The cardiovascular toxicity of selective and nonselective cyclooxygenase inhibitors: Comparisons, contrasts, and aspirin confounding

The premature suspension of the Alzheimer Disease Antiinflammatory Prevention (ADAPT) and the Adenorna Prevention with Gelecoxib (APC) trials prompted intense review of the cardiovascular safety profile of selective and nonselective cyclooxygenase (COX) inhibitors. This article reviews the current state of selective COX-2 inhibitors, discusses the mechanistic evidence underlying the cardiovascular risk associated with selective COX-2 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-associated adverse cardiovascular outcomes in the ADAPT trial. Finally, recommendations regarding selective COX-2 inhibitors and appropriate timing of aspirin coadministration with traditional NSAIDs are proposed in relevance to patient safety and future trial design. (c) 2005 the American College of Clinical Pharmacology.