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NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity

Mark Feldman, MD, MACP, AGAF, FACG
Shounak Das, MD
Section Editor
J Thomas Lamont, MD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, cause considerable morbidity and mortality related to gastric and duodenal ulcer disease [1]. Thus, prevention of NSAID-induced GI damage is an important clinical issue.

Misoprostol, H2 receptor antagonists, and proton pump inhibitors have been evaluated as prophylactic therapies for patients taking NSAIDs. In addition, the selective COX-2 inhibitors (coxibs) introduced a novel strategy for the reduction of NSAID-related gastroduodenal toxicity. However, the advantage of these coxibs over nonselective NSAIDs is still debatable and concerns about cardiovascular toxicity has limited the use of coxibs. (See "Overview of selective COX-2 inhibitors" and "COX-2 selective inhibitors: Adverse cardiovascular effects".)

Strategies for the primary prevention of gastroduodenal toxicity due to NSAIDs will be reviewed here. Emphasis will be placed upon studies that used clinically relevant end points (symptomatic ulcers and complicated ulcers, including bleeding, perforating, and obstructing ulcers). Studies using endoscopic detection of ulcers as the end point will be cited only when data on more meaningful clinical end points are lacking. The pathogenesis, treatment, and secondary prevention of NSAID-induced gastroduodenal injury are discussed separately. (See "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity" and "NSAIDs (including aspirin): Treatment of gastroduodenal toxicity" and "NSAIDs (including aspirin): Secondary prevention of gastroduodenal toxicity".)


Studies have evaluated risk factors for gastroduodenal toxicity from nonsteroidal anti-inflammatory drugs (NSAIDs) and assessment of these factors is recommended for identifying patients who should be considered for primary prophylaxis if it is felt that an NSAID must be given [2-4]. (See "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity".)

One prospective study of 34,701 osteoarthritis and rheumatoid arthritis patients ages 50 and above randomized to either etoricoxib or diclofenac use found the following factors to be significant predictors for gastrointestinal (GI) toxicity including bleeding, perforation, obstruction, or uncomplicated ulcer: age >64, a history of prior adverse GI events, or concurrent use of low dose aspirin [5].

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Literature review current through: Nov 2017. | This topic last updated: Mar 09, 2017.
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