Scientists believe they have uncovered why some arthritis drugs such as Vioxx can cause heart attacks and strokes.
Vioxx was taken off the market in 2004
They found Cox-2 inhibitor painkillers were stopping an enzyme producing blood-thinning agents - leading to a greater chance of blood clotting.
Vioxx and other Cox-2 inhibitors have been pulled from the market because of their risks to health.
The research is published in the journal of the Federation of American Societies for Experimental Biology.
After Vioxx was withdrawn in 2004, its manufacturer Merck was ordered to pay $253.4m (£141m) to the widow of a man who died from a heart attack blamed on the drug. The US pharmaceutical giant is currently facing thousands of law suits.
Other Cox-2 inhibitor drugs have since been withdrawn from the market or are accompanied by strong warnings of the possible damaging effects on health.
However, the precise mechanism of how this class of drug can boost the risk of heart attack or stroke has up to now remained unknown.
Now researchers from London believe they have found an answer.
Cox-2 inhibitors work by blocking the Cox-2 enzyme, thereby halting the production of hormones that swell the joints and cause pain.
But the team has discovered the inhibitors are also blocking an enzyme called Cox-1 inside of the cells that line blood vessels.
Within these cells, Cox-1 is responsible for producing a blood-thinning agent called prostacyclin, but if the enzyme is blocked, the blood may clot and heighten the risk of heart attack or stroke.
The researchers said the findings are significant because it may lead to the development of Cox-2 drugs which do not carry these side-effects.
Professor Jane Mitchell, an author of the study from the National Heart and Lung Institute at Imperial College London, said: "Cox-2 inhibitors can have great benefits for patients suffering from conditions such as arthritis and it would be great if they could remain available.
"However, the problem is that their use appears associated with an increased risk of heart attacks."
Professor Tim Warner, a co-author from Barts and the London at Queen Mary University of London, said: "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." Professor Alan Silman, the incoming medical director of the Arthritis Research Campaign, said it was important to pinpoint possible mechanisms for the side-effects of these drugs.
However, he added, the bigger picture was still not clear. Recent research, he said, had shown some Cox-2 inhibitor drugs did not seem to increase the risk of these side-effects while some of the traditional drugs did.
He said it was important to work out the reasons behind this.
The UK team believes their findings may help to develop drugs that do not have this side-effect.