Seeking a new blood thinner
For more than 50 years, warfarin has been used to prevent dangerous blood clots in people with a variety of medical conditions. But it’s not an easy drug to take. The levels circulating in the blood can change rapidly depending on other medications, food, activity and illness; and frequent blood tests are required to make sure the dosage is adequate. And the drug, which is also used as rat poison, can be dangerous in high doses.
A new medication, Exanta, promises the same benefits as warfarin, more commonly known as Coumadin, without some of the problems.
“We have a [long] track record in knowing what the side effects of warfarin are,” said Dr. Alan K. Jacobson, a cardiologist at Loma Linda Veterans Hospital and an investigator studying Exanta. Warfarin works through the liver, which is a very sensitive organ and affected by “pretty much anything,” he said.
“As a patient’s lifestyle changes, the drug absorption changes, and we end up doing lots of monitoring,” he said.
Jacobson estimates that only one-quarter of people on warfarin are managed as carefully as they should be.
Unlike warfarin, which boosts blood clotting proteins, Exanta interferes with a protein, called thrombin, that is needed in blood clot formation. It does not work through the liver, and most people respond to the same dose of the drug, without the need for adjustment and monitoring, Jacobson said.
In studies so far, Exanta worked as well as warfarin in preventing and treating blood clots. The drug, made by AstraZeneca, is in Phase III studies, which is usually the final stage before the manufacturer requests Food and Drug Administration approval. It is being tested in more than 20,000 patients worldwide for prevention of stroke in people with atrial fibrillation, for deep vein thrombosis and in people who have just had hip replacement surgery.
Most people seem to tolerate Exanta well, Jacobson said. However, researchers are still studying whether the medication might be harmful to people with kidney failure.
Because it’s an anticoagulant, Exanta does not resolve the risk of increased bleeding that such drugs pose. The thinning of the blood creates the potential for uncontrolled bleeding after an injury.
“People who bleed [easily] are still going to have a problem with this drug,” Jacobson said. “Elderly people who fall a lot, for example, may not be much safer taking Exanta than they are taking Coumadin.”
Anyone who is a candidate for oral anticoagulants, whether warfarin or Exanta, should first be examined to assess the risk of bleeding. “One of my concerns with Exanta is that physicians may skip that process” because they assume Exanta carries none of the same risks as warfarin, Jacobson said.
Even if Exanta is eventually approved for use in the United States, it will not replace warfarin, he said. Warfarin costs about 50 cents to $1 a day, and a new brand-name drug will probably cost much more.
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Preventive therapy
Anticoagulants are most commonly used by people at high risk for developing blood clots, such as people with a heart condition called atrial fibrillation.
More than 2 million people in the United States have atrial fibrillation, which is an irregular heartbeat. The condition leads to a high risk of stroke because blood doesn’t pump evenly through the heart’s chambers, leading to pooling and possible clotting. One European study showed that 18% of people who were hospitalized with their first stroke were found to have atrial fibrillation.
Although oral anticoagulants can reduce the risk of stroke from atrial fibrillation, doctors are sometimes reluctant to prescribe warfarin because of the difficulties in monitoring the drug. Thus, some atrial fibrillation patients do not receive preventive therapy for stroke, said Dr. Palle Petersen, a stroke expert in Denmark who has studied anticoagulants for stroke prevention.
