2.4. Selective NSAID use and Gastrointestinal Risk

Like nonselective NSAIDs, celecoxib use may be associated with an increased risk of serious gastrointestinal (GI) adverse events, including potentially fatal GI bleeding, ulceration, or gastric/intestinal perforation. The risk of NSAID-associated severe GI adverse events increases in patients with a history of peptic ulcer disease, GI bleeding, smoking, alcohol use, concurrent use of anticoagulants or oral corticosteroids, advanced age, poor health and prolonged NSAID use. However, celecoxib may be associated with fewer GI adverse events due to selective COX-2 inhibition. Short-term trials (3 to 6 months) have shown celecoxib to be associated with significantly fewer GI complications compared to a nonselective NSAID plus a proton pump inhibitor (PPI) (e.g., diclofenac plus omeprazole) and a Cochrane review found significantly fewer ulcer complications with COX-2 inhibitors compared to nonselective NSAIDs. Chan and cohorts, in a randomized, double-blind trial, found that celecoxib administered concurrently with the PPI, esomeprazole, was significantly better in preventing ulcer bleeding in high risk patients compared to celecoxib monotherapy. In a case-control study, Patterson et al. observed that outpatients in the United States using commonly prescribed nonselective NSAIDs and COX-2 inhibitors from 1999 to 2003 were two times more likely to be hospitalized for peptic ulcer bleeding and perforation following nonselective NSAID use compared to those receiving celecoxib. Additionally, a recent small study suggests that lower GI bleeding may occur less frequently following COX-2 inhibitor use compared to that seen with nonselective NSAIDs. This study was criticized, though, as investigators used hemoglobin decrease rather than documented lower GI bleeds to assess outcomes. Further long-term studies are necessary to substantiate the perceived lower GI risk associated with COX-2 inhibitors.