## COX-2 Selective Inhibitors and Cardiovascular Risk **Key Point:** Rofecoxib (Vioxx) was a selective COX-2 inhibitor withdrawn from the market in 2004 due to significantly increased risk of myocardial infarction and stroke, particularly with prolonged use. ### Mechanism of Cardiovascular Risk Selective COX-2 inhibition leads to: 1. Reduced prostacyclin (PGI₂) production in vascular endothelium 2. Preserved thromboxane A₂ (TXA₂) production in platelets 3. Net prothrombotic state with unopposed platelet aggregation 4. Increased vasoconstriction and atherothrombotic events ### Comparison of NSAIDs by COX Selectivity | NSAID | COX Selectivity | Cardiovascular Risk | Market Status | | --- | --- | --- | --- | | Rofecoxib | COX-2 selective | High (withdrawn) | Withdrawn globally | | Celecoxib | COX-2 selective | Moderate (restricted) | Available with warnings | | Indomethacin | Non-selective | Moderate | Available | | Naproxen | Non-selective | Relatively lower | Available | | Ibuprofen | Non-selective | Moderate | Available | **High-Yield:** Rofecoxib withdrawal is a landmark pharmacovigilance event in NEET PG — frequently tested as a fact-based recall question. **Clinical Pearl:** Among NSAIDs, naproxen has shown relatively better cardiovascular safety profile compared to other non-selective NSAIDs in some studies, though all NSAIDs carry some cardiovascular risk. [cite:KD Tripathi 8e Ch 12]
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