The cardiovascular toxicity of selective and nonselective cyclooxygenase inhibitors: comparisons, contrasts, and aspirin confounding.
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.
Konstantinopoulos
Panagiotis A
PA
SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Lehmann
David F
DF
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D015986:Confounding Factors, Epidemiologic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use; D011422:Propionates / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D016032:Randomized Controlled Trials as Topic
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D011422:Propionates; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C029658:propionic acid; D001241:Aspirin