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UM doctors want more patients tested for gene variant that makes heart drug ineffective

Emma Dorsey Barnes thought her health would improve after doctors placed stents in two clogged arteries to help boost blood flow to her heart.

But three years later the 74-year-old home health nurse found herself back in the operating room last spring in need of three more stents.


After the second procedure, her doctors at the University of Maryland Medical Center gave her a genetic test to determine if her body wasn't effectively responding to clopidogrel, the most common drug used to treat people after they get stents. It is commonly sold under the brand name Plavix.

Plavix is a blood thinner that prevents the blood from clotting around stents after surgery, which can reduce the risk of heart attack and stroke in people with heart disease. But the drug only works when a liver enzyme in the body activates it.


About 30 percent of people have at least one gene variation that might prevent this activation and make the drug less effective. Doctors discovered Barnes had the gene variant.

"I am absolutely glad they found out," she said. "I don't want to keep going through stent procedures."

Last summer, the University of Maryland Medical Center began routinely conducting the genetic test to patients who get stents to open clogged arteries. The tests extract a patient's DNA from a blood sample and identify whether they carry a variation in what is called the CYP2C19 gene. Without the test, doctors say, too many patients aren't getting the best treatment and are being put at risk for dangerous blood clots.

The Baltimore hospital is one of a small number nationwide to offer the genetic test, which it started doing as part of a research study involving several medical institutions looking at the benefits to patients.

The test is now part of the University of Maryland's routine care for stent patients, but it still is not the standard of care for all stent patients, even though the medical community has known about the gene variation for years.

Starting in 2010, the U.S. Food and Drug Administration required a black-box warning, the strongest there is, on clopidogrel's packaging to make people aware of the genetic effect.

University of Maryland doctors hope the research they participated in will encourage other medical facilities to routinely offer the genetic test.

"We have been researching this a long time and now want to see it move to the clinic so that more patients get testing whenever they have a stent," said Dr. Amber L. Beitelshees, a study co-author and an assistant professor at the University of Maryland School of Medicine who specializes in pharmacogenomics.


As part of the study, researchers at Maryland and other universities created a database to compare the outcomes of 1,815 patients who had the genetic testing. About 250 of those patients were from the University of Maryland Medical Center or the Baltimore Veterans Affairs Medical Center.

After the genetic test, doctors were able to give patients with the gene variant a different medication. About 60 percent of patients were given the drug ticagrelor, according to results of the study reported at a science conference hosted by the American Heart Association. The researchers said changing treatment helped halve the rate of death, heart attack and stroke among study participants.

"It indicates strong evidence that there is a better alternative for some people," said Dr. Mark Vesely, an interventional cardiologist and associate professor of medicine at the University of Maryland School of Medicine, another co-author of the study.

Ticagrelor is absorbed directly into the bloodstream and begins working right away. But it also has to be taken twice a day and there is worry that patients might not adhere to that requirement. The drug is also more costly and has some side affects, such as shortness of breath, that may prevent doctors from prescribing it more widely, Vesely said.

Beitelshees said she also believes more hospitals are not yet offering the testing routinely because it is logistically taxing to change procedures. She noted that the University of Maryland has a translational genomics laboratory that that can do the genetic testing and report results, usually within 24 hours. Not all hospitals can perform the test as quickly, which is important when treating patients having a heart attack, Beitelshees said.

The researchers said larger studies need to be done to further boost their findings. Vesely would like to see research on whether it saves money over the long run to give patients ticagrelor, rather than prescribe Plavix only to have patients return to the hospital because the drug didn't work.


"I think there needs to be a study to show doing the genotyping and putting people on the right drug from the outset is cost effective," Vesely said.

Dr. Paul A. Gurbel and researchers at the Sinai Center for Thrombosis Research in Baltimore were among scientists who found in 2003 that some people don't respond to clopidogrel therapy. University of Maryland Medical School researchers along with Sinai researchers published a scientific paper in 2009 that identified the gene variants that cause the different reaction to the drug.

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Vesely said the researchers are not suggesting that people stop using Plavix in all cases.

"Plavix is still a very, very good drug," he said. "We have used it for a very long time."

Dorsey Barnes is glad there is an alternative.

She had never heard about a gene variation and didn't know that Plavix was not effective in all people. She was surprised that she was one of the people for whom it didn't work. She now takes a different drug and will get her heart checked every few months to make sure the new treatment is working.


"I had never heard about test. I had never heard about the gene. But I am glad I know about it now," she said.