Clinical potential of cyclo-oxygenase-2 inhibitors

On the basis of their reduced potential to cause injury to the gastroduodenal mucosa, cyclo-oxygenase (COX)-2-selective inhibitors were developed and marketed as a safer alternative to traditional nonsteroidal anti-inflammatory drugs (NSAIDs). This manuscript reviews the major steps leading to the introduction of COX-2-selective inhibitors into clinical practice, from the identification of the COX isoenzymes to their various roles in physiological and pathological processes. The available data show that COX-2 inhibitors have a favourable safety profile and are at least as effective as traditional NSAIDs for the treatment of pain and inflammatory conditions with a reduced incidence of gastrointestinal complications. Emerging evidence points to new and unanticipated effects from these agents. COX-2 inhibition appears to play an important role in the modulation of intestinal polyposis and colorectal carcinogenesis. Additionally, COX-2 expression may be associated with inflammatory responses leading to the occurrence of Alzheimer's disease and potentially, COX-2 inhibitors could be used to retard the progression of this condition. However, by decreasing prostacyclin production, COX-2 inhibitors may lead to increased prothrombotic activity and increase the risk of cardiovascular events. Until further large-scale prospective studies are performed, and the magnitude of these potential risks is quantified, COX-2 inhibitors should be used with caution in patients at risk for cardiovascular morbidity.