Mukherjee and colleagues state that there is no definitive evidence that naproxen has a cardioprotective effect despite the results of 3 recent observational studies in the ARCHIVES.1- 3 They cite the results of a very large observational study by Ray et al4 in which the incidence of coronary heart disease (defined as acute myocardial infarction or coronary heart disease death) was the same in patients using NSAIDs as in patients matched for age and sex not taking NSAIDs. Furthermore, they reported that the incidence of coronary heart disease was the same in patients taking naproxen as in those not taking an NSAID. However, the use or nonuse of over-the-counter aspirin was not known in this observational study. The use or nonuse of aspirin in patients with cardiovascular indications for its use is critically important. In the CLASS trial,5 patients were allowed to take aspirin in addition to the study medication. There was no difference in the incidence of myocardial infarction in those taking the COX-2 inhibitor celecoxib than in those taking a nonselective NSAID (ibuprofen or diclofenac). In the VIGOR study,6 patients were not allowed to take aspirin. The incidence of myocardial infarction was higher in those taking a COX-2 inhibitor (rofecoxib) than in those taking a nonselective NSAID (naproxen). Nearly 40% of the myocardial infarctions in the VIGOR study occurred in the 4% of patients enrolled in the study who had a cardiovascular indication for aspirin but were not taking aspirin.
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