COX-2 inhibitor no safer than naproxen and PPI.

* Clinical Question

In patients with previous peptic ulcer, is celecoxib (Celebrex) safer than naproxen taken with an proton pump inhibitor?

* Bottom Line

In patients at high risk for recurrent peptic ulcer with nonsteroidal anti-inflammatory drug (NSAID) therapy, celecoxib was no more effective than the combination of naproxen (Naprosyn) and lansoprazole (Prevacid) in preventing serious adverse effects and was more likely to cause dyspepsia symptoms. The benefit of cyclo-oxygenase-2 (COX-2) inhibitors in preventing serious gastrointestinal adverse events is likely overstated. (LOE=1b-)

Study Design

Randomized controlled trial (nonblinded)

Funding

Self-funded or unfunded

Allocation

Uncertain

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

The researchers conducting this study in Hong Kong identified adults who developed upper gastrointestinal bleeding while receiving NSAIDs. Approximately half (56%) of the patients were positive for Helicobacter pylori. Following 6-week treatment of the ulcer, the 242 patients were randomly assigned (allocation concealment uncertain) to receive 6 months of treatment with either celecoxib 200 mg daily or naproxen 250 mg 3 times daily with lansoprazole 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-percentage-point difference in ulcer relapse, assuming a 4.5% 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/dL, perforation, or obstruction. This outcome occurred in 11 patients (4.5%)--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, though other adverse events were similar between the 2 groups.

A similar study found no difference in adverse events comparing celecoxib with diclofenac plus omeprazole (Gastroenterology 2004; 127:1038-1043). The proton pump inhibitor therapy may not be necessary; one other study has shown that celecoxib is not better than either ibuprofen or diclofenac without acid suppression in preventing serious gastrointestinal side effects in patients (JAMA 2000; 285:1247-1255).

FAST TRACK

Celecoxib was no more effective in preventing adverse effects from peptic ulcer than naproxen and lansoprazole

Lai KC, Chu KM, Hut WM, et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. Am J Med 2005; 118:1271-1278.