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Upper GI Complications with Coxibs or Nonselective NSAIDs

In a subgroup of patients who did not take aspirin, coxibs were associated with significantly lower risk for UGI complications than were nonselective NSAIDs.

Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with three- to fivefold increased risk for upper gastrointestinal (UGI) complications. Randomized trials have suggested that cyclooxygenase-2 inhibitors (coxibs) might impart significantly lower risk than nonselective NSAIDs. Few data are available to compare the complication rates of these two classes of drugs in the general population.

To address this issue, investigators in the U.K. performed an industry-sponsored nested case-control study. They identified 1561 cases of UGI complications that occurred from 2000 to 2005 and that were recorded in The Health Improvement Network database. Cases were matched for age, sex, and calendar year to 10,000 randomly selected controls. Use of nonselective NSAIDs or coxibs was determined retrospectively in both groups.

Among all patients, nonselective NSAIDs imparted higher risk for UGI complications than did no use (odds ratio, 3.7; 95% CI, 3.1–4.3); coxibs also imparted greater risk than did no use (OR, 2.6; 95% CI, 1.9–3.6). In a direct comparison, patients who took coxibs were somewhat less likely to have UGI complications than were patients who took nonselective NSAIDs (OR, 0.8; 95% CI, 0.6–1.1), but this difference was not statistically significant. In the subgroup of patients who did not take aspirin, the difference between nonselective NSAIDs and coxibs was greater and was statistically significant (OR, 0.6; 95% CI, 0.4–0.9). Coxibs, compared with nonselective NSAIDs, did not benefit patients who also took aspirin (OR, 1.9; 95% CI, 1.0–3.6).

In further subgroup analyses, higher doses of both nonselective NSAIDs and coxibs increased risk for complications. Nonselective NSAIDs with longer durations of action (serum half-life) or delayed-release formulations were associated with higher risks for complications. The investigators concluded that coxibs had a better safety profile for UGI complications than did nonselective NSAIDs but that this effect was negated by concomitant use of aspirin.

Comment: The interpretation of these results must be tempered somewhat by the retrospective data collection and reliance on prescription information for presumed exposure. However, prior studies using the same methodology have suggested that the data are robust. The finding that coxibs are associated with higher risk for UGI complications than is placebo, but with less risk than that of nonselective NSAIDs, is consistent with other studies, including one published in the same issue of Gastroenterology (Journal Watch Gastroenterology May 11 2007). The magnitude of the difference between coxibs and nonselective NSAIDs might be even greater than that reported here if patients at higher risk for complications were more likely to receive coxibs. That concomitant use of aspirin negates the benefit of coxibs is not surprising, as aspirin irreversibly inactivates both COX-1 and COX-2, rendering the selective effects of coxibs moot until new enzymes are produced.

— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

Published in Journal Watch Gastroenterology May 11, 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)