Which NSAIDs are associated with the highest cardiovascular risk?

COX-2 selective NSAIDs are associated with higher cardiovascular risks primarily because of their mechanism of action. While COX-2 inhibitors were developed to minimize gastrointestinal side effects by selectively inhibiting the COX-2 enzyme—responsible for inflammation and pain—they also impact cardiovascular function. This selectivity can lead to an imbalance in the production of prostaglandins, favoring those that promote vasoconstriction and platelet aggregation, thereby increasing the risk of cardiovascular events such as heart attacks and strokes.

Clinical trials, particularly those assessing drugs like rofecoxib and valdecoxib, highlighted these risks, leading to significant concerns regarding their usage, especially in individuals with pre-existing cardiovascular conditions or risk factors. The understanding that while all NSAIDs can carry cardiovascular risks, COX-2 selective inhibitors have a notably higher association with adverse cardiovascular outcomes is crucial for clinical decisions regarding pain management in patients at risk.