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Gene Ups Risk for Those on Blood-Thinner Plavix

Younger patients with the mutation faced higher odds of heart attack, death, study found

MONDAY, Dec. 22 (HealthDay News) -- A gene variation can make younger heart attack patients more prone to another heart attack, death or other heart problems if they receive the anti-clotting drug Plavix, researchers report.

The study is published in the Dec. 23 online edition of The Lancet.

Plavix plus low-dose aspirin are often used to prevent blood vessels from clogging after a heart attack or after patients receive an artery-opening stent.

But some patients do not do well on Plavix (clopidogrel). Until now, the reasons for that variance have been unclear.

Plavix "targets a very important receptor on platelets, but people vary substantially in how good an anti-clotting effect they have" from the drug, explained Dr. Robert F. Storey, from the Cardiovascular Research Unit at the University of Sheffield School of Medicine in the United Kingdom. He is also the author of an accompanying comment in the journal.

"The variation in response is partly due to genetics, but there are other factors such as age which influence the response," Storey said.

For the study, a team led by Dr. Gilles Montalescot, from the Hopital Pitie-Salpetriere in Paris, collected data on 259 patients aged 45 and younger who suffered a first heart attack and were given Plavix.

Among these patients, 28 percent carried a gene variation called CYP2C19*2. This variation is common among the western population and even more common in Asia, the researchers noted.

During an average of a year of follow-up, patients with the gene variation were more than three-and-a-half times more likely to die, have another heart attack or require additional cardiac treatment compared to those without the variation, the researchers found.

In addition, patients with CYP2C19*2 were six times more likely to have a blockage in a stent they had received after a heart attack.

Moreover, the variation continued to cause heart problems up to eight years after treatment with Plavix. In fact, patients with the variation were four times more likely to suffer additional heart problems after receiving the blood thinner.

So, what can be done to minimize the risk? "Checking people's genetic make-up after a heart attack is probably not necessary, since it may be better to do a different blood test to see if they have had a good anti-clotting response to clopidogrel," Storey said. He added that "new treatments that work more reliably than clopidogrel should hopefully be available within the next year or so."

Dr. Gregg C. Fonarow, a professor of cardiology at the University of California, Los Angeles, noted that treatment with Plavix in combination with aspirin does greatly reduce the risk of cardiovascular events in patients after an acute coronary event, or in patients undergoing coronary stent placement.

"However, it is well recognized there is variable response to clopidogrel, and some patients have thrombotic events, despite treatment with aspirin and clopidogrel," Fonarow said. "If these findings can be confirmed in additional studies, genetic testing may be useful in personalizing the choice and dosing of anti-platelet therapy in cardiovascular patients," he said.

Two other recent studies also found problems with Plavix in some patients.

In one study of 259 people treated with Plavix, published in the Aug. 12 issue of the Journal of the American College of Cardiology, researchers found that patients who smoked had significantly less clot formation than nonsmokers.

In a second study, published in the Oct. 28 online edition of the Journal of the American College of Cardiology, Austrian researchers found that calcium channel blockers drugs, widely prescribed to lower blood pressure, might reduce the Plavix' anti-clotting effects.

More information

For more on Plavix, visit the U.S. National Library of Medicine.

SOURCES: Robert F Storey, M.D., Cardiovascular Research Unit, University of Sheffield School of Medicine, U.K.; Gregg C. Fonarow, M.D., professor, cardiology, University of California, Los Angeles; Dec. 23, 2008, online edition, The Lancet

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