The increased risk of heart attack or stroke associated with many arthritis drugs may be avoidable, according to a new international study co-authored by researchers at Imperial College London.
Drugs such as Vioxx, diclofenac, ibuprofen and Celebrex operate by blocking an enzyme known as COX-2, whose presence in blood vessels has up until now been held responsible for these side effects. New research carried out on mice has revealed that COX-2 is largely absent from the major blood vessels and instead found in the brain, gut, and kidney as well as the thymus gland in the chest.
Now that researchers know where in the body the drug is acting, they can begin to develop safer, more targeted drugs for patients with arthritis as well as cancer.
Arthritis drugs have long been associated with potentially fatal cardiovascular side-effects in patients. Health concerns led to the anti-inflammatory Vioxx being withdrawn from the market in 2004, and this week medical regulators have advised some patients to stop using the painkiller diclofenac.
Researchers have always believed that COX-2 was found in the blood vessels where it was central to preventing the formation of clots. This meant that any drug that inhibited the enzyme was thought to lead to an increased risk of clotting.
The new study, published today in the journal PLOS ONE, reveals that COX-2 is largely absent from the major blood vessels. Instead COX-2 appears to be present in the brain, kidney, thymus and gut, where it may well be affecting the cardiovascular health.
Lead author, Professor Jane Mitchell of Imperial's Faculty of Medicine said: "Now we know the true sites of COX-2, we can begin to develop new ideas that will lead to better drugs for arthritis and cancer with fewer side effects."
The new research suggests future development of COX-2 inhibitors that carry reduced risk of stroke or heart attack may be possible. Professor Mitchell
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Imperial College London