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This article reviews the current state of selective COX\u20102 inhibitors, discusses the mechanistic evidence underlying the cardiovascular risk associated with selective COX\u20102 inhibition, outlines the pharmacodynamics of aspirin effects on platelets and the interference of propionic acid derivatives (ibuprofen and naproxen) with these effects, and poses that aspirin confounding may have led to the erroneous conclusion of naproxen\u2010associated adverse cardiovascular outcomes in the ADAPT trial. 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