Genetic Medicine: Heart Patients on
Warfarin Will Get DNA Tests to
Determine Correct Dose
January 12, 2007 08:37
By LINDA A. JOHNSON
TRENTON, N.J. -- Personalized medicine, the tailored treatments that a
few patients now 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 faster or slower than normal, and their
doctors can immediately adjust their dosage to prevent dangerous
complications.
"Twenty to 30 percent 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, based in Rochester, Minn.
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 comprise 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 great 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 percent to 31 percent.
Epstein said he's 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 noted a couple dozen companies already are developing commercial
tests for variations in the two genes crucial in warfarin dosing, the
ones in the new studies. However, sales have been slow for the only
government-approved testing device, Roche's Amplichip, which covers
numerous gene variations.
A November 2006 report by the American Enterprise Institute-Brookings
Joint Center predicts using genetic information to prescribe warfarin
would save an estimated $1.1 billion in U.S. health care spending each
year, while preventing 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 fast or too slow, initially every week or more
often.
"Most hospitals have a warfarin clinic, where people come in for
adjustments," she noted.
So along with the Food and Drug Administration, her institute now is
planning 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. Only about 60 percent do now, said Dr. Samuel
Goldhaber, a Harvard cardiologist and professor.
At the Marshfield Clinic Research Foundation in Wisconsin, a new study
will compare results for 250 patients getting warfarin through standard
trial and error with 250 getting doses that are genetically based, said
Dr. Michael Caldwell, who started the personalized medicine program
there in 2000.
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 complete 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 very complicated process.
However, he noted that doctors are now able to use gene tests to find
the right treatments for patients with breast and lung cancer, leukemia
and a rare brain cancer.
Uses in other areas of medicine, such as psychiatry, are generally
limited to top academic medical centers, but likely will expand as
research proves its value and testing becomes cheaper.
Dr. Eric Braverman, director of integrated medicine at Cabrini Medical
Center in New York, said more research is needed to prove personalized
medicine improves care, but studies so far show promise in areas from
Alzheimer's to addiction and obesity. He predicted personalized
medicine will one day be used to forecast a child's potential future
health problems, such as heart disease, so that preventive diet and
lifestyle changes can be made early.
As Prendergast put it: "The potential is unbelievable for doing good."
___
On the Net:
Personalized Medicine Coalition:
http://www.personalizedmedicinecoalition.org
Medco Health Solutions:
http://www.medco.com
Atrial circulation information:
http://www.americanheart.org/present...ml?identifier9
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