Stroke-prevention drug study compares therapies

A new study has shown the stroke-prevention drug Exanta, 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.

However, School of Medicine researchers did find that Exanta would be cost-effective for patients whose risk of bleeding is high.

The findings were reported in the Feb. 9 issue of the Journal of the American Medical Association.

Exanta was developed by AstraZeneca as an alternative to warfarin for preventing blood clots and strokes.

The Federal Drug Administration denied Exanta approval in October, noting that it carried a small risk of liver damage and citing insufficient evidence that the drug was as effective as warfarin for preventing strokes.

Warfarin is extremely effective, lowering the risk of stroke by 65 percent, explained senior author Brian F. Gage, M.D., associate professor of medicine.

“Unfortunately, while a patient is on warfarin, blood clotting has to be monitored often, and patients find that inconvenient,” Gage said. “Warfarin also doubles the risk of hemorrhage.”

Before Exanta, the alternative for patients unable to tolerate warfarin was aspirin, which is not nearly as effective in 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 said. “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 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 said. “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 University medical student Cara O’Brien quantified the risk for adverse health conditions, such as mild, moderate or severe stroke, and looked at other factors that affect quality, such as the need for multiple tests and ease of taking the medication.

The team 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. A 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 who have a high risk of bleeding and a significant risk of stroke, Exanta could increase quality of life and thereby increase its cost-effectiveness.

Exanta has been approved for use in about 10 European countries, and observers believe AstraZeneca may soon appeal the FDA’s original ruling and again seek approval in the United States.