The mechanisms by which
aspirin(ASA) and non-steroidal anti-inflammatory drugs (
NSAIDs) cause gastrointestinal symptoms are poorly understood. They probably arise from several causes, including direct and indirect mucosal injury, exacerbation of underlying
peptic ulcer disease or non-
ulcer dyspepsia, exacerbation of Helicobacter pylori
gastritis, and possibly motility disorders. No single form of
therapy has been generally successful. Because, in most cases, symptoms abate fairly rapidly with continued treatment, there is little evidence that benefit associated with any symptom-directed
drug therapy is superior to placebo beyond 4 weeks. Exceptions may be the subsets of patients with pre-existing
ulcer disease or
heartburn, exacerbated by the
NSAID therapy, who usually benefit from
acid-suppressive
drug treatment. Different
NSAIDs vary in the frequency with which their use leads to gastrointestinal(GI) complications such as haemorrhage, perforation, obstruction, or the symptomatic
ulcers from which about 40% of the complications arise. Most
gastroduodenal ulcers heal over time, albeit more slowly, with conventional doses of any of the available
anti-ulcer drugs. Maintenance
therapy may be needed in many patients who continue
NSAID therapy.
Anti-ulcer drugs have not, thus far, been shown to be more effective than placebo in preventing
ulcer complications or their recurrence. The use of COX-2-selective inhibitors appears, in outcome studies, to reduce gastrointestinal
bleeding, including
bleeding from
ulcers, but it is not established that the
ulcers protected were caused by
NSAIDs, as distinct from
ulcers exacerbating or recurring from antecedent
peptic ulcer disease. To-date, perforation or obstruction have not been shown to be affected by selective
COX-2 inhibitor drugs. If the major problem giving rise to severe
NSAID complications is pre-existing
peptic ulcer disease, it may yet emerge that the most effective approach will be the use of
proton pump inhibitor drugs, for the duration of
NSAID therapy, in a small subset of high-risk patients. Most other low-risk patients may not need any special care. Co-morbid conditions have a major impact on outcome of
NSAID therapy. Morbidity or even death attributable solely to
NSAIDs is probably small in normal patients, and requires little in the way of prophylaxis.