Aspirin has been a commercial drug for over a century, although for most of this history, an understanding of its mechanism
of action, as an inhibitor of cyclooxygenase (COX) activity and thus of prostanoid synthesis, was lacking. Over the past fifty
years, a large number of other nonsteroidal antiinflammatory drugs (NSAIDs) have been developed, and a much deeper understanding
of inflammation and prostanoid action has emerged. Indeed, a new class of selective inhibitors of the cyclooxygenase-2 isozyme
was introduced, about ten years ago, and these so-called coxibs quickly became regarded as preferable, in certain clinical
contexts, to avoid side effects associated with the use of aspirin and previously developed NSAIDs. This regard for coxibs
has been challenged, sometimes infamously, as cardiovascular events associated with coxib use have become apparent. A variety
of clinical trials have led to seemingly conflicting data concerning the roles of COX-1 and COX-2, and the implications of
their relative inhibition, in cardiovascular health and disease. In this Review, the authors offer an assessment of drug pharmacokinetics
and enzyme physiology that reconciles cardiovascular appraisals from a wide array of clinical data.
