Patients with a particular gene variation are two times more likely to have a heart attack or stroke while taking the anticlotting drug Plavix than those without the variation, according to a study to be published Wednesday in the Journal of the American Medical Association.

The study confirms earlier research suggesting that the 30% of the population who has the gene variation responds less effectively to Plavix, a Bristol-Myers Squibb Co. (BMY) and Sanofi Aventis SA (SNY) drug with more than $8 billion in annual sales.

Plavix, a blood-thinning drug used to prevent blood clots, is the second top-selling drug globally after Pfizer Inc.'s (PFE) Lipitor. Plavix is commonly prescribed to patients with artery-opening stents or those who have had a heart attack or stroke.

Studies published last year suggested a gene may prevent Plavix from working effectively in certain patients, putting them at higher risk for another heart attack or stroke. Coupled with other research showing Plavix may not work effectively with common heartburn drugs, the U.S. Food and Drug Administration got Sanofi and Bristol to update the drug's label with information about how genetics can interfere with the medicine.

Sanofi and Bristol representatives weren't immediately available to comment.

The JAMA study to be published Wednesday, which was financed by the National Institutes of Health, tested Plavix in 429 healthy Amish people and 227 other patients who underwent artery-opening procedures. Patients with the gene variant were twice as likely to have another heart attack or die when compared with those without the variation.

Although it is unclear why people with the gene variation don't respond well to Plavix, the gene seems to stop an enzyme from working that is needed to activate Plavix in a patient's body.

Dr. Paul Gurbel, an author of the JAMA study, said the research goes beyond the earlier studies to show a more direct connection between the gene variant and Plavix's effectiveness. Gurbel is also a cardiologist at Sinai Hospital in Baltimore and first reported, in 2003, that the gene variant might interfere with Plavix's effectiveness. He said more research is needed before doctors begin genetically screening patients to determine if Plavix is right for them.

"Until we have larger studies we can't leap that far," Gurbel said. Gurbel has received grant support from Sanofi and has consulted with AstraZeneca Plc (AZN) on a potential competitor to Plavix, Brilinta. Brilinta isn't approved in the U.S., though results of a large study are expected to be announced this weekend in Spain.

The study notes that a variety of factors, including a person's weight and health, may affect how well they respond to Plavix. An editorial that will accompany the study says combined with prior research, the likelihood that the gene variation is preventing Plavix from working properly is "high."

Bristol and Sanofi have agreed to work with the FDA to conduct studies to better understand how Plavix works in patients with certain genetic factors, and with other drugs.

-By Jared A. Favole, Dow Jones Newswires; 202-862-9207; jared.favole@dowjones.com