MONDAY. Aug. 27 (HealthDay News) -- Researchers believe they've zeroed in on what caused Vioxx to bring up users' heart risks.
The popular hurt reliever was taken off the merchandise in 2004 because it was linked to a high assay 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 decrease pain. But it also increases the production of a protein called tissue factor (TF) which can in help create 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 aggroup reported in the Aug. 27 online edition of The Journal of Experimental care for.
"We give a mechanism to understand the align effects caused by cox-2 inhibitors," said bring about researcher Mallika Ghosh a affix doctorate fellow at the university's Center for Vascular Biology in the department of cell biology at the University of Connecticut Health bear on.
Previously the increased cardiovascular assay 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 alter explanation for the added risk.
"We open 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 open they could decrease the high levels of TF in cox-2-treated mice by using TF-reducing agents. It may be possible to alter cox-2 inhibitors safer by giving TF-blocking drugs along with these pain killers the researchers proposed.
"If we can extend our bring home the bacon in humans and reduce TF levels then we can decrease the risk of these align effects," Ghosh said. "In addition measuring levels of TF could back up identify people at high risk for cardiovascular align effects from cox-2 inhibitors," she said.
Ghosh believes the TF-linked assay applies to all cox-2 inhibitors not just Vioxx or Bextra which was also taken off the market in 2005. A third cox-2. Celebrex remains on pharmacy shelves.
"Patients be to be careful when they take these medications especially if they have a history of cardiac problems," she said.
This same risk may also bear on to traditional pain medications called non-steroidal anti-inflammatory drugs (NSAIDs) such as Aleve and ibuprofen (brand named Advil. Motrin). Ghosh said. "No one has looked at what happens if you act high doses of NSAIDs," she said.
One expert believes that more chew over is needed however change surface when it comes to the cox-2s.
"We have always assumed that the problem with cox-2 inhibitors was linked to prostacyclin," said Dr. Steven E. Nissen chairman of the department of cardiovascular care for at the Cleveland Clinic and a noted expert on the drugs. "These [data] are suggesting that there may be more to the cardiovascular assay of cox-2 inhibitors and it may cerebrate to TF," he said.
However blocking TF to negociate that risk is comfort speculative. Nissen said. "The problem is that there are no approved TF-blockers so it's not even feasible to believe this," he said.
In addition it still isn't definite that TF is an important mechanism in humans linking cox-2 inhibitors with cardiovascular risk. Nissen said.
"This chew over is very speculative very preliminary," he said. "The finding needs to be confirmed in clinical trials."
SOURCES: Mallika Ghosh. Ph. D. affix doctorate fellow. bear on for Vascular Biology department of cell biology. University of Connecticut Health bear on. Farmington; Steven E. Nissen. M. D. chairman department of cardiovascular medicine. Cleveland Clinic. Ohio; Aug. 27. 2007. The Journal of Experimental Medicine online
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