St. Louis, Feb. 8, 2005 -- A new study has shown a stroke-prevention drug designed to be an improvement over prior treatments is less cost-effective for most patients than warfarin, the blood thinner with a 50-year history of helping prevent blood clots and strokes. The study, conducted by researchers at Washington University School of Medicine in St. Louis found, however, that the new drug would be cost-effective for those atrial fibrillation patients whose risk of bleeding is high.
The findings are reported in the February 9 issue of the Journal of the American Medical Association.
In patients with atrial fibrillation, the upper part of the heart often quivers instead of beating, so blood pools and clots in the upper chambers. The blood clots tend to be large and can travel to the brain causing massive strokes.
AstraZeneca, the company that developed Exanta, had submitted a New Drug Application to the Food and Drug Administration for approval of the drug as an agent to prevent strokes in patients with atrial fibrillation as well as to prevent blood clots in other conditions. The drug was intended as an alternative to warfarin.
In October 2004, the FDA denied Exanta approval. The agency noted that Exanta carried a small risk of liver damage and cited insufficient evidence that it was as effective as warfarin for preventing strokes.
"Warfarin is extremely effective," says lead author Brian F. Gage, M.D., associate professor of medicine. "It lowers the risk of stroke by 65 percent. Unfortunately, patients have different sensitivities to warfarin, so it's difficult to adjust the dose, especially when initiating the drug. While they're on warfarin, patients' blood clotting has to be monitored often, and patients find that inconvenient. Warfarin also interacts with various foods and other drugs. Moreover, it doubles the risk of hemorrhage."
Before Exanta, the alternative for patients unable to tolerate warfarin was aspirin, which is not nearly as good as warfarin at preventing blood clots and strokes.
"Physicians would like to have a drug that's as effective as warfarin but doesn't require monitoring and is less likely to cause bleeding," Gage says. "That's why there was so much interest in Exanta--it reduces the risk of major hemorrhage by 26 percent and doesn't have warfarin's interactions or dosing problems."
The current study was undertaken to provide physicians with a rational way to choose among the three potential therapies. "Since each drug has its own drawbacks, trying to compare them was like comparing apples and oranges," Gage says. "We needed a common currency to make the comparison, so we accounted for quality of life factors and analyzed the way each drug affected quality-adjusted survival."
Gage and Washington University medical student Cara O'Brien compiled data from patients with atrial fibrillation and from the doctors that treated them, adjusting their ranking of each drug based on quality of life measures. They quantified the risk for adverse health conditions such as mild, moderate or severe stroke and looked at other factors that affect quality of life such as the need for multiple tests and ease of taking the medication.
O'Brien and Gage found that warfarin and Exanta were equivalent for preventing strokes and both were better than aspirin. The difference in quality of life measures among the three drugs was small. However, because of its higher price, Exanta was not cost-effective for most patients: the small gain in quality of life did not make up for the higher price in patients at low risk of bleeding.
On the other hand, the study showed that in patients with a high risk of bleeding as well as a significant risk of stroke, Exanta could increase quality of life and thereby increase its cost-effectiveness to a level that is acceptable by current U.S. health-care standards.
"We have a lot of octogenarians with atrial fibrillation and a high risk of bleeding, for example, because they tend to fall, have kidney disease or are taking anti-inflammatory medicine," Gage says. "In fact, close to a million Americans with atrial fibrillation are at relatively high risk for hemorrhage. For many of these people, Exanta would be cost-effective."
Exanta has been approved for use in about ten European countries, and observers believe AstraZeneca may soon appeal the FDA's original ruling and again seek approval for the drug in the U.S.
O'Brien CL, Gage BF. Costs and effectiveness of ximlelagatran for stroke prophylaxis in chronic atrial fibrillation. JAMA 2005 Feb 9;293(6):699-706.
Funding from the Agency for Healthcare Research and Quality and the Aetna Quality Care Research Fund supported this research.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
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