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 ≥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 ≥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.