Celecoxib selectively inhibits COX-2. Paradoxically, COX-2 selective inhibitors increase cardiovascular risk. The mechanism for this increased risk is:

• A Direct vasoconstriction via inhibition of COX-2 in vascular smooth muscle
• B Increased leukotriene synthesis causing platelet aggregation
• C Inhibition of COX-2-derived prostacyclin (PGI2) in endothelium while sparing COX-1-derived thromboxane A2 in platelets ✓
• D Inhibition of COX-2-derived PGE2 that normally prevents platelet aggregation

Explanation

Endothelial COX-2 produces prostacyclin (PGI2), which inhibits platelet aggregation and causes vasodilation. Platelet COX-1 produces thromboxane A2 (TXA2), which promotes aggregation and vasoconstriction. COX-2 selective inhibitors suppress endothelial PGI2 production while leaving platelet TXA2 production (via COX-1) intact, tipping the balance toward prothrombotic and vasoconstrictive effects. This imbalance explains increased risk of MI and stroke with selective COX-2 inhibitors.

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

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