A recent study may provide hope that scientists will one day be able to develop COX-2 inhibitor drugs, such as Celebrex and Vioxx, that do not have the associated risk of heart attacks and strokes. The research, published in the December issue of the Federation of American Societies for Experimental Biology (FASEB), found that Vioxx and the COX-2 inhibitors may cause heart attacks and strokes because of a blood clotting effect linked to the inhibition of the COX-1 enzyme.
The COX enzymes are naturally occurring and produce hormones called prostaglandins. The COX-1 enzyme is found in areas of inflammation and also in the stomach. In the stomach, the COX-1 enzyme is a good thing. It protects and enhances the natural mucous lining of the stomach. The COX-2 enzyme is not found in the stomach, only in areas responsible for inflammation.
Non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and naproxen inhibit both the COX-1 and the COX-2 enzymes, blocking inflammation, but also causing gastrointestinal problems such as upset stomach and ulcers. The COX-2 inhibitor drugs, like Vioxx, were developed to block only the COX-2 enzyme. Until most of them were pulled from the market by the FDA, they were widely promoted because they did not have the same GI side effects.
However, this new study by British researchers seems to contradict the widely published theory that the COX-2 drugs only block the COX-2 enzyme. They found that the drugs also block the COX-1 enzyme in the lining of blood vessels. When this happens, the blood may clot, increasing the risk of cardiovascular events such as heart attacks and strokes. This casts doubt on the previous theory that the drug side effects were tied to the COX-2 enzyme in endothelial cells (the layer of cells that lines the interior of blood vessels). The study however, found no evidence of the COX-2 enzyme in this layer of cells.
If the findings of this study are true, then I hope it will be able to take the development of safer NSAIDS in a new direction. So far, scientists have been unable to develop a COX-2 drug that isn’t linked to heart attacks and increased risk of death. Even Arcoxia, Merck’s potential Vioxx replacement, has shown in Merck’s study to cause heart attack, stroke, or death in 1% of the study patients after 18 months of taking the drug. The number increased to 2.5% by three years.
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Published On: January 17, 2007