Effects of very low dose daily, long-term aspirin therapy on gastric, duodenal, and rectal prostaglandin levels and on mucosal injury in healthy humans.
OBJECTIVE
The safety of low-dose daily aspirin therapy in the gastrointestinal tract is uncertain. Our objectives were to evaluate the long-term effects of very low daily aspirin doses in the gastrointestinal tract and effects on platelet-derived serum thromboxane levels in volunteers.


METHODS
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 aspirin, all subjects underwent gastroduodenoscopy, and most underwent proctoscopy for assessment of mucosal injury and prostaglandin content. After 1.5 and 3 months, subjects again underwent gastroduodenoscopy and, at 3 months, another proctoscopy.


RESULTS
Each aspirin dose (even 10 mg) significantly reduced gastric mucosal prostaglandin levels, to approximately 40% of the baseline 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 prostaglandin levels to approximately 40% of the baseline value. Only 325 mg of aspirin per day significantly reduced rectal mucosal prostaglandin levels to approximately 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 even 10 mg of aspirin daily.
Cryer
B
B
Medical Service, Dallas VA Medical Center, and Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA. bcryer@mednet.swmed.edu
Feldman
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D016145:Endoscopy, Digestive System; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000096:biosynthesis*; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D013929:Thromboxane B2; D001241:Aspirin