Review

Aspirin has been a commercial drug for over a century, although for most of this history, an under-standing 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 inflam-mation and prostanoid action has emerged. Indeed, a new class of selective inhibitors of the cyclooxy-genase-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 traditional NSAIDs. This regard for coxibs has been challenged by the unraveling of a previously unknown cardiotoxicity associated with COX-2 inhibition. Here, we discuss the mechanisms underly-ing the cardiovascular effects of low-dose aspirin, traditional NSAIDs, and coxibs, and we attempt to reconcile the human pharmacology of COX isozyme inhibition with the contrasting cardiovascular phe-notypes that have emerged from randomized clinical trials