Studies Suggest Better Approaches To Staying Clot-Free

Research suggests that doctors could be guided better by genetic testing. People with abnormal heartbeats are often prescribed blood thinners to protect against stroke and heart attacks.

The researchers found that Warfarin is an extremely popular drug, however, it can also be difficult to take. According to the American Heart Association, patients who take too much Warfarin can experience unusual bleeding and possibly vomiting.

But doctors who used genetic testing to guide patients' warfarin doses were better able to quickly reach and consistently remain within the drug's therapeutic "sweet spot," according to the study. The study was presented at Tuesday's AHA annual meeting in Dallas and published online in the New England Journal of Medicine, November 19, 2009.

Barbara Howard, senior scientist at MedStar Health Research Institute Hyattsville Md., stated that bleeding-thinning therapy is both difficult and can have a variety of side effects. It is crucial to know the right dose, which is where genetic testing may be a useful tool. Howard, who is also a Georgetown University Hospital professor, wasn't involved in the new research.

The study involved about 450 patients, approximately half of whom were randomly assigned to receive a genetic test that would guide their warfarin dose, said the study's lead author, Munir Pirmohamed, chairman of pharmacogenetics at the University of Liverpool, in England.

Pirmohamed stated that Warfarin was 60 years old. Dwight D. Eisenhower was the first person to be given this drug. He said that despite the fact that this drug is old, its dosing guidelines have not changed.

About three-quarters of the patients in the study suffered from atrial fibrillation, a heart rhythm disorder that increases a person's risk of heart attack and stroke by allowing blood to pool in one of the heart's chambers. Deep vein thrombosis was the condition that causes blood to clot in the veins, increasing risk of stroke and heart attack in patients.

Pirmohamed stated that doctors used two genes related to the blood-clotting process in order to determine how much medication someone would get.

A genetically-guided warfarin dosage kept patients within the therapeutic sweet spot during 67 percent of the three-month treatment. This compares with 60% for those who were not treated with genetic guidance.

Pirmohamed explained that genetic dosing patients reached the sweet spot around 28 percent quicker. A stable, long-term dosage was also possible 25 percent quicker. They also required 9 percent less dose adjustments.

A limited genetic test was used by the researchers, and it costs approximately $67.

According to a U.S. expert, genetic testing could prove more valuable in future drug dosage determinations due to falling costs.

An inexpensive test which can determine a person's whole genetic code costs around $1,000, down from $80,000 just a few decades ago. This is according to Dr. Joseph Loscalzo who chairs the department of medicine and is physician-in-chief at Brigham and Women's Hospital. Loscalzo is also editor-in chief of Circulation. He said that he believes such a test will one day be as low as $100.

Howard, a MedStar representative said that a patient would need only one genetic test in order to guide their treatment. After all, genetics do not change.

However, the picture of these tests is still hazy. A related study, led by Dr. Stephen Kimmel, of the University of Pennsylvania Perelman School of Medicine, was presented Tuesday at the AHA meeting. The study of nearly 1,000 patients found no significant difference between those whose warfarin dose was based on genetic testing and those with doses set using current guidelines.

In that study, both groups of patients were in the therapeutic sweet spot about 45 percent of the time.

The difference between the two studies might be the other factors beyond genetics that can determine warfarin dosing, said Dr. Patrick Ellinor, a cardiologist at the Massachusetts General Hospital Heart Center.

These factors may include age, gender, race, and whether the patient smokes or has other health issues. Ellinor is also an associate professor at Harvard Medical School.

Another study suggested a potential substitute for warfarin. The study found that the medication edoxaban does just as good a job preventing stroke and heart attack but with significantly lower risk of bleeding.

The edoxaban study involved more than 21,000 atrial fibrillation patients at nearly 1,400 hospitals in 46 countries.

Edoxaban performed just as well as warfarin in preventing strokes, according to the study, which was published recently in the New England Journal of Medicine and presented at the AHA meeting.

Major bleeding rates were 20 percent higher in patients who received a high dose of Edoxaban than they were for patients receiving a lower dose. They were 53 percent less among patients who took a lower dose.

The high dose of Edoxaban had a 14% reduction in stroke or heart attacks compared to the warfarin. While the low dose produced a 15% reduction.

"We know this drug is safer than warfarin, particularly at a low dose," said the study's lead author, Dr. Robert Giugliano, a researcher and physician at Brigham and Women's Hospital.