## COX-2 Selective Inhibitors **Key Point:** Celecoxib is a selective COX-2 inhibitor (coxib class) that preferentially blocks COX-2 while sparing COX-1. ### Mechanism of Cardiovascular Risk Selective COX-2 inhibition leads to: 1. Reduced prostacyclin (PGI₂) production in endothelium — a vasodilator and platelet aggregation inhibitor 2. Preserved thromboxane A₂ (TXA₂) production in platelets — a vasoconstrictor and pro-aggregant 3. Net prothrombotic state → increased risk of MI and stroke **High-Yield:** The COX-2 selective inhibitor class (celecoxib, rofecoxib [withdrawn], valdecoxib) carries a black-box warning for cardiovascular and thromboembolic events. Rofecoxib was withdrawn from the market in 2004 due to this risk. ### Comparison with Non-Selective NSAIDs | Feature | Selective COX-2 (Celecoxib) | Non-selective NSAIDs | |---------|---------------------------|---------------------| | COX-1 inhibition | Minimal | Yes | | COX-2 inhibition | Preferential | Yes | | GI ulcer risk | Lower | Higher | | CV thrombotic risk | **Higher** | Lower (balanced inhibition) | | Platelet function | Relatively preserved | Impaired | **Clinical Pearl:** Non-selective NSAIDs (ibuprofen, naproxen) inhibit both COX-1 and COX-2, so they reduce both TXA₂ and PGI₂ proportionally, resulting in a more balanced antiplatelet effect and lower net thrombotic risk compared to selective COX-2 inhibitors. **Warning:** Celecoxib is absolutely contraindicated in patients with prior MI, stroke, or established coronary artery disease due to the increased risk of recurrent thrombotic events.
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