Unmet needs in non-steroidal anti-inflammatory drug-induced upper gastrointestinal diseases

The use of traditional and cyclooxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs (NSAID) for the relief of pain and inflammation increases the risk of gastrointestinal side-effects ranging from dyspepsia to symptomatic and complicated ulcers. The COX-2-selective agents were designed to provide comparable pain relief to traditional NSAID, with a reduced rate of adverse gastrointestinal events. However, there appears to be little clinically significant difference between COX-2 and traditional NSAID in terms of dyspepsia, a common cause of the discontinuation of a traditional NSAID. Furthermore, concomitant aspirin use substantially reduces the gastrointestinal safety advantage of COX-2-selective drugs. An increase in the numbers of people taking low-dose aspirin for cardioprotection, an aging population and potential chemoprevention benefits are resulting in the rising consumption of NSAID. Proton pump inhibitors have a demonstrated role in the treatment and prevention of both non-selective NSAID and selective COX-2 inhibitor-related upper gastrointestinal damage. However, the use of gastroprotective agents is far from optimal, and many high-risk patients are not being clearly identified. At the same time, inappropriate low-dose aspirin use is placing low cardiovascular risk patients at risk of gastrointestinal bleeding. Combined with the recent withdrawal of rofecoxib and valdecoxib from the market because of excess cardiovascular adverse events, and concerns about the safety of other COX-2 inhibitors, a review of strategies to reduce the overall risks in users of anti-inflammatory drugs is timely. This article examines the current issues of understanding and managing NSAID-induced upper gastrointestinal diseases.