Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial.
OBJECTIVE
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.
University of Southern California School of Medicine, Department of Medicine, Los Angeles 90033, USA. llaine@usc.edu
Loren
L
Laine
Eric S
ES
Maller
Chang
C
Yu
Hui
H
Quan
Thomas
T
Simon
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases; D012307:Risk Factors; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000453:epidemiology; D013450:Sulfones; D013608:Tablets, Enteric-Coated
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; D013608:Tablets, Enteric-Coated; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007052:Ibuprofen