Genetic Testing Cited for Warfarin

[Susan BAV]

I saw this on the ABC evening news tonight and found it very interesting. I thought some of you would also:

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Genetic Testing Cited for Blood Thinner - FDA Notes Role Genetic Testing Can Play in Safer Use of Blood Thinner
By ANDREW BRIDGES - The Associated Press - WASHINGTON

"Federal health officials are stopping short of recommending genetic tests for patients on the blood-thinner warfarin, even though they have said such screenings could prevent thousands of complications each year.

Warfarin, sold under the brand name Coumadin and in generic forms, on Thursday became the first widely used drug to include genetic testing information on its label. The information can help doctors determine how best to prescribe the drug.

"This means personalized medicine is no longer an abstract concept but has moved into the mainstream," the Food and Drug Administration's clinical pharmacology chief, Larry Lesko, said in announcing the label change.

The updated label for warfarin suggests that lower doses may be best for patients with variations in two specific genes. One produces an enzyme that helps the body metabolize warfarin and other medicines; the second produces the blood-clotting protein that warfarin blocks.

The FDA has not changed its dosing recommendations for the drug, and tailoring the proper dosage remains largely a matter of trial and error.

A patient's age, weight, diet and other prescription drug use all play a role in determining a proper dose. Patients taking too much warfarin can bleed to death. If people take too little of the drug, it can fail to protect them from deadly blood clots and stroke.

Genetic testing can reveal which patients may require less of the drug and lead doctors to recommend doses closer to the lower end of the scale, FDA officials said.

Rebecca Burkholder, vice president of health policy for the National Consumers League, said the FDA's action was a good first step. But she said that once patients are on the drug, they still must have regular blood tests to see if it is working properly.

Changes in diet, for example, can lead to further dosing tweaks something even genetic testing will not eliminate.

A survey done by the group last year found too few patients on warfarin understood some basic steps they were supposed to take to avoid complications.

FDA economists estimate the genetic testing could prevent 85,000 "serious bleeding events" and 17,000 strokes a year, according to a November 2006 study posted to the Web site of the American Enterprise Institute. The savings to the health care system could be $1.1 billion a year, though some people question that. The genetic tests can cost $125 to $500. About 2 million people start taking the drug each year.

Warfarin sends more than 43,000 people to the emergency room each year, the FDA economists said. That total is more than for any other drug except insulin, which diabetics use.

About one in three warfarin patients metabolizes, or clears, the drug differently than anticipated. Variations on two genes explain some of those differences.

One gene, CYP2C9, produces an enzyme that helps the body metabolize a variety of medicines, including warfarin. People whose bodies process warfarin more slowly would need a smaller dose.

A second gene, VKORC1, produces the blood-clotting protein that warfarin blocks. A patient's body that churns out less of that protein also would need less warfarin.

FDA officials said they would hold off on recommending or requiring the tests for those genetic variants until the completion of studies to show whether doing so would actually benefit patients. An outside expert said doing otherwise would have been premature.

"What we need to do is find out whether genetic testing improves outcomes," said Dr. Brian Gage of Washington University in St. Louis.

The FDA was to have begun that type of study in November but scrapped it for lack of money. The National Institutes of Health has since announced plans for such a trial.

Bristol-Myers Squibb Co. makes Coumadin. A message left with a spokesman was not immediately returned. A half-dozen other companies make generic versions of the drug."

 

[Ross]

What a tremdous waste of money. Why can't they spend the money to educate Doctors and Coumadin managers on proper dosing instead of looking for alternative ways to dose? Bottom line, your INR is the guide to dosing. Until managers know how to dose for a proper INR, nothing is going to matter.

 

[Cooker]

The medical community has been after me for years to consent to genetic testing. Personally I don't understand their interest.

 

[Karlynn]

The medical community has been after me for years to consent to genetic testing. Personally I don't understand their interest.

Cooker - there are just some things that are better left unknown.

The information is interesting. Thanks Susan. Along the same lines as Ross, my first thought when I read Safer Use of Blood Thinner was that most unsafe aspect of using warfarin was the lack of interest in the medical community to manage it based on 2007 standards and not 1990 standards.

Coumadin is not an unsafe medication when managed properly. There are many other more common medications that are taken without a second thought that are riskier than Coumadin. For me, the risk isn't taking properly managed Coumadin, it's the risk associated with clots forming on my valve should I need to stop taking it.

Yes, there are increased risks with head injury and other bleeds associated with accidents. However, people who take anti-inflamatories regularly for pain should also be concerned about bleeding incidents.

My brother-in-law, who teaches pharmacology, told me a few years ago that Tylenol should really be a prescription because of the things they are now learning about it's effects on the liver and other organs when taken regularly. But its viewed by most of the public as being the safest of pain medications.

I see Coumadin as having the same problem as the once gawky 12 year-old had in shaking the nerd label once they'd outgrown that stage and turned into a handsome young person. Some people still view him or her as that awkward 12 year-old.

 

[Susan BAV]

I'm glad you found it interesting also.

I'm glad you found it interesting also.

The news anchor, Charlie Gibbons, briefly interviewed a doctor too and the impression I got was that this might eventually be a good test for people who were just beginning anticoagulation therapy; but people who were already stable on it probably wouldn't find it necessary to do the testing. It seemed to me the point they were making on the television news was that the goal was to find how to help people become stable more quickly upon beginning warfarin.

I was only on Coumadin for three months post-op, but my brief experience wasn't very successful--I might have been in range once--even though I tried to be educated about it and read everything I could about it and tried to completely inform myself about it and tested as directed and tried to do everything correctly. I assumed it was a bit of mismanagement to some degree because there was some conflict between the hospital and two different doctors' offices; but instead, perhaps, a more finely-tuned genetic test would place the error with my body's processing of the medication.

 

[Ross]

Susan I guarantee you, if the person managing you or your managing yourself, knows what their doing, there is no need for expensive genetic testing on top of something that has to be done anyhow. The KEY IS EDUCATED MANAGEMENT. We know all too well that this is a steady, ongoing problem throughout the U.S. There are too many bad managers, rumors and other things, that keep warfarin/Coumadin dangerous. Eliminate the bad management, rumors and other things, and you'll effectively eliminate the danger.

 

[Karlynn]

I guess my hope would be that if doctors started ascribing to this genetic test, they would also make the effort to update their overall knowledge. Or that, in order to use this genetic test, practitioners must go through a course on warfarin management, and pass a test, before they are allowed to use the genetic testing. They should be required to show current understanding of management protocol.

What wouldn't work is a genetic test that helps set a dose, but a poorly educated warfarin manager that still gets their knickers in a bunch over mildly changing INR's. I could see someone thinking "This dose should be working, according to the test - what's wrong with what the patient is doing?" and start trying to ferret out every possible reason from green Jell-o to too much salad and try and get the patient to adjust rather than adjust the dosage.

This genetic test can be a good thing, if it's coupled with overall management education. It won't do any good to provide a doctor or facility with a test to start a correct dose, only to have them mess up the patient because they are still adhering to ancient practices.

 

[Ross]

Here is where I have a problem with it. We have Doctors that start their patients with loading doses of 10 to 15mg and have them test in 3 days. Well guess what? These folks are going to show falsely high, so they back off the dose and bring them way too low, then hit the gas with another loading dose and the teeter totter is started. It would be wiser, in my opinion, to start everyone off at 5mg per day for at least 4 days before testing, then continue or bump from there. Whether your a slow of fast metabolizer is of no concern if dosing is approached properly.