Bloomberg-Scientists may have discovered why painkillers such as Merck & Co’s Vioxx, taken off the market two years ago, can increase the risk of heart attack and stroke.

The drugs, which block the Cox-2 enzymes that are expressed in inflamed parts of the body, also inhibit the Cox-1 enzyme in cells that line blood vessels, researchers at two London medical colleges said in a study in the December issue of the Federation of American Societies for Experimental Biology journal.

By suppressing Cox-1, the drugs slow the production of the blood-thinning substance prostacyclin and thus heighten the heart risks, said scientists including Jane Mitchell, a professor at Imperial College London. They found that the drugs only had an adverse effect on Cox-1 in endothelial cells, which line blood vessels, and not in other areas such as platelets. They also saw no evidence of Cox-2 in these cells, findings that contrast with conventional scientific thinking about how the drugs work.

It is essential that we have a true understanding of their sites of action so that we can produce new, safe and effective drugs for years to come, said Tim Warner, a professor at the William Harvey Research Institute at Queen Mary University of London, one of the sthdys authors. This research will help us define such new drugs.

The risks of Cox-2 inhibitors, as the medicines are known, were thought to arise because the drugs blocked Cox-2 in the blood vessel cells. The findings may help scientists to develop new therapies that still focus on Cox-2, but which do not have an adverse effect on Cox-1 in the cells, the researchers said.

Cox-2 inhibitors, which also include Pfizer Inc’s Celebrex and Novartis AG’s Prexige, were developed as an alternative to treatments including ibuprofen and aspirin, which can harm the stomach, The drugs came under intense scrutiny by regulators in the U.S. and Europe after Merck with-drew Vioxx because the medicines are taken by millions of people to heat pain for long periods of time.

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