New avenue opens up to avoid cardiovascular side effects of COX inhibitors

Research lead

Researchers at Imperial College London have uncovered evidence for the mechanism by which COX-2 inhibitors such as Vioxx can cause heart attacks and strokes, opening up a new avenue for the development of drugs that do not have these side effects.

COX-2 inhibitors are primarily used to treat pain in conditions such as arthritis. They work by blocking the COX-2 enzyme, which is expressed at sites of inflammation and underlies the production of hormones called prostaglandins, which swell the joints and cause pain.

The researchers have discovered that although COX-2 inhibitors target only COX-2, they also inhibit the enzyme COX-1 within the endothelial cells that line all blood vessels. 

COX-1 in these cells makes prostacyclin, which thins the blood. Where this is inhibited there is a greater chance of blood clotting, increasing the risk of heart attacks and strokes.

It was thought previously that the side effects of COX-2 inhibitors were caused by inhibiting COX-2 in the endothelium and that this was reducing the production of blood-thinning agents.

The researchers found no evidence for the existence of COX-2 in the endothelium, meaning that selective COX-2 inhibitors should avoid the side effects seen with the current generation of inhibitors.

One of the researchers Jane Mitchell said the findings "mean we can work on developing better COX-2 inhibitors that don't pose the same risks in terms of heart attacks and strokes".

The research was funded by the British Heart Foundation, the Spanish Government and a European Community’s Framework Programme 6.