NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity
- Mark Feldman, MD, MACP, AGAF, FACG
Mark Feldman, MD, MACP, AGAF, FACG
- Section Editor — Acid Peptic Disease
- Texas Health Presbyterian Hospital Dallas
- Clinical Professor of Internal Medicine
- University of Texas Southwestern Medical School at Dallas
- Shounak Das, MD
Shounak Das, MD
- Volunteer Clinical Faculty, University of Texas Southwestern Medical School at Dallas
- Department of Internal Medicine, Texas Health Presbyterian Hospital Dallas
Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, cause considerable morbidity and mortality related to gastric and duodenal ulcer disease . In rheumatoid arthritis patients alone, it has been estimated that gastrointestinal (GI) toxicity related to NSAID use accounts for at least 2600 deaths in the United States annually . Thus, prevention of NSAID-induced GI damage is an important clinical issue.
Misoprostol, proton pump inhibitors, and H2 receptor antagonists have been evaluated as prophylactic therapies for patients taking NSAIDs. In addition, the selective COX-2 inhibitors (coxibs) introduced a novel strategy for the prevention of NSAID-related gastroduodenal toxicity. However, the advantage of these coxibs over nonselective NSAIDs is debatable and 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".)
Multiple studies have evaluated factors for gastroduodenal toxicity from nonsteroidal anti-inflammatory drugs (NSAIDs) and assessment of these risk factors is recommended for identifying patients who should be considered for prophylaxis if it is felt that an NSAID must be given [3-5]. (See "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity".)
A prospective study of 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 ulcer: age >64, a history of prior adverse GI events, or concurrent use of low dose aspirin .
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- RISK FACTORS
- NONSELECTIVE NSAIDs
- ENTERIC-COATED AND BUFFERED ASPIRIN
- Low dose aspirin for cardiovascular protection
- Dual antiplatelet therapy (eg, aspirin and clopidogrel)
- ROLE OF HELICOBACTER PYLORI
- SELECTIVE COX-2 INHIBITORS
- Cardiovascular risks
- PREVENTION STRATEGIES
- Proton pump inhibitors
- - Lansoprazole versus misoprostol
- - Esomeprazole with nonselective NSAIDs or COX-2 inhibitors
- - Celecoxib with low dose aspirin
- - Etoricoxib versus a nonselective NSAID
- - Conventional NSAID with a PPI or misoprostol versus a COX-2 inhibitor
- H2 receptor antagonists
- COX-inhibiting nitric oxide donator NSAIDs
- Aspirin-phosphatidylcholine combination
- CONSENSUS STATEMENTS AND GUIDELINES
- MONITORING PATIENTS TAKING NSAIDS
- SUMMARY AND RECOMMENDATIONS