Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial

BACKGROUND & AIMS: We assessed the risk of ulcers with low-dose aspirin and the interaction of low-dose aspirin with a COX-2 selective inhibitor in a double-blind trial that compared placebo, low-dose aspirin, rofecoxib + low-dose aspirin, and ibuprofen. METHODS: Osteoarthritis patients > or =50 years of age without ulcers or erosive esophagitis at baseline endoscopy were assigned randomly to placebo, enteric-coated aspirin 81 mg/day, rofecoxib 25 mg combined with aspirin 81 mg/day, or ibuprofen 800 mg 3 times a day. Repeat endoscopies were performed at 6 and 12 weeks. RESULTS: The 12-week cumulative incidence of ulcers was placebo (N = 381) 5.8%, aspirin (N = 387) 7.3%, rofecoxib combined with aspirin (N = 377) 16.1%, and ibuprofen (N = 374) 17.1% (P < 0.001 for rofecoxib combined with aspirin and for ibuprofen vs. each of placebo and aspirin). Over 12 weeks, mean increases in the number of erosions were placebo 0.17, aspirin 0.85 (P = 0.002 vs. placebo), rofecoxib combined with aspirin 1.67, and ibuprofen 1.91 (both P < 0.001 vs. aspirin and placebo). CONCLUSIONS: Low-dose aspirin alone did not significantly increase ulcer incidence. Addition of a cyclooxygenase-2 (COX-2) selective inhibitor to low-dose aspirin increased ulcer incidence, to a rate not significantly less than a nonselective nonsteroidal anti-inflammatory drug (NSAID) alone. Determining the relative impact of COX-2 selective inhibitors and nonselective NSAIDs on gastrointestinal mucosal injury in low-dose aspirin users will require further study.