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The Cardiovascular Toxicity of Selective and Nonselective Cyclooxygenase Inhibitors: Comparisons, Contrasts, and Aspirin Confounding
Author(s) -
Konstantinopoulos Panagiotis A.,
Lehmann David F.
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005278202
Subject(s) - aspirin , medicine , naproxen , celecoxib , cyclooxygenase , pharmacology , ibuprofen , adverse effect , confounding , clinical trial , pharmacodynamics , pharmacokinetics , chemistry , pathology , enzyme , biochemistry , alternative medicine
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.