* Variation makes Plavix less efficient
* Nearly a third of the population has it
* Findings could lead to screening tests

A common gene variation explains why many people are not helped by the widely prescribed blood thinner Plavix, U.S. researchers said on Tuesday in a study confirming earlier research and paving the way for tests to screen patients before they get the drug.

They said one version of the gene CYP2C19, carried by nearly a third of the general population, plays a major role in their response to Plavix or clopidogrel, an $8 billion a year drug made by Sanofi-Aventis (SASY.PA) and Bristol-Myers Squibb Co (BMY.N) to prevent heart attacks and strokes.

Those who had the variation and took Plavix after a procedure to open blocked heart arteries were 2.4 times more likely to die or have a heart attack or stroke than those who did not have the variant and took the drug.

The gene variation is a strong predictor of response to clopidogrel or Plavix, said Dr. Alan Shuldiner of the University of Maryland School of Medicine in Baltimore.

About 30 percent of Caucasians and blacks have this variation, Shuldiner said in a telephone interview. But it is much more common in Asians -- up to 60 percent of them have at least one copy of it.

Shuldiner, whose study appears in the Journal of the American Medical Association, said the mutated gene produces a deficient enzyme.

People with this variation do not convert Plavix from its inactive form to its active form, and therefore are less responsive to clopidogrel, he said.

HIGHER DOSAGE OR NEW DRUG

For the study, Shuldiner analyzed the genetic code of 429 healthy Amish people in Lancaster County, Pennsylvania. Volunteers took Plavix for seven days and then the team looked to see how their blood platelets responded. They also looked for common gene variants, and CYP2C19 turned up.

They tested their findings in a different study of 227 people undergoing treatment with a stent to prop open blocked heart arteries. Those who had the gene responded poorly to Plavix, and were twice as likely to have a heart attack or stroke in the year after their treatment.

Dr. Deepak Bhatt of the Veterans Affairs Boston Healthcare System and Brigham and Women's Hospital in Boston said in a commentary that the study supports earlier findings.

Right now up to a third of people who take Plavix do not respond to it, Shuldiner said. This discovery, I think, may ultimately lead to genetic testing that could be done on any individual who will be starting Plavix, he said.

People with the variation might need to take a higher dose, he said. Or they might be prescribed Eli Lilly and Co (LLY.N) and Daiichi Sankyo Co Ltd's (4568.T) newly approved blood thinner Effient, known generically as prasugrel, which Shuldiner said appears to work on people who fare poorly on Plavix.
Plavix loses its patent in 2011 and generic versions can be made. Shuldiner said he thinks ultimately genetic testing may help doctors choose between generic Plavix and the more costly branded drug Effient. (Editing by Maggie Fox and Xavier Briand)

Pennsylvania