In a recent Canadian Adverse Reaction Newsletter1 issued by Health Canada, the authors recommend that “caution should be exercised in prescribing [selective COX-2 inhibitors] to patients at risk of cardiovascular disease.” To make such a recommendation based on the adverse reactions presented in the newsletter is not scientifically rigorous. The data are not adjusted for exposure, and thus are unlikely to represent an accurate evaluation of cardiovascular risk.
The impetus behind this article appears to be a meta-analysis by Mukherjee and colleagues,2 which is methodologically flawed3,4,5 and does not form an appropriate basis for public health recommendations.
Certainly the increased rate of adverse cardiovascular events, as demonstrated in the VIGOR study for rofecoxib,6 warrants further investigation. Clinical data available for celecoxib, however, demonstrate that patients on celecoxib are no more at risk of cardiovascular events than patients taking traditional NSAIDs such as ibuprofen, diclofenac or naproxen.7 This observation holds true even at supratherapeutic doses, as demonstrated in the CLASS trial.8,9
Differences in molecular structure and metabolism may partly explain the distinct cardiovascular safety profiles of the 2 coxibs, and this hypothesis should be examined further.10,11
If immediate recommendations are required, perhaps Health Canada would be more justified in suggesting that caution be exercised in prescribing these agents, particularly rofecoxib, to patients at high risk of cardiovascular disease. The implementation of such a policy should be individualized at the discretion of the treating physician in light of each patient's risk factor profile, the presence (if any) of diabetes and cardiovascular history.
John C. Peterson Cardiologist Toronto, Ont.
Competing interests: Dr. Peterson has spoken for the last 2 years at continuing medical education events for Novartis, Merck, Pharmacia and Abbott.
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