Which of the following NSAIDs is a selective COX-2 inhibitor that was withdrawn from the market due to increased risk of thrombotic cardiovascular events?

Explanation

## COX-2 Selective Inhibitors and Cardiovascular Risk **Key Point:** Rofecoxib (Vioxx) was a selective COX-2 inhibitor withdrawn from the global market in 2004 due to significantly increased risk of myocardial infarction and stroke, particularly with prolonged use and in patients with pre-existing cardiovascular disease. ### Mechanism of Cardiovascular Toxicity Selective COX-2 inhibition leads to: 1. Reduced prostacyclin (PGI₂) production in vascular endothelium — a vasodilator and platelet aggregation inhibitor 2. Preserved thromboxane A₂ (TXA₂) production in platelets — a vasoconstrictor and pro-aggregatory agent 3. Net result: prothrombotic state with increased risk of arterial thrombosis ### Comparison of NSAID Classes | NSAID Class | Examples | COX Selectivity | Cardiovascular Risk | |---|---|---|---| | Selective COX-2 inhibitors | Rofecoxib, Celecoxib | High COX-2 selectivity | **High** (rofecoxib withdrawn) | | Non-selective NSAIDs | Ibuprofen, Naproxen, Indomethacin | Inhibit both COX-1 and COX-2 | Moderate (dose-dependent) | | Preferential COX-2 inhibitors | Meloxicam, Piroxicam | Moderate COX-2 preference | Lower than selective inhibitors | **High-Yield:** Rofecoxib withdrawal is a landmark pharmacovigilance event frequently tested in NEET PG. The mechanism involves the **prothrombotic imbalance** created by selective COX-2 inhibition. **Clinical Pearl:** Celecoxib, another selective COX-2 inhibitor, remains available but with strict cardiovascular risk warnings and contraindications in patients with established coronary artery disease or recent MI. [cite:KD Tripathi 8e Ch 12]