Celecoxib is a selective COX-2 inhibitor. The increased cardiovascular risk associated with selective COX-2 inhibitors (as seen with rofecoxib withdrawal) is mechanistically explained by:

• A Direct myocardial toxicity due to accumulation of arachidonic acid in cardiomyocytes
• B Increased platelet COX-1 activity leading to excess TXA2 production
• C Suppression of prostacyclin (PGI2) synthesis in endothelium without affecting platelet thromboxane A2 (TXA2), shifting the balance toward thrombosis ✓
• D Inhibition of prostacyclin-independent vasodilation via NO synthase blockade

Explanation

Prostacyclin (PGI2), made in vascular endothelium via COX-2, is antithrombotic and vasodilatory. Platelets produce thromboxane A2 (TXA2) via COX-1, which is prothrombotic and vasoconstrictive. Selective COX-2 inhibitors suppress endothelial PGI2 without reducing platelet TXA2 (which relies on COX-1), tilting the prostanoid balance in favour of thrombosis and vasoconstriction — increasing MI and stroke risk. This was the mechanism behind rofecoxib's withdrawal. Celecoxib is still marketed because it has modest COX-1 inhibition at therapeutic doses.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.