After his heart attack last December, Rabbi Daniel Siegel had two stents implanted in his blocked coronary arteries, and he started on a course of drugs to prevent further clots from forming.
It was Siegel’s second heart attack in a little over five years, and each time his doctors prescribed him the same anti-clotting medicine: Plavix, known generically as clopidogrel.
Yet Siegel’s doctors did not do one thing that drug regulators and scientific experts strongly advocate. They did not also order a genetic test that could have predicted whether Siegel would actually benefit from Plavix’s blood-thinning action.
“No one has ever talked about that,” says Siegel, a resident of Hornby Island, British Columbia, and the director of spiritual resources for ALEPH: Alliance for Jewish Renewal, an international organization based in Philadelphia.
Siegel’s Canadian doctors are not alone. On the U.S. side of the border, only around one in every 200 physicians actually considers DNA data when prescribing Plavix, according to research from Medco Health Solutions, a healthcare company headquartered in Franklin Lakes, N.J. This low uptake of genetic testing remains despite the fact that in 2010 the Food and Drug Administration added a “black box” warning to Plavix’s prescribing information that noted the link between certain genetic traits and reduced drug response. Such “poor metabolizers,” the FDA said, “may remain at risk for heart attack, stroke, and cardiovascular death.”
The FDA came to that conclusion after considering the results of numerous clinical trials involving thousands of heart patients, which collectively showed that having a reduced-function gene variant dramatically increases the risk of stent thrombosis and other complications. Yet, despite the wealth of medical data, adoption rates of the tests remain low.
“If you look in the literature, the evidence base is compelling,” says Dr. Alan Shuldiner, associate dean for personalized and genomic medicine at the University of Maryland School of Medicine. “The challenge really has been to take these discoveries and move them into the clinic.”
The gene underlying Plavix metabolism is known as CYP2C19. This gene encodes a liver enzyme that helps convert Plavix into its active form to have a full effect. Around 20% of North American Caucasians harbor genetic mutations in this gene that render them less capable of metabolizing Plavix. For these people, doctors often prescribe other antiplatelet agents, such as prasugrel, that don’t rely on CYP2C19 status yet cost more and have higher rates of complications.