Numerous studies using varying methodologies and outcome measures have examined the gastrointestinal risks of
aspirin and nonaspirin nonsteroidal antiinflammatory
drug (
NSAID) use. Despite the large volume of literature, clarity regarding the key risk factors and their quantitative importance is lacking. We performed a comprehensive review of the literature to summarize the incidence of gastrointestinal injury in populations with varying risk characteristics using agents that inhibit both
isoforms of
cyclooxygenase and those that selectively inhibit only
cyclooxygenase-2 (COX-2).Although risk estimates vary, the risk of serious gastrointestinal complications in
NSAID users is approximately 2.5 to 4.5 times that of nonusers. The risk of
NSAID-related gastrointestinal
bleeding is augmented by concomitant low-dose
aspirin and could approach double the risk of
NSAID use alone. The preponderance of evidence shows that the risk of
NSAID-related gastrointestinal
bleeding is reduced approximately 50% with a
coxib as compared with traditional
NSAID. The relative risk of hospitalization resulting from upper gastrointestinal
bleeding for patients treated with a nonselective
NSAID was 4.4 (95% confidence interval [CI], 2.3-8.5) and 1.9 (95% CI, 1.0-3.5) when compared with
celecoxib and
rofecoxib, respectively.
Aspirin increases the risk of
NSAID-related gastrointestinal
bleeding in patients taking COX-2 selective inhibitors, with odds ratios ranging from 5.8 to 7.7; however, it is unknown whether this risk is greater than the risk from
aspirin alone. The risks from both traditional
NSAIDs and
COX-2 inhibitors are increased in the elderly, patients on anticoagulation, and patients with prior gastrointestinal events.Gastroprotective agents have been found to significantly reduce the risk for gastrointestinal injury in patients receiving
NSAID therapy, especially those receiving concurrent low-dose cardioprotective doses of
aspirin.
Proton pump inhibitors (PPIs) and
misoprostol both reduce the incidence of gastric and
duodenal ulcers, as well as recurrence of
ulcer complications in patients receiving
NSAIDs. The relative risk for
gastric ulcers ranged from 0.17 to 0.38, whereas for
duodenal ulcers, the range was 0.11 to 0.28. Although
misoprostol is slightly more effective in preventing
gastric ulcers in these patients, PPIs are better tolerated. Although
NSAIDs appear safe in "low-risk" populations, our review suggests that the use of gastroprotective cotherapy should be considered in patients at higher risk of
NSAID-related upper gastrointestinal
bleeding.