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Other Coxibs May Increase Risk of Heart Attack 

October 13, 2004

By Ashley Starkweather, B.S. and Asher Kimchi M.D.

Los Angeles, CA - In a report to be published on October 21, 2004 in the New England Journal of Medicine, author Garret A. Fitzgerald suggests that Vioxx may not be the only drug of its type that raises the risk of heart attack and stroke.

Vioxx belongs to the class of drugs that selectively inhibits cyclooxygenase-2 (COX-2), an enzyme that produces prostaglandins E2 and I2, mediators of inflammation. By not inhibiting cyclooxygenase-1 (COX-1), whose products provide cytoprotection in the gastric epithelium, these coxibs were thought to decrease the incidence of gastric side effects when compared to traditional NSAIDS that inhibit both cyclooxygenases.

However, prostaglandin I2 has been shown to inhibit platelet aggregation, cause vasodilation and prevent the proliferation of vascular smooth muscle cells in vitro. It was previously thought that prostaglandin I2 was primarily a product of COX-1 in the endothelium, but more recent studies in mice and humans has shown that COX-2 is actually the dominant source.

The major product of COX-1 in platelets, thromboxane A2, has effects that directly oppose prostaglandin I2, causing platelet aggregation, vasoconstriction, and vascular smooth muscle proliferation.

Therefore, by selectively inhibiting COX-2, the vascular effects will be those of thromboxane A2, since prostaglandin I2 production has been inhibited. This could lead to increased risk of stroke or heart attack due to an exaggerated thrombotic response to the rupture of an atherosclerotic plaque. Other effects could include elevated blood pressure and accelerated atherogenesis.

Vioxx has been removed from the market by Merck. Dr. Fitzgerald suggests in this report that until the FDA determines whether these effects apply to this class of drugs as a whole, it would seem prudent to avoid coxibs in patients who have cardiovascular disease or who are at risk for it. 

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