Study Points to Cause of Vioxx Heart Risk

The drug ups levels of a protein linked to clotting, researchers say.

By Steven Reinberg
HealthDay Reporter
Monday, August 27, 2007; 12:00 AM

Copyright © 2007 ScoutNews, LLC. All rights reserved.

MONDAY, Aug. 27 (HealthDay News) -- Researchers believe they've zeroed in on what caused Vioxx to boost users' heart risks.

The popular pain reliever was taken off the market in 2004 because it was linked to a high risk of heart attack and stroke.

In experiments with mice, the researchers have found that when cox-2 inhibitors like Vioxx block the cox-2 enzyme, it does reduce pain. But it also increases the production of a protein called tissue factor (TF), which can in help initiate unwanted clotting.

Since heart attacks and strokes are triggered by blood clots, it is possible that the overproduction of TF is, in part, responsible for cox-2 inhibitors' dangerous side effects, the University of Connecticut-led team reported in the Aug. 27 online edition of The Journal of Experimental Medicine.

"We provide a mechanism to understand the side effects caused by cox-2 inhibitors," said lead researcher Mallika Ghosh, a post doctorate fellow at the university's Center for Vascular Biology in the department of cell biology at the University of Connecticut Health Center.

Previously, the increased cardiovascular risk associated with cox-2 inhibitors was linked to prostacyclin, another protein important for preventing clotting. It's been shown that cox-2 inhibitors do lower prostacyclin levels.

However, Ghosh's team now proposes an alternate explanation for the added risk.

"We found increased levels of TF in the blood, heart and lungs in mice treated with a cox-2 inhibitor," Ghosh said. "With this mechanism, we can understand why cox-2 inhibitors contribute to the development of cardiovascular events," she said.

The researchers found they could reduce the high levels of TF in cox-2-treated mice by using TF-reducing agents. It may be possible to make cox-2 inhibitors safer by giving TF-blocking drugs along with these pain killers, the researchers proposed.

"If we can extend our work in humans and reduce TF levels, then we can reduce the risk of these side effects," Ghosh said. "In addition, measuring levels of TF could help identify people at high risk for cardiovascular side effects from cox-2 inhibitors," she said.