TUESDAY, Feb. 8, 2005 (HealthDay News) -- Two studies sharpen the debate about the potential benefits and risks of a new anti-clotting drug.
The drug, sold as Exanta (ximelagatran), is a potential replacement for Coumadin (warfarin), which can, among other things, prevent stroke in people with the heartbeat abnormality known as atrial fibrillation. While Coumadin is widely prescribed it is also notoriously difficult to manage, requires frequent blood tests to monitor clotting levels, and has adverse reactions with a number of other drugs.
Exanta has none of those problems. However, the U.S. Food and Drug Administration (FDA) has not approved its use in this country, and several European countries have approved the drug only for limited purposes, because some people who take it experience increases in levels of an enzyme associated with liver damage.
The studies in the Feb. 9 issue of the Journal of the American Medical Association try to tackle this issue; one looked at people with atrial fibrillation and the other reported on those with deep vein thrombosis.
The first compared Exanta with Coumadin in 3,922 people with atrial fibrillation and other risk factors for stroke. The American researchers found the incidence of stroke was slightly higher for those who took Exanta -- 1.6 percent per year, compared to 1.2 percent for those who took Coumadin. There was no difference in the incidence of major bleeding episodes, but the overall incidence of bleeding episodes was about a third lower for those who took Exanta.
However, levels of enzymes indicating possible liver damage rose to greater than three times the normal limit in 6 percent of patients taking Exanta, usually within six months, although those levels typically declined whether or not Exanta treatment continued.
The second study compared Coumadin against Exanta in nearly 5,000 Europeans with deep vein thrombosis -- blood clots in the legs, arms or pelvis. The risk of recurring blood clots was virtually the same in both groups -- 2.1 percent for Exanta and 2 percent for Coumadin. The risk of major bleeding was much lower for the Exanta group -- 1.3 percent vs. 2.2 percent for the Coumadin group. Liver enzyme levels rose to greater than three times normal in 9.6 percent of those taking Exanta.
Dr. Jonathan L. Halperin, a professor of medicine at the Mount Sinai School of Medicine in New York City and leader of the U.S. study, said the findings indicate that many people with atrial fibrillation could benefit from Exanta -- but with significant conditions attached.
"We need some tool to allow us to prescreen patients for liver problems," Halperin said. "We also need better methods to monitor patients who take this medication."
Because doctors often hesitate to prescribe Coumadin because of difficulties it presents, approval of Exanta could help many patients with atrial fibrillation, Halperin said. "We have to trade off the risk of stroke against liver abnormalities," he said.
Further clinical trials are unlikely to settle the issue because Exanta has already been tested in trials including more than 18,000 people, said Dr. Victor Gurewich, a professor of medicine at Harvard Medical School and the author of an accompanying editorial. Like Halperin, he said he favored FDA approval, but with strict controls and monitoring.
"Diligent post-marketing surveillance is essential to monitor use and to determine the risk associated with this agent," he wrote.
About 1.3 million Americans suffer from atrial fibrillation, with that number growing as the population ages. The incidence of stroke among these patients is two percent a year, Gurewich said, and only half of them now get Coumadin because of the difficulty involved in prescribing the drug.
A twofold strategy is recommended by Dr. Brian F. Gage, an associate professor of medicine at Washington University School of Medicine. He co-authored an analysis in the same issue of the journal.
That analysis shows that in terms of dollars and cents, substituting Exanta for Coumadin would not be cost-effective for people with atrial fibrillation who have a low risk of bleeding complications, Gage said. But it could be effective for patients who now are given aspirin to prevent clots because they have a high risk of bleeding complications if given Coumadin.
"I would like to see a randomized trial of ximelagatran vs. aspirin in patients with atrial fibrillation who have one or more contraindications for use of warfarin," Gage said. "Compared to aspirin, this would be a highly effective drug. We would follow these patients for a set length of time for safety and effectiveness. I suspect that in this patient population, ximelagatran would have substantial benefits."
In addition, drugmaker AstraZeneca -- which markets Exanta and financed the two studies -- should follow patients in any clinical trial who have elevated levels of liver enzymes to determine the exact risk of liver failure, he said.
More information
The risks and treatment of atrial fibrillation are described by the American Heart Association.
