Risk factors associated with the development of gastroduodenal ulcers due to the use of NSAIDs

The risk of gastrointestinal mucosal injury with non-steroidal anti-inflammatory drugs (NSAIDs) is dose-dependent. Epidemiological studies have clearly demonstrated a rank order of risk of ulcer complications for commonly used NSAIDs, with ibuprofen consistently associated with the lowest risk and piroxicam with the highest. Antacids, H2 receptor antagonists and misoprostol all have drawbacks as prophylaxis. Of the cyclo-oxygenase (COX)-2 selective NSAIDs, rofecoxib is associated with a lower risk of gastrointestinal toxicity but there is uncertainty about the long-term risk associated with celecoxib. Rofecoxib has been associated with a significantly higher incidence of myocardial infarction than naproxen that may counteract the benefit of greater gastrointestinal safety. At over-the-counter doses, the short duration of use and the low dose reduce the risk of a serious adverse event compared with chronic use at prescribed doses. Intermittent therapy with low-dose NSAIDs has proved extremely safe and it has not been determined whether COX-2 selective agents offer a safety advantage compared with such treatment.