The Food and Drug Administration said that Sanofi-Aventis and Bristol-Myers Squibb Co. have agreed to conduct studies to better characterize the effectiveness of clopidogrel (Plavix) in patients with certain genetic factors. The two manufacturers also said they will lead clinical trials to assess what effects other therapies, such as proton pump inhibitors, might have on clopidogrel's efficacy.
Several recent studies have raised doubts about the anticlotting agent's effectiveness in patients with certain genetic profiles. “The FDA is aware of published reports that clopidogrel is less effective in some patients than it is in others,” the agency said.
According to the FDA's posting on its Web site, the two drug makers have agreed to complete the studies within a certain time frame. However, “it could take several months to complete the studies and analyze the results.”
In the meantime, physicians should continue to prescribe clopidogrel, said the agency. Patients should not stop taking the drug but should talk with their physicians if they are currently taking a PPI or considering starting on one, including the over-the-counter omeprazole (Prilosec).
The agency cited six published reports looking at the effects of PPIs or certain polymorphisms on clopidogrel. Most were published in 2008. Missing from the FDA's reference list were three studies published at the end of December and in early January.
One found that acute myocardial infarction patients with a CYP2C19 loss-of-function allele who took clopidogrel had a higher rate of cardiovascular events (N. Engl. J. Med. 2009;360:363-75). Another found that patients with acute coronary syndromes who had the same polymorphism had lower levels of the active clopidogrel metabolite and thus a higher rate of cardiovascular events (N. Eng. J. Med. 2009;360:354-62). A third study found that, in patients under age 45 years with the same polymorphism, clopidogrel was less effective (Lancet 2009;373:309-17).