Cyclooxygenase-2 inhibitors and cardiovascular risk

Cyclooxygenase-2 inhibitors, or coxibs, designed to provide comparable pain relief to traditional nonsteroidal anti-inflammatory drugs with reduced risk of gastrointestinal complications, have come under substantial recent scrutiny because of an increased likelihood of adverse cardiovascular events associated with their use.

Data concerning the cardiovascular risk associated with coxibs comes from three main sources: basic research demonstrating the potential for inhibitors of the cyclooxygenase-2 enzyme to promote a prothrombotic state; observational data suggesting an increased risk associated with the use of certain cyclooxygenase-2 inhibitors, and randomized trial data suggesting an increased risk associated with a variety of cyclooxygenase-2 inhibitors compared with either a traditional nonsteroidal anti-inflammatory drug, or placebo.

An increased risk of adverse cardiovascular events has been demonstrated with multiple cyclooxygenase-2 inhibitors, and this increased risk has led to the withdrawal from the market of all but one of these agents in the US. While several questions regarding the safety of coxibs remain, especially the role of dose in the increased risk and whether increased cardiovascular risk extends to traditional nonsteroidal anti-inflammatory drugs as well, clinicians should be cautioned about an increased possibility of adverse cardiovascular events in patients requiring therapy with coxibs.