Endoscopic comparison of cimetidine and sucralfate for prevention of naproxen-induced acute gastroduodenal injury

Abstract

Nonsteroidal antiinflammatory drug-induced gastroduodenal mucosal damage observed endoscopically is usually categorized as hemorrhages, erosions, or ulcerations. We undertook this study to determine whether the injury produced by a commonly prescribed NSAID, naproxen, could be reduced by cotherapy with sucralfate or cimetidine and to determine how dependent the differences in the degree of protection against mucosal injury measured were on the scoring system used. Four groups of 20 healthy volunteers with endoscopically normal gastric and duodenal mucosa received naproxen (500 mg twice a day) plus cimetidine (300 mg four times a day or 400 mg twice a day), sucralfate (1 g four times a day), or placebo for seven days. After seven days of therapy, a second endoscopy was performed. Separate scoring systems were used for the presence of hemorrhages, erosions, and a combination of both types of injury. There were significantly fewer mucosal hemorrhages present when naproxen and cimetidine were administered than when naproxen was administered with placebo or sucralfate (placebo vs 300 mg cimetidine, P=0.04, and placebo vs 400 mg cimetidine, P=0.006, placebo vs sucralfate, P=0.26). Both cimetidine dosages resulted in significantly fewer hemorrhages than were present following cotherapy of naproxen and sucralfate (P<0.05). In contrast, there was no discernible difference in the mucosal injury between placebo and any drug or between any two active therapies when the injury was evaluated based on the presence of gastric erosions. Duodenal damage was infrequent and slight following naproxen administration; erosions were present in all drug treatment groups but were numerous in only 10% (two of 20) of naproxen-placebotreated subjects, and there was no significant difference between any two groups. The scoring system that used the combination of hemorrhages and erosions showed that the naproxen-placebo group had significantly more duodenal injury than either 400-mg cimetidine or sucralfate group (P<0.02, for each). We conclude that the coadministration of either H₂-receptor antagonists or sucralfate fails to produce any clinically meaningful reduction in naproxen-induced acute gastroduodenal mucosal erosion or ulceration and that reliance on reductions in endoscopic damages scores either based on, or heavily influenced by, hemorrhages (or hemorrhages plus erythema) may provide misleading information to the clinician.