Which NSAID class is associated with lower GI risk but higher cardiovascular risk?

• A. COX-2 selective inhibitors
• B. Nonselective NSAIDs
• C. Acetaminophen
• D. Opioids

Answer: (A)

NSAIDs work by inhibiting two enzymes, COX-1 and COX-2, which have different roles. Inhibiting COX-1 disrupts the protective lining of the stomach, increasing the risk of ulcers and GI bleeding; this is why nonselective NSAIDs, which block both COX-1 and COX-2, tend to raise GI risk. In contrast, COX-2 selective inhibitors spare COX-1, so GI protection remains better and GI injury is reduced. However, COX-2 also drives production of prostacyclin (PGI2) in the vessels, which helps prevent clotting. Blocking COX-2 lowers PGI2 without equally affecting thromboxane A2, tipping the balance toward a pro-thrombotic state and raising cardiovascular risk. So COX-2 selective inhibitors are associated with lower GI risk but higher cardiovascular risk.