Which of the following NSAIDs is a selective COX-2 inhibitor that was withdrawn from the market due to increased cardiovascular risk?

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## COX-2 Selective Inhibitors and Cardiovascular Risk **Key Point:** Rofecoxib (Vioxx) was a selective COX-2 inhibitor withdrawn from the global market in 2004 due to significantly increased risk of myocardial infarction and stroke, particularly with long-term use. ### Mechanism of Cardiovascular Toxicity Selective COX-2 inhibition leads to: 1. Reduced prostacyclin (PGI₂) production in vascular endothelium → vasodilation loss 2. Unopposed thromboxane A₂ (TXA₂) activity in platelets → prothrombotic state 3. Net result: increased thrombotic risk and hypertension ### COX-2 Selective Inhibitors — Comparison | Drug | Status | Key Feature | | --- | --- | --- | | Rofecoxib | **Withdrawn (2004)** | Highest CV risk; complete COX-2 selectivity | | Celecoxib | Still available | Lower CV risk; partial selectivity; used with caution | | Etoricoxib | Available (outside US) | Moderate CV risk; used in some countries | **High-Yield:** The rofecoxib withdrawal was a landmark pharmacovigilance event that changed NSAID prescribing globally. This is a **must-know** fact for NEET PG. **Clinical Pearl:** Non-selective NSAIDs (like naproxen) inhibit both COX-1 and COX-2, so they suppress both TXA₂ and PGI₂ more evenly, reducing the net prothrombotic effect compared to selective COX-2 inhibitors. ### Current Clinical Practice - **Celecoxib** is the only COX-2 selective inhibitor still widely available; used at lowest effective dose for shortest duration - Non-selective NSAIDs preferred in patients with high cardiovascular risk - All NSAIDs carry some CV risk; gastroprotection with PPI recommended for long-term use