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Med J Aust 2005; 182 (6): . || doi: 10.5694/j.1326-5377.2005.tb06692.x
Published online: 21 March 2005

The cardiovascular complications of cyclo-oxygenase-2 (COX-2) inhibitors appear to be a class effect, according to Dr Jeffrey Drazen, Editor-in-Chief of The New England Journal of Medicine (NEJM). Drazen was commenting on three research articles published on the NEJM website that report cardiovascular toxicity data for not only rofecoxib but also celecoxib, and valdecoxib and its intravenous prodrug, parecoxib. The data came from trials designed to test the efficacy of these agents for a variety of indications rather than associated risks. Data for celecoxib came from the Adenoma Prevention with Celecoxib study, a randomised, controlled trial involving 2035 patients in which celecoxib at a dose of 400 mg twice daily was associated with more than a tripling of the risk of cardiovascular events; 200 mg twice daily more than doubled the risk. US experts, who also commented on these results, say we know that COX-2 inhibitors inhibit the production of prostacyclin and favour vasoconstriction, which may increase the risk of cardiovascular events, including myocardial infarction, stroke, hypertension and heart failure. However, we lack adequate information to make confident statements about the exact levels of risk for each COX-2 inhibitor, the time course of the risk during therapy, and the population of patients, if any, in whom the benefits of therapy might exceed the risks. Drazen said it was reasonable to ask whether the use of COX-2 inhibitors can now be justified, given that there are well-established options for the treatment of all the approved indications for these drugs.



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