COX-2 Inhibitors - Adverse Effects

Adverse Effects

Analysis of clinical trial data revealed that there was a significant increase in the rate of vascular events with COX-2 inhibitors compared with placebo; "vascular events" are non-fatal myocardial infarction (MI), non-fatal stroke, and death from a vascular event such as MI or stroke. These results led Merck to voluntarily withdraw (Rofecoxib) from the market in September 2004 and to regulatory authorities imposing black box warnings on the label of celecoxib. Traditional NSAIDs were also found to have cardiovascular risks, leading to similar black box warnings.

The cause of the cardiovascular problems became, and remains, a subject of intense research. As of 2012 results have been converging on the hypothesis that the adverse cardiovascular effects are most likely due to inhibition of COX-2 in blood vessels leads to a decrease in the production of prostacyclin in blood vessels. Prostacyclin usually prevents platelet aggregation and vasoconstriction, so its inhibition can lead to excess clot formation and higher blood pressure.

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