To the Editor: I am concerned that several statements in the article on cyclooxygenase-2 (COX-2) inhibition by Cleland and colleagues1 do not accurately reflect the clinical data.

The authors postulate a prothrombotic tendency of celecoxib on the basis of the CLASS study (comparing celecoxib with ibuprofen or diclofenac)2 and four case reports. The authors concede that celecoxib has no effect on the rate of myocardial infarction (MI) in the CLASS study (a conclusion also reached by the United States Food and Drug Administration [FDA] review of CLASS3), which would seem to contradict their hypothesis that celecoxib is prothrombotic.

Cleland and colleagues speculate that the differences between the CLASS study and the VIGOR study (which compared rofecoxib with naproxen)4 may be explained by low-dose aspirin use in CLASS and failure to use aspirin in 4% of patients in VIGOR with "CV [cardiovacular] risk factors". This speculation is unfounded. In the CLASS study patients in all treatment groups who used aspirin had higher MI rates than non-aspirin users, and presumably this higher rate would have been observed in VIGOR if aspirin users had been enrolled. This higher rate is probably because aspirin use serves as a marker for increased CV risk. In patients in CLASS similar to the 4% with "CV risk factors" in VIGOR, MI rates were similar in the celecoxib and non-steroidal anti-inflammatory drug (NSAID) groups (data on file, Pharmacia) and numerically much lower than in the VIGOR study subgroup.

On the basis of these two flawed arguments, Cleland and colleagues apparently extrapolate the high rate of MI seen with the use of rofecoxib to celecoxib and suggest that high MI rates are a "class" effect. This proposal is scientifically unsound and is not supported by other clinical data, including over 12 000 patients in the celecoxib registration program (data on file, Pharmacia). No celecoxib study has shown an increased risk of MI compared with traditional NSAIDs.

The authors correctly assert there is "little clinical evidence from community use to suggest that selective COX-2 inhibition has serious unwanted effects other than those seen with standard NSAIDs", but imply there are few community data. In fact, community use of celecoxib in Australia (at least 1.5 million patients exposed) and worldwide (more than 20 million) has been extensive, and with this degree of exposure one would expect significant adverse event patterns to emerge. Reference to the Adverse Drug Reactions Advisory Committee and FDA database does not indicate a prothrombotic tendency of celecoxib. Further, we at Pharmacia do not consider that the four case studies presented by Cleland et al provide strong support for a prothrombotic tendency for celecoxib, especially as all patients described had diseases with high risk for thrombosis.

On the basis of a large body of controlled trial data (including CLASS) and extensive community exposure, the evidence does not show any more thrombosis with celecoxib than with NSAIDs.

Results of the CLASS and VIGOR studies clearly differ. It is clinically unjustified and scientifically unsound to suggest that rates of MI seen with rofecoxib can be ascribed to celecoxib and described as a "class effect".