An update on nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors

Selective inhibitors of the cyclooxygenase-2 enzyme were developed to treat pain and inflammation while reducing the risk of the serious gastrointestinal side effects seen with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). The results of several clinical trials have demonstrated an apparent increased risk of serious cardiovascular events in patients taking the COX-2-selective inhibitors. Although the risk was observed originally with trials conducted with rofecoxib, it was attributed generally to the entire class of COX-2-selective drugs based on a similar mechanism of action and a hypothesis that predicted the possibility of a prothrombotic effect of the drugs compared with nonselective NSAIDs. Subsequent studies have demonstrated that elevated cardiovascular risk is not limited to the use of COX-2-specific inhibitors. An increase in cardiovascular risk actually has been seen with anti-inflammatory drugs of the NSAID class, regardless of whether they are selective or nonselective inhibitors. The US Food and Drug Administration has recommended that all such drugs carry a black box warning for gastrointestinal and cardiovascular risks.