The associations between nonsteroidal anti-inflammatory drugs (
NSAIDs) and the presence and complications of gastroduodenal erosions and
ulcers are well established. Evidence that
acid aggravates
NSAID-induced injury provides a rationale for minimising such damage by
acid suppression. Other strategies discussed include avoidance of
NSAIDs or minimising their dosage, selecting
NSAIDs known to cause less damage, and co-prescription of various agents. Cytoprotection with
misoprostol, a
prostaglandin analogue, has been shown to be effective in reducing
NSAID-related
peptic ulcers and their complications. Unfortunately, adverse effects may limit compliance in some patients.
Histamine H2 antagonists have only limited efficacy in the prevention of
NSAID-induced
ulcers in humans, particularly in the stomach, except at higher than standard dosages. This may relate to their relatively modest effect in elevating gastric pH, especially in comparison with
proton pump inhibitors. Several studies now confirm the efficacy of
proton pump inhibitors in the short and longer term prevention of
NSAID-induced upper gastrointestinal injury. Placebo-controlled studies suggest reductions of over 70% in gastric and
duodenal ulcer rates over 3 to 6 months. The recent ASTRONAUT (
Acid Suppression Trial:
Ranitidine versus
Omeprazole for
NSAID-Associated
Ulcer Treatment) study documented the greater prophylactic efficacy of
omeprazole over
ranitidine at standard dosages for 6 months. The OMNIUM (
Omeprazole versus
Misoprostol for
NSAID-Induced
Ulcer Management) study showed
omeprazole to be slightly more effective overall than
misoprostol in preventing the upper gastrointestinal adverse effects of
NSAIDs, with both substantially more effective than placebo, although
misoprostol was somewhat less well tolerated. Although substantial reductions in
NSAID ulceration are now achievable when co-
therapy with a
proton pump inhibitor is given, a few patients will still develop
ulcers and their complications. Hence the judicious use of
NSAIDs in the first instance cannot be overemphasised.