Vioxx aspirin solution suggested

Vioxx was linked to heart problems

Correcting a chemical imbalance could make the controversial arthritis drug Vioxx safe to use, scientists suggest.

The US drug giant Merck withdrew Vioxx in September 2004 after evidence linking it to heart attacks and stroke.

Now a US team at Duke University says taking low-dose aspirin alongside Vioxx might prevent these side effects, the journal Cell Metabolism reports.

A Texan court recently found Merck guilty of negligence over its handling of Vioxx, prompting worldwide lawsuits.

Unwanted side effects

COX-2 inhibitors are more "stomach friendly" alternatives to traditional pain relief drugs called non-steroidal anti-inflammatory drugs (NSAIDs), which can sometimes cause side effects such as ulcers and bleeding.

They are used to treat pain and inflammation in arthritis and to relieve acute pain.

Since the heart safety concerns surrounding Vioxx and other COX-2 inhibitors were raised, researchers have been investigating how they might be avoided.

It may be possible to identify drugs that provide all the therapeutic effects of NSAIDs and COX-2 inhibitors but lack their adverse side effects Dr Matthew Breyer, from Vanderbilt University Medical School in the US

Dr Thomas Coffman, along with colleagues from the University of North Carolina, Pennsylvania University and Durham VA Medical Center, looked at some of the chemical processes that occur in the body in response to COX-2s.

COX-2s and other NSAIDs, including aspirin and ibuprofen, reduce inflammation and pain by blocking the function of enzymes called cyclo-oxygenases.

These enzymes normally produce chemicals called prostaglandins, such as prostacyclin, and thromboxanes.

Prostacylin keeps blood vessels open and prevents clots, while thromboxane constricts vessels and promotes clot formation.

COX-2 inhibitors cause a decline in prostacyclin without any change in thromboxane levels. In comparison, aspirin lowers both thromboxane and prostacyclin.

The US researchers found that in mice prone to high blood pressure and lacking normal prostacyclin activity - as occurs with COX-2s - developed enlarged, scarred hearts.

Chemical imbalance

In comparison, mice lacking normal activity of both thromboxane and prostacyclin continued to suffer from high blood pressure but did not develop heart complications.

This might suggest why people with high blood pressure taking COX-2s are at increased risk of heart attack and stroke.

It is likely that unopposed thromboxane is to blame, they said.

Adding in aspirin to lower thromboxane might help avoid unwanted heart problems, the researchers believe.

Dr Coffman said: "Our data suggests that therapies that block unrestrained thromboxane actions - for example, low doses of aspirin - might protect against end-organ damage without affecting blood pressure in patients taking COX-2 inhibitors."

However, he said it would be important to check that adding an aspirin-like therapy would not cause unwanted gastrointestinal side effects, such as bleeding.

Dr Matthew Breyer, from Vanderbilt University Medical School in the US, said: "It may be possible to identify drugs that provide all the therapeutic effects of NSAIDs and COX-2 inhibitors but lack their adverse side effects."

A spokeswoman for the Arthritis Research Campaign said the study provided a possible scientific explanation of why COX-2s increase the risk of heart attack and stroke.

Belinda Linden, head of medical information at the British Heart Foundation, said more research was needed.

"It would be ideal if we could keep the beneficial effects of these drugs whilst losing unwanted effects through combining treatments. This early study in mice is a step towards this goal," she said.