Rationalizing Cyclooxygenase Inhibition for Optimization of Efficacy and Safety Profiles
Current status of nonsteroidal anti-inflammatory drug (NSAID) use in the United States: risk factors and frequency of complications

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Abstract

Gastrointestinal (GI) toxicity is a major limiting factor in the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Because of the widespread use of these medications, the morbidity and costs associated with GI complications of NSAID use are significant. On the other hand, the costs of providing prophylactic cotherapy to all patients to prevent NSAID-induced ulcers and bleeding are prohibitive. The presence of specific risk factors (advanced age, prior peptic ulcer disease and bleeding, high NSAID doses and concomitant therapy with corticosteroids or anticoagulants) identifies patients who are most likely to have a GI complication. The recognition of these risks in specific patients may influence therapeutic decisions that could decrease the morbidity and costs of NSAID therapy.

Section snippets

Mucosal lesions

Numerous prospective studies have identified a prevalence of 15–20% for gastric ulcers and 5–8% for duodenal ulcers after 12 weeks of therapy.6, 10, 11, 12, 13, 14 The development of ulcers cannot be predicted by the presence of abdominal pain, as the majority of ulcers are asymptomatic. It is only in a minority of cases that these ulcers cause life-threatening complications, including bleeding and perforation of the stomach or intestines.10 The vast majority of endoscopic lesions do not result

Prevention of NSAID-induced ulcers

The optimal means of avoiding NSAID-induced ulcer complications is to avoid using the medications whenever possible. Alternative analgesics and anti-inflammatory agents should always be considered. A recent prospective study, however, demonstrated a high rate of inappropriate NSAID use.21 In a setting where NSAID therapy is required, the risk of ulceration and presumably complications can be reduced with cotherapy with either a prostaglandin analogue or acid antisecretory therapy.22, 23, 24, 25

Risks factors for a gastrointestinal complication

As noted above, multiple case-control population and database studies have confirmed that NSAID use increases the risk of a significant GI complication (e.g., bleeding, hospitalization, surgery) from 3.9-fold to 7.8-fold, depending upon the study.7, 32, 33, 34, 35 A meta-analysis of 16 studies by Gabriel et al17 determined the overall odds ratio to be 2.74, although the studies evaluated were quite heterogeneous.

Summary

In summary, prior peptic ulcer disease (particularly if complicated), advanced age, high NSAID doses or multiple NSAIDs, and concomitant therapy with either corticosteroids or anticoagulants all increase the risk of a GI complication for patients taking NSAIDs chronically. There are some data to support comorbid illnesses, such as heart disease and rheumatoid arthritis, as well as heavy alcohol use, as factors that may also increase the risk of an NSAID-induced complication. Smoking and female

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