Key result
Aspirin confounding may have led to the erroneous conclusion of naproxen-associated adverse cardiovascular outcomes in the ADAPT trial, highlighting the need for careful NSAID coadministration.
This review highlights the cardiovascular risks of COX-2 inhibitors and emphasizes the importance of appropriate timing for aspirin coadministration with traditional NSAIDs to avoid confounding and adverse outcomes.
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May explain discrepant NSAID trial results; leaves open optimal aspirin coadministration strategies in high-risk patients.
The premature suspension of the Alzheimer Disease Anti-inflammatory Prevention (ADAPT) and the Adenoma Prevention with Celecoxib (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.
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Konstantinopoulos et al. (2005) conducted a review in Cardiovascular toxicity. Selective and nonselective cyclooxygenase (COX) inhibitors was evaluated. Aspirin confounding may have led to the erroneous conclusion of naproxen-associated adverse cardiovascular outcomes in the ADAPT trial, highlighting the need for careful NSAID coadministration.
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