The FDA says certain patients with a genetic variation cannot metabolize the drug, putting them at increased risk for heart attack and stroke.
For Plavix to work, enzymes in the liver, particularly CYP2C19, must convert (metabolize) the drug to its active form, the FDA said on its Web site. In patients who are poor metabolizers of the drug, Plavix has less effect on platelets, and therefore less ability to prevent heart attack, stroke, and cardiovascular death.
It is estimated that 2 to 14 percent of the population are poor metabolizers.
Patients can determine if they don't respond to Plavix by taking a genetic test to identify differences in CYP2C19 function. The FDA recommends non-responding patients take other blood thinners, such as aspirin.
The new Plavix warning will appear within a black box, the FDA's most severe warning.
Plavix is marketed by Sanofi-Aventis and Bristol-Myers Squibb. With global sales of $8.6 billion in 2008, it was the world's second-best selling drug behind Pfizer's cholesterol drug Lipitor.
The Associated Press contributed to this report.