Cardiovascular risks of cyclooxygenase inhibition

Millions of patients use nonsteroidal antiinflammatory drugs (NSAIDs) for relief of arthritic pain. Although NSAIDs reduce pain, their use has been linked to gastroduodenal complications. Selective inhibition of the cyclooxygenase (COX)-2 enzyme appeared to offer patients similar pain relief with an improved adverse-effect profile. However, accumulating experiences have raised concerns regarding the cardiovascular toxicities of the selective COX-2 inhibitors. Although selective COX inhibitors provide more gastrointestinal protection than NSAIDs, the unbalanced inhibition of prostaglandins may promote cardiovascular complications. Variability in study designs and inconsistency in results have made the evaluation of NSAID and COX-2 inhibitor safety very difficult, creating confusion among health care practitioners. We examine the pharmacologic and clinical evidence that defines the cardiovascular risk associated with COX inhibition.