIDs, $0.66 is spent on their GI side effects. Using Medicaid data from Washington, D.C., for 1981–1983, Bloom84 found that 31% of the total cost of care for “arthritis” patients was for management of GI
Summary and recommendations
Endoscopic ulcers are found in ~15%–30% of patients who take NSAIDs regularly, but clinical GI events are relatively infrequent. Prospective outcome studies indicate an annual incidence of complicated GI events (perforation, obstruction, major bleeding) in arthritis patients of ~1.5% and an annual rate of all clinical GI events (complicated events plus ulcers discovered on work-up for significant GI symptoms) of ~3%–4.5%. Population cohort studies suggest that the annual rate of excess GI
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Address correspondence to: Loren Laine, M.D., GI Division, Department of Medicine, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, California 90033. e-mail: [email protected]; fax: (323) 226-7573.
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Dr. Laine has been a consultant and received research support from various pharmaceutical companies whose medications are discussed in this article.