A new, easier-to-use blood thinner pill offers the first potential alternative in 50 years to warfarin, the standard treatment given to millions of people to prevent blood clots.
The new drug has been tested in 17,000 patients for a number of uses and has shown to work as well as or, in some cases, better than warfarin at preventing dangerous blood clots. It acts more quickly and does not require the frequent blood testing of warfarin, also known as Coumadin.
In Thursday's New England Journal of Medicine, researchers report on two of the latest tests of the drug, Exanta. The studies showed it reduced the risk of blood clots by one-quarter after knee replacement surgery, and substantially cut the long-term risk of another clot developing in patients who had a blood clot in a leg or lung.
The drug maker, AstraZeneca, which paid for the studies, has filed for approval of Exanta in Europe and expects to apply for U.S. approval this year.
"I think in most cases it will replace warfarin because it is much easier and seems safer also," said Dr. Sam Schulman, who is at the Karolinska Hospital in Stockholm, Sweden, and led the long-term study of Exanta. "It will take some time, but I think that gradually patients will be switched."
Warfarin, originally developed as a rat poison, was first used as a blood thinner in the 1950s. It is still the only oral blood thinner available to protect against clots that can block blood vessels. It is widely prescribed after strokes, heart attacks and orthopedic surgery and is also given to prevent recurring clots in the legs or lungs.
But warfarin, which takes time to kick in, interacts with other drugs and foods containing vitamin K. It requires regular blood tests to adjust the dose. Doctors are wary of using it for more than a few months because of the risk of bleeding.
Exanta, also known as ximelagatran, works by targeting one coagulation factor; warfarin affects many. Exanta acts faster and does not have the monitoring or diet drawbacks.
"Everyone has Coumadin patients who aren't doing very well, so they'll probably try this," said Dr. Charles W. Francis who led the knee-replacement study at the University of Rochester Medical Center. "And if the experience is positive and patients do well, they'll use more and more of it."
The cost of Exanta has not been determined yet, according to AstraZeneca spokesman Gary Bruell. While warfarin itself is cheap - $1 or less a day - the required lab tests cost much more.
The Swedish study of 1,223 patients in 18 countries tested Exanta for the prevention of recurrent clots in people who had a leg or lung clot. They entered the study after getting warfarin for six months. For the next 18 months they got Exanta or a dummy pill.
Recurrent clots were found in 12 patients in the Exanta group and 71 in the comparison group, a reduction of 84 percent. Major bleeding was low in both groups. Six patients died in the Exanta group and seven in the comparison, including three of suffered fatal lung clots.
In about 6 percent of the Exanta group, there was an unexplained increase in liver enzymes, which has been seen in other studies of the drug. Schulman said levels increased in the first four months and then returned to normal without any apparent damage to liver function.
Dr. Sandor S. Shapiro, who wrote an accompanying editorial in the journal, said the liver problem is worrisome and needs to be followed.
"What's going to happen to those liver functions when people are on it for three, or four or five years? Is it possible that something will pop up again?" said Shapiro of Jefferson Medical College in Philadelphia.
The second study examined whether a higher dose of Exanta would be more effective in preventing blood clots after knee replacement surgery. About 2,300 patients in five countries received either one of two doses of Exanta or warfarin for up to 12 days after surgery.
About 20 percent developed clots in the high-dose group; 25 percent in the lower-dose group; and 28 percent for warfarin. There was no significant difference in bleeding. In a third study in the journal, researchers reported that a daily injection of the blood thinner Arixtra works as well as standard intravenous heparin in treating blood clots in the lung. Arixtra, also known as fondaparinux, does not require monitoring like heparin, and that can shorten hospital stays. The manufacture-sponsored study involved 2,213 patients. Arixtra is approved for use after hip and knee surgery.
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New England Journal: www.nejm.org