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0647 Cardiovascular risk exists with both specific inhibitors and ‘historical’ NSAIDS Medicine prescribers have broad and probably increasing access to the COX-2 inhibitor meloxicam as a result of proliferation of generic products, and continued access to celecoxib which some years back heralded the arrival of a specific and safe treatment for inflammatory joint disease. One can only hope that while the focus of attention has been on claims laid against the manufacturer of Vioxx (rofecoxib) by chronically-treated patients who suffered cardiovascular events, medicine prescribers are fully aware of the fact that such side effects are common to the group of coxibs. Cyclo-oxygenase-2 inhibitors were developed to decrease the risk of gastrointestinal injury and avoid the anti-platelet effect of traditional NSAIDs. However randomised trials have shown an increased risk of thrombotic cardiovascular events with COX-2 inhibitors. Comparable long-term, placebo-controlled trials assessing the risk of thrombotic cardiovascular events with traditional NSAIDs have not been available, although results of observational studies suggested that some traditional NSAIDs (eg, diclofenac, ibuprofen) also increase cardiovascular risk. The MEDAL study, which was done between 2002 and 2006 at 1 380 sites in 46 countries, was designed to pool data from three randomised, double-blind clinical trials. Results showed that patients treated with the COX-2 selective NSAID etoricoxib and those given the traditional NSAID diclofenac had near-identical rates of thrombotic cardiovascular events. The most plausible explanation for the cardiovascular hazard conferred by NSAIDs selective for COX-2 and by some traditional NSAIDs is the suppression of prostacyclin, which constrains endogenous mediators of platelet activation, hypertension, atherogenesis, and cardiac dysfunction. Only aspirin, which irreversibly inactivates platelet COX-1, has this property to an acceptable extent. All other reversible COX inhibitors (traditional and selective) inhibit platelet COX-1 insufficiently to afford cardioprotection, except perhaps naproxen in some individuals. While these data are clearly more relevant in the adult population, certain paediatric chronic inflammatory conditions merit consideration of the results. |