Heart medicine study to incorporate genetics
Personalized medicine, the tailored treatments that a few patients get based on their own DNA, is finally headed for the masses: the many heart patients at risk of deadly blood clots.
At least 2 million Americans with an abnormal, clot-triggering heart rhythm take the pill warfarin, also sold as Coumadin.
Getting too little can lead to a stroke, and too much can cause life-threatening bleeding. To find the right dose for each patient, doctors use trial and error -- and the errors lead to tens of thousands of hospitalizations and deaths every year.
Starting this month, about 1,000 patients who have a condition known as atrial fibrillation will take part in a project that will match their Coumadin dose to their specific genetic needs.
This genetic fingerprinting should single out the many people whose bodies break down warfarin more quickly or slowly than normal. Then their doctors can adjust their dosage to prevent dangerous complications.
“Twenty to 30% of people are either very fast or very slow” to metabolize many drugs but don’t know it, said Dr. Robert Epstein, chief medical officer at prescription benefit manager Medco Health Solutions of Franklin Lakes, N.J., which is collaborating in the effort with the Mayo Clinic.
Meanwhile, the federal government and researchers at Harvard University and elsewhere have begun or are planning similar studies.
Epstein and other experts say the warfarin projects make up the first broad use of personalized medicine, or targeted therapy, in which a person’s genetic makeup is used to pick the best medicine or dose. This approach essentially adjusts for differences in body chemistry that explain why one pain reliever or allergy pill works for you but not for your mom.
“It’s a big deal,” said Edward Abrahams of the Personalized Medicine Coalition, which includes industry, government and patient advocacy groups as well as insurers and research centers. “Warfarin is a very widely used drug, it’s been around for 50 years and it has all these adverse events associated with it.”
If the warfarin studies are successful, patients will start demanding personalized medicine, he predicted. Insurers will too, if the Medco study proves it saves money and protects patients.
That’s fairly likely, given Medco data showing that if patients have their warfarin dose changed more than once -- meaning doctors didn’t get it right the first two tries -- their risk of being hospitalized for complications jumps from 20% to 31%.
Epstein said he had hit “a home run” with his pitch to get employers and insurance companies sponsoring the prescription plans to join the study.
“Everyone we’ve talked to unanimously was in,” said Epstein, who expects the reduction in medical costs will be triple the test price of a few hundred dollars per patient.
He said a couple dozen companies already were developing commercial tests for variations in the two genes crucial in warfarin dosing, the ones in the new studies. But sales have been slow for the only government-approved testing device, Roche’s Amplichip, which covers numerous gene variations.
A November report by the American Enterprise Institute-Brookings Joint Center predicts that using genetic information to prescribe warfarin would save an estimated $1.1 billion in U.S. healthcare spending each year and prevent about 17,000 strokes and 85,000 serious bleeding incidents.
Bleeding complications alone kill about 8,000 people a year and are the No. 2 reason for medication-related ER visits, said Dr. Elizabeth Nabel, director of the National Heart, Lung, and Blood Institute. Still, warfarin is far better at preventing clots than aspirin or drugs like Plavix, which only affect part of the clotting system, she said.
But patients on warfarin must have blood drawn and tested repeatedly to see if it clots too quickly or too slowly, initially every week or more often.
“Most hospitals have a warfarin clinic, where people come in for adjustments,” she said.
So, along with the Food and Drug Administration, her institute plans one or two large studies on personalizing warfarin dosing. The FDA also is poised to alter the package insert for warfarin to note that gene variations in some patients mean they need a lower dose than normal.
Meanwhile, five Harvard Medical School teaching hospitals just began a study including 500 warfarin patients to try to boost the percentage getting the optimal dose. About 60% do now, said Dr. Samuel Goldhaber, a Harvard cardiologist.
And in the one-year Medco project, DNA from more than 1,000 patients’ blood samples will be shipped to the Mayo Clinic, which will do the genetic testing and send the results directly to the patient’s doctor. Medco, which manages prescription benefits for one in five Americans, plans to use the results to speed up adoption of the strategy, according to Epstein.
The studies will produce different but complementary information that can be pooled for a total picture, Goldhaber said.
Dr. Franklyn Prendergast, director of Mayo’s Center for Individualized Medicine, cautioned against assuming the results will be positive, because blood-clotting is a complicated process.
