Vioxx's heart risk tied to clotting effect

The anti-inflammatory drugVioxx may cause heart attacks and strokes because of itsblood-clotting effect, British scientists say.

The drugs, called COX-2 inhibitors, are primarily used to treat pain inconditions such as arthritis. They work by blocking theCOX-2 enzyme, which is expressed at sites of inflammationand underlies the production of hormones calledprostaglandins, which swell the joints and cause thefeeling of pain.

The medications also block the COX-1 enzymethat linesblood vessels, the team reported in the December issue of the Federation of American Societies for Experimental Biology (FASEB) journal.

The arthritis medication Vioxx was pulled form shelves in 2004 because of the health risks. Other COX-2 inhibitors such as Celebrex carry strong warnings about possible side-effects.

Prof. Jane Mitchell from the National Heart and Lung Institute at Imperial College London and her colleagues found that if COX-1 is blocked, blood may clot, boosting the risk of heart attack or stroke if the drugs are taken regularly.

"Our new research is exciting because it means we can work on developing better COX-2 inhibitors that don't pose the same risks in terms of heart attacks and strokes," Mitchell said.

Previously, scientists thought the side-effects of COX-2 inhibitors were tied to blocking the enzyme in the endothelium, which lines blood vessels.

Mitchell's team found no evidence of COX-2 in the endothelium. The side-effect was on COX-1 in endothelial cells but not other areas, such as platelets, the researchers said.

The study was based on an analysis of human blood vessels, blood and cells.

The researchwas funded by the British Heart Foundation, the Spanish government and a grant from the European Community.