Risk of Upper Gastrointestinal Bleeding and Perforation Differs Among NSAIDs

DynaMed Weekly Update - Volume 5, Issue 27

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been known to increase the risk of upper gastrointestinal (GI) bleeding. Newer COX-2 inhibitors were introduced with the promise of reduced GI adverse effects.

A recent systematic review with data from 9 cohort and case-control studies with over 50,000 patients has rank-ordered the risks of upper GI bleeding and perforation associated with use of a number of different NSAIDs. The lowest risks were found for the COX-2 inhibitor celecoxib (Celebrex) (relative risk [RR] 1.42, 95% CI 0.85-2.4) and for the traditional NSAIDS ibuprofen (Motrin and others) (RR 2.69, 95% CI 2.2-3.3) and aceclofenac (RR 1.44, 95% CI 0.65-3.2). Aceclofenac is not available in the United States. The highest risks were associated with piroxicam (Feldene) (RR 9.94, 95% CI 6-16.5) and ketorolac (Toradol) (RR 14.54, 95% CI 5.9-36). Diclofenac (Voltaren), meloxicam (Mobic), indomethacin (Indocin), naproxen (Aleve), and ketoprofen (Oruvail) were all associated with intermediate risk.

For traditional NSAIDS as a class, risk varied with duration of use. The risk was highest within the first 30 days of use (RR 5.22, 95% CI 3.8-7.2) and lower, but still significantly increased, after more than a year of use (RR 2.9, 95% CI 2.2-3.8). The COX-2 inhibitor, rofecoxib (Vioxx), which was withdrawn from the market in 2004 for cardiovascular toxicity, was also reviewed and was classified as having lower relative risk than traditional NSAIDs (Arthritis Rheum 2010 Jun;62(6):1592).

For more information, see the Acute upper gastrointestinal bleeding and Prevention of NSAID-induced gastrointestinal toxicity topics in DynaMed.


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