Study Identifies Patients Who Should Avoid Arthritis Drug Class

Specific type of non-steroidal anti-inflammatory drugs can increase heart attack risk for some people.

An arthritis drug class that can increase the risk of heart attacks for some patients may return to prominence following the discovery of biomarkers that indicate which people should avoid them.

In a study recently published in the journal Circulation, researchers evaluated how a type of non-steroidal anti-inflammatory drugs (NSAID) known as COX-2 inhibitors can increase the risk of heart attacks for certain people. COX-2 inhibitors, including Vioxx and Celebrex, were linked to an increased heart attack risk that caused them to fall out of favor, while some brands like Vioxx were withdrawn.

"Although the majority of arthritis sufferers could safely use COX-2 inhibitors, the fear of heart attacks has left some patients confused and worried about their medication and GPs nervous about prescribing them,” researcher Jane Mitchell, of Imperial College in London, said in a press release. “This problem is made worse because we now know that most NSAIDs, not just COX-2 selective drugs, carry a similar risk of heart attacks in some patients. If we could identify which people have an increased risk, these patients could be offered more appropriate treatments, and we can start to look at ways of reducing or averting the risk entirely."

NSAIDs prevent the production of prostaglandins, which are produced by the COX-1 and COX-2 enzymes found at the site of inflammation, in addition to various other sites around the body. The study examined how the removal of COX-2 alters gene activity in mice. The researchers found that removing the COX-2 enzyme led to changes in 3 genes located in the kidney.

These changes predicted an increase in levels of the ADMA molecule, which is linked to cardiovascular disease. Additional testing revealed that taking NSAIDs caused in increase in ADMA levels in mice and in 16 human volunteers.

''ADMA is an independent risk factor for cardiovascular disease. In people increases of ADMA similar to those we found are linked with significant increases in cardiovascular disease and death,” researcher James Leiper, MD, said in a press release. “Our discovery that COX-2 inhibitors raise ADMA levels provides a plausible mechanism for the increased cardiovascular risk associated with these drugs and provides insights into how this risk might be mitigated.”

The researchers are planning a clinical trial to evaluate whether higher ADMA levels can function as an indicator of which patients face an increased heart attack risk.

"If we are right ADMA could be used as a biomarker in a simple blood test to identify who may be at risk, and regular screening would allow GPs to monitor patients' ADMA levels to ensure these remain within safe limits whilst taking the drug," Mitchell said.