Apixaban superior to warfarin for preventing stroke, reducing bleeding and saving lives

A large-scale trial finds that apixaban, a new anticoagulant drug, is superior to the standard drug warfarin for preventing stroke and systemic embolism in patients with atrial fibrillation. Moreover, apixaban results in substantially less bleeding and also results in lower mortality.

The results were presented by Duke University Medical Center researchers at the European Society of Cardiology in Paris, France, today, and published simultaneously online in the New England Journal of Medicine.

"These are important findings because they show that, when compared to warfarin, a very effective treatment to prevent stroke, apixaban resulted in an additional 21 percent relative reduction in stroke or systemic embolism," says Christopher B. Granger, M.D., the study's lead author and professor of medicine at Duke. "It also resulted in a 31 percent relative reduction in major bleeding, as well as an 11 percent relative reduction in overall mortality."

The improvement in stroke prevention was statistically significant with P=0.011, the lower rate of major bleeding at P<0.001, and the lower mortality at P=0.047. Hemorrhagic stroke was reduced by about 50%.

The randomized, double-blind clinical trial known as ARISTOTLE randomized 18,201 patients at 1034 clinical sites in 39 countries, giving them either 5 mg twice daily of apixaban or warfarin for an average of 1.8 years.

Apixaban has several major practical advantages over warfarin in addition to the therapeutic benefits, says John Alexander, M.D., a study co-author and Duke cardiologist. "It does not require monitoring and has few interactions with other medications or food. Apixaban was better tolerated than warfarin, with fewer discontinuations."

The benefits of reducing stroke and lower rates of bleeding were consistent across all major subgroups, and despite the heterogeneity that exists in the quality of warfarin use across the world, says Alexander.

The number of events prevented per 1,000 people, which indicate absolute risk reduction, was also impressive, says Alexander. Apixaban prevented 6 patients from having a stroke, 15 patients from having major bleeding, and 8 patients from dying. The major effect on stroke prevention was on hemorrhagic stroke. Apixaban prevented 4 patients from having hemorrhagic stroke and 2 patients from having an ischemic or uncertain type of stroke.

Atrial fibrillation is a common abnormal heart rhythm that affects more than 2.6 million Americans. It occurs when the heart's electrical activity becomes disorganized, resulting in an irregular heartbeat with ineffective contraction of the upper chambers of the heart. The potential for blood clots to form, and one's risk for stroke, increases as a result.

Warfarin is a vitamin K antagonist that is well documented for its ability to prevent blood clots. Previous studies indicate that long-term use of warfarin in patients with atrial fibrillation and other stroke risk factors can reduce stroke by up to 70 percent. But only about half of patients who could benefit from warfarin actually do. Patients on warfarin must have regular blood tests to monitor and adjust the dose and avoid certain foods and medications that interfere with warfarin's effect. Warfarin also increases bleeding rusj including including intracranial hemorrhage.