A randomized, placebo‐controlled study of the effects of naproxen, aspirin, celecoxib or clopidogrel on gastroduodenal mucosal healing

BACKGROUND: Many individuals with gastroduodenal ulcers require on-going, non-steroidal anti-inflammatory drug (NSAID) or anti-platelet therapy. AIMS: To evaluate the effects of these agents on gastroduodenal mucosal healing. METHODS: Helicobacter pylori-negative volunteers were randomized to receive naproxen, celecoxib, aspirin, clopidogrel or placebo. Antral and duodenal lesions were created endoscopically with a biopsy forceps. After 7 days of medication dosing, each lesion was scored [from 0 (low) to 8 (high)] using a validated methodology. The primary endpoint was the mean injury score. The secondary endpoint was the percentage of subjects with > or = 1 unhealed lesion. RESULTS: In all, 108 subjects completed the study. Naproxen impaired antral lesion healing more than placebo, clopidogrel, aspirin or celecoxib (mean injury score of 4.3 vs. 3.0, 2.7, 3.2, and 3.2, respectively, P < 0.05). Naproxen impaired duodenal lesion healing more than placebo, clopidogrel or aspirin (mean injury score of 4.0 vs. 2.4, 2.6, and 2.2, respectively, P < 0.05). More subjects taking naproxen than placebo or clopidogrel had > or =1 unhealed antral lesions (72.2% vs. 36.0% and 32.0%, respectively, P < 0.05) and unhealed duodenal lesions (61.1% vs. 16.0% and 28.0%, respectively, P < 0.05). CONCLUSIONS: Naproxen may impair gastroduodenal healing more than aspirin or celecoxib in H. pylori negative subjects. Clopidogrel did not impair mucosal healing.