Clinical Question: In patients with previous peptic ulcer, is celecoxib (Celebrex) safer than naproxen (Naprosyn) taken with a proton pump inhibitor?

Setting: Inpatient (any location) with outpatient follow-up)

Study Design: Randomized controlled trial (nonblinded)

Allocation: Uncertain

Synopsis: The researchers, conducting this study in Hong Kong, identified adults who developed upper gastrointestinal bleeding while receiving nonsteroidal anti-inflammatory drugs. Approximately one half (56 percent) of the patients were positive for Helicobacter pylori. Following six weeks of treatment for the ulcer, the 242 patients were randomly assigned (allocation concealment uncertain) to receive six months of treatment with celecoxib 200 mg daily or naproxen 250 mg three times daily with lansoprazole (Prevacid) 30 mg daily. The investigators and the patients were aware of treatment assignment, although a team of gastroenterologists who were unaware of treatment assignment adjudicated all endpoints. Analysis was by intention to treat. The study had the power to demonstrate a 7 percent point difference in ulcer relapse, assuming a 4.5 percent incidence of ulcer relapse.

The major outcome was ulcer complications: bleeding with melena or hematemesis or a drop in hemoglobin of at least 2 g per dL (20 g per L), perforation, or obstruction. This outcome occurred in 11 patients (4.5 percent), and although more occurred in the naproxen/lansoprazole group (n = 7), the rates were not statistically different. Patients receiving celecoxib were more likely to report dyspepsia symptoms during treatment, although other adverse events were similar between the two groups. A similar study found no difference in adverse events when comparing celecoxib with diclofenac plus omeprazole (Chan FK, et al. Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology October 2004;127:1038–43). The proton pump inhibitor therapy may not be necessary; one other study has shown that celecoxib is not better than ibuprofen or diclofenac (Voltaren) without acid suppression in preventing serious gastrointestinal side effects in patients (Silverstein FE, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflamatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Safety Study. JAMA September 13, 2000;284:1247–55).

Bottom Line: In patients at high risk of recurrent peptic ulcer with nonsteroidal anti-inflammatory drug therapy, celecoxib was no more effective than the combination of naproxen and lansoprazole in preventing serious adverse effects and was more likely to cause dyspepsia symptoms. The benefit of cyclooxygenase-2 inhibitors in preventing serious gastrointestinal adverse events is likely overstated. (Level of Evidence: 1b)