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The once popular cox-2 drugs, Vioxx and Bextra, were pulled off the market in 2004 and 2005, respectively, after research showed that both raised the chances of cardiovascular trouble. Meanwhile, Celebrex, a painkiller in the same drug class that remains on the market, carries a "black box" warning alerting patients to potential heart risks.
Now, a team of scientists from the University of Pennsylvania in Philadelphia say that, although cox-2 inhibitors are very good at inhibiting the workings of the cox-2 enzyme -- and thereby easing pain -- they also throw off the cardiovascular system's delicate balance by inhibiting an enzyme that relaxes blood vessels and guards against clotting.
"It's really about a rock and a hard place," said Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital in Boston. "There's a balance in the bloodstream of clotting and vasoconstriction, as well as protection against clotting and vasodilation, which means that there's a constant balance of clotting and preventing clotting, and constricting arteries and dilating arteries."
"But with cox-2 inhibitors, they have found that you knock the protective side of that balance off," Cannon said. "And then you're left only with the constrictive part, which means the drugs up the risk for clotting and arterial constriction."
"This problem is bigger than just Vioxx, which no longer exists," he added. "It applies to every single NSAID (non-steroidal anti-inflammatory drug), because with all NSAIDs -- including Celebrex and ibuprofen, which zillions of people take -- the same issue exists. You block out the good stuff and leave the bad stuff unchecked. The one exception is Naproxen, which has an anti-platelet effect that seems to work against stroke and heart attack risk."
"Sometimes you have to take a cox-2 because you have really bad daily pain," said Cannon. "But this is a dose-dependent problem, with the more cox-2 you take the greater the cardiovascular risk. So you have to limit the dose and take the least amount you can get away with, so you can try to control crippling pain but also try not to poison your blood vessels and predispose yourself to clotting and high blood pressure."
The latest research was led by Dr. Garret FitzGerald, chairman of Penn's department of pharmacology and director of the Institute for Translational Medicine and Therapeutics. He and his colleagues published their findings in the May 2 issue of the journal Science Translational Medicine and the April 9 online issue of the Proceedings of the National Academy of Sciences.
-- Alan Mozes
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