Effects of very low dose daily, long-term aspirin therapy on gastric, duodenal, and rectal prostaglandin levels and on mucosal injury in healthy humans

Background & Aims: The safety of low-dose daily aspirin therapy in the gast rointestinal tract is uncertain. Our objectives were to evaluate the long-t erm effects of very low daily aspirin doses in the gastrointestinal tract a nd effects on platelet-derived serum thromboxane levels in volunteers. Meth ods: Subjects were randomized to receive 10 mg (n = 8), 81 mg (n = 11), or 325 mg (n = 10) aspirin daily for 3 months. Before administration of aspiri n, all subjects underwent gastroduodenoscopy, and most underwent proctoscop y for assessment of mucosal injury and prostaglandin content. After 1.5 and 3 months, subjects again underwent gastroduodenoscopy and, at 3 months, an other proctoscopy. Results: Each aspirin dose (even 10 mg) significantly re duced gastric mucosal prostaglandin levels, to similar to 40% of the baseli ne value. All three doses also induced significant gastric injury, and 325 mg caused duodenal injury. Three subjects developed gastric ulcers, 1 while taking 10 mg/day of aspirin. Furthermore, aspirin at 81 mg/day and 325 mg( day (but not 10 mg/day) significantly reduced duodenal mucosal prostaglandi n levels to similar to 40% of the baseline value. Only 325 mg of aspirin pe r day significantly reduced rectal mucosal prostaglandin levels to similar to 60% of the baseline value. Serum thromboxane levels were inhibited 62%, 90%, and 98% with 10, 81, and 325 mg of aspirin. Conclusions: The findings explain aspirin's predominant gastric toxicity and question the safety of e ven 10 mg of aspirin daily.