COX-2 inhibitors promote cardiovascular risk by selectively reducing vascular prostacyclin synthesis without disrupting COX-1-derived thromboxane synthesis.
Do COX-2 inhibitors increase cardiovascular risk?
This review highlights the mechanistic basis for the increased cardiovascular risk associated with COX-2 inhibitors, driven by an imbalance between prostacyclin and thromboxane.
Placebo-controlled trials of nonsteroidal antiinflammatory drugs (NSAIDs) selective for COX-2 have revealed an enhanced risk for cardiovascular events. COX-2 inhibitors (coxibs) selectively reduce vascular prostacyclin synthesis without disrupting COX-1-derived thromboxane synthesis in platelets. Removal of prostacyclin's capacity to restrain all known endogenous compounds contributing to platelet activation and vasoconstriction is a well-recognized mechanism for coxib action in the cardiovascular system which can pre-dispose to thrombosis, hypertension and atherosclerosis. Novel mouse models of selective COX-2 inhibition and disruption of microsomal prostaglandin E synthase-1 have been exploited to reveal the relative importance of prostacyclin and prostaglandin E2 in cardiovascular homeostasis. This review discusses the background to our current understanding of coxibs and provides further information relating to recent mechanistic insights into how COX-2 inhibition promotes cardiovascular risk.
Funk et al. (Thu,) conducted a review in Cardiovascular risk. COX-2 inhibitors was evaluated. COX-2 inhibitors promote cardiovascular risk by selectively reducing vascular prostacyclin synthesis without disrupting COX-1-derived thromboxane synthesis.