1. Home>
2. Specialties>
3. General Medicine>
4. Summary and Comment

GI Complications with COX-2 Inhibitors

Two studies add to the growing body of evidence that risk is increased with these drugs.

With one selective cyclooxygenase (COX)-2 inhibitor — celecoxib — still available in the U.S. and another — etoricoxib — under review (Journal Watch Feb 21 2007), the gastrointestinal side-effect profile of these drugs remains of interest.

In a nested case-control study, researchers used a population-based U.K. database to compare 1561 patients with upper gastrointestinal complications (nonvariceal bleeding or perforation) and 10,000 age- and sex-matched controls. After adjustment for potentially confounding variables, the relative risk for upper GI complications was significantly elevated among current users of both traditional nonsteroidal anti-inflammatory drugs (RR, 3.7) and COX-2 inhibitors (RR, 2.6). Concurrent aspirin use eliminated the modest advantage of COX-2 inhibitors over traditional NSAIDs. Although information on individual drugs was limited by small numbers, etoricoxib was associated with a higher risk for upper GI complications than many traditional NSAIDs.

Another report analyzed upper GI complications in the previously published APPROVe trial (one of the trials showing increased cardiovascular risk with rofecoxib). In this polyp-prevention trial, 2587 volunteers received rofecoxib (25 mg daily) or placebo for 3 years. The incidence of upper GI events (symptomatic ulcer, perforation, obstruction, or bleeding) was significantly higher among rofecoxib recipients than placebo recipients (about 0.9% vs. 0.2% per year).

Comment: The first of these studies suggests that selective COX-2 inhibitors confer an increased risk for upper GI complications, although the risk appears somewhat less than that associated with traditional NSAIDs. The second study — a placebo-controlled trial — confirms the elevated risk with COX-2 inhibitors. This growing body of evidence indicates that clinicians who prescribe COX-2 inhibitors should not expect a completely benign upper GI safety profile.

— Allan S. Brett, MD

Published in Journal Watch General Medicine March 15, 2007

Citation(s):

García Rodríguez LA and Barreales Tolosa L. Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology 2007 Feb; 132:498-506.

• Medline abstract (Free)

Lanas A et al. Peptic ulcer and bleeding events associated with rofecoxib in a 3-year colorectal adenoma chemoprevention trial. Gastroenterology 2007 Feb; 132:490-7.

• Medline abstract (Free)

2011 Year in Review