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Chemical imbalance may explain painkiller's cardiac danger

The increased rate of cardiovascular complications in patients taking the cox-2 inhibitor painkiller rofecoxib (Vioxx) may result from a chemical imbalance, according to an animal study in the September Cell Metabolism. The findings suggest that low-dose aspirin might prevent the cardiac damage of such drugs and might also lead to the development of new anti-inflammatory drugs without the adverse side effects, the researchers said.

Earlier studies in humans have found that cox-2 inhibitors cause a decline in prostacyclin, a chemical that normally keeps blood vessels open and prevents blood clots. That drop occurs without a change in concentration of thromboxane, a related agent that constricts vessels and promotes clot formation.

The new study by researchers at Duke University and Durham VA Medical Centers found that, in mice prone to high blood pressure, an inability to respond to prostacyclin led to cardiac complications, including hypertension, enlarged hearts and severe scarring of the heart. Moreover, they showed, unrestrained action of thromboxane in the absence of prostacyclin accentuated the intensity of cardiac damage caused by the high blood pressure.

"The current results suggest that such a chemical imbalance in patients taking selective cox-2 inhibitor painkillers may present a cardiovascular hazard--particularly for people already predisposed to high blood pressure," said study author Thomas Coffman.

"Hypertension is the most common cardiovascular complication associated with cox-2 inhibition, yet not everybody who takes the drugs develops high blood pressure," he continued. "The mice appear to have characteristics similar to the subset of patients who are prone to experience this side effect."

Cox-2 inhibitors and other nonsteroidal, anti-inflammatory drugs (NSAIDs)--including aspirin and ibuprofen--all reduce inflammation and pain by blocking the function of cyclo-oxygenases, also known as cox enzymes. The cox e
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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
13-Sep-2005


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