Genes Could Highlight Plavix Users at Clot Risk After Stent

Three gene types in heart patients and certain medications affected risk of dangerous clots

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TUESDAY, Oct. 25 (HealthDay News) -- Scientists have identified mutations in three genes that make certain patients more likely to have a potentially fatal blood clot after undergoing heart stent placement.

The genes are involved in metabolism of the drug Plavix (clopidogrel), a widely used blood thinner, and in platelet formation, according to a study published in the Oct. 26 issue of the Journal of the American Medical Association.

"This goes back to the idea of tailored medicine but [gene testing] is not feasible to do on everybody," said Dr. John Gassler, associate professor of medicine at the University of Rochester Medical Center, who was not involved with the research. "This study is very strongly thought-provoking but I don't think it can alter practice until it's been evaluated [further]."

The authors of the study also reported that a higher initial dose of Plavix reduced the risk of stent thrombosis (blood clot formation), while using proton pump inhibitors -- common drugs to treat gastroesophageal reflux disease (GERD) and stomach ulcers -- upped the risk.

People who get stents to prop open blocked arteries routinely receive two different blood thinners to reduce the risk of stent thrombosis. This has cut the rate of stent thrombosis tremendously, but up to 4 percent of patients still end up with this devastating complication, according to background information in the study.

The study authors analyzed 23 gene variants in 15 genes in 123 patients who had undergone percutaneous coronary intervention in France and who had experienced stent thrombosis.

These patients were compared to 246 similar patients who had not had stent thrombosis.

Three genotypes and two clinical factors -- Plavix loading (initial) dose and use of proton pump inhibitors -- all affected the risk of stent thrombosis.

When the investigators combined the clinical and risk factors, they found that those in the highest risk category had a sevenfold increased risk of stent thrombosis versus patients with the lowest risk profile.

"When we combine everything we have a very good predictive value, which is around 80 percent," said study co-first author, Dr. Jean-Sebastien Hulot, director of Pharmacogenomics & Personalized Therapeutics of the Cardiovascular Research Center at Mount Sinai School of Medicine in New York City.

But while the clinical variables are easy enough to assess, genetic information is not so easy to come by, at least not yet. Right now, results of genetic tests take about a week to come back.

"It would make sense to have the results in a couple of hours and some companies are developing this kind of testing," Hulot said. "In the near future we can have the results in hours. The markers aren't valuable right now but they will be in the near future."

SOURCES: John Gassler, M.D., associate professor of medicine, University of Rochester Medical Center, Rochester, N.Y.; Jean-Sebastien Hulot, M.D., Ph.D., associate professor of medicine and director, Pharmacogenomics & Personalized Therapeutics, Cardiovascular Research Center, Mount Sinai School of Medicine, New York City; Oct. 26, 2011, Journal of the American Medical Association

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