In a very short time, COX-2 enzyme inhibitors have gone from the darlings to the 
pariahs of the pharmaceutical industry. These drugs were developed based on the 
hypothesis whereby selective inhibition of the COX enzyme would lead to 
reduction in pain and inflammation without associated gastrointestinal and 
bleeding risks. However, in September 2004, rofecoxib was voluntarily removed 
from the market for increased cardiovascular risk and in April 2005, valdecoxib 
was also withdrawn, at least in part, due to excess cardiovascular risk. 
Celecoxib was the first COX-2 inhibitor introduced and the only remaining one on 
the US market. There is consequently a justified concern that cardiovascular 
toxicity is a class effect of all COX-2 inhibitors. This article systematically 
reviews the evidence surrounding COX-2 inhibitors and cardiovascular risk. 
Although the evidence suggests a fairly consistent cardiovascular risk with 
rofecoxib, the evidence for cardiovascular risk with celecoxib is more 
equivocal. Although isolated studies have suggested some cardiovascular risk for 
celecoxib, the totality of the evidence suggests that any risk is likely to be 
small and comparable to traditional NSAIDs. The cardiovascular risks of COX-2 
inhibitors appear heterogeneous, influenced not only by the drug class, but also 
individual drug, dosage and patient characteristics. Specific modifying factors 
of the cardiovascular risk of COX-2 inhibitors including dose, concomitant 
drugs, individual cardiac and genetic risk profiles, will require further study.