BackgroundCOX-2 selective nonsteroidal anti-inflammatory drugs are prescribed for the treatment of arthritis and other musculoskeletal complaints because of their reduced gastrointestinal toxicity compared with traditional, nonselective NSAIDs. Questions about cardiovascular risk with these newer agents were raised by the finding of a 4-fold difference in the incidence of acute myocardial infarction between patients treated with rofecoxib compared with naproxen. Given the high utilization of COX-2 agents, even a small difference in cardiovascular risk between members of this class would have substantial public health impact.
Purpose The purpose of this study was to examine if COX-2 inhibitors are associated with an increased risk of cardiovascular events. And if that’s the case, is this a class adverse effect, and what could be the mechanism?
Results/ConclusionsThe development of COX-2 inhibitors as anti-inflammatory agents without gastric toxicity is based on the premise that COX-1 predominates in the gastric mucosa and yields protective prostaglandins, whereas COX-2 is induced in inflammation and leads to pain, swelling and discomfort. However, selective COX-2 inhibitors decrease vascular prostacyclin (PGI2) production without affecting the COX-1-mediated production of prothrombotic thromboxane A2, and may thus affect the balance between prothrombotic and antithrombotic eicosanoids.
My findings clearly confirm that COX-2 inhibitors are associated with an increased risk of cardiovascular events, in particular in patients with a history of cardiovascular disease. All COX-2 inhibitors available today have shown an increased tendency to induce cardiovascular events, and available data clearly suggest a class effect.