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New Clues to COX-2 Drugs' Heart Effect?

Posted on: Tuesday, 18 April 2006, 12:00 CDT

Researchers said they have done animal studies that shed light on how COX-2 inhibitor pain drugs Vioxx and Celebrex affect the heart.

The research team at the University of Pennsylvania School of Medicine said they studied the drugs in multiple genetically manipulated mice and found that actions including genetic disruption of COX-2 and inhibition of the enzyme by different inhibitors seem to lead to a predisposition to clotting and an elevation of blood pressure.

In the study, the researchers compared genetically engineered mice that mimicked the impact of either COX-2 inhibitors or low-dose aspirin with healthy mice treated with COX-2 inhibitors, such as Celebrex.

However, in contrast to the negative effects on blood pressure caused by disruption of COX-2, the team also saw that deletion of another enzyme, mPGES-1, did not predispose the animals to thrombosis or elevate blood pressure.

Selective inhibitors of mPGES-1 may retain much of the benefit of drugs like Vioxx and Celebrex, while diminishing the risk of heart attack and stroke by having precisely the opposite effect on prostacyclin, said lead study author Garret FitzGerald, director of Penn's Institute for Translational Medicine and Therapeutics.

Although these results are in mice, not people, they raise an exciting possibility which can be tested in humans, he said.

The findings appear in the April 13 advanced online edition and May print issue of The Journal of Clinical Investigation.

Source: United Press International

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