Final data show experimental agent better than aspirin at preventing stroke

A new anti-clotting agent is vastly superior to aspirin at reducing stroke risk (1.6 percent per year versus 3.6 percent per year) in atrial fibrillation (AF) patients unable to take stronger drugs, according to final data reported today at the American Stroke Association's International Stroke Conference 2011. Researchers found the drug also works better in people with a history of stroke or a warning stroke.

Atrial fibrillation is a heartbeat abnormality that can cause blood clots which raise the risk of stroke, particularly in the elderly.

The AVERROES: Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Strokes trial is a randomized trial of 5,600 AF patients at moderate to high risk of stroke who were not willing or able to take oral vitamin-K antagonists like warfarin, a drug commonly prescribed to prevent blood clots in people with AF. They were treated at 520 medical centers worldwide. A May 2010 interim analysis found evidence that the investigational oral drug apixaban was so much more superior to aspirin that the researchers were advised to end the trial early, said Hans-Christoph Diener, M.D., professor and chairman, Department of Neurology and Stroke Center, University Hospital Essen, Essen, Germany.

In releasing the study's final results, he reported that apixaban was far superior to aspirin at preventing stroke or systemic embolism (blood clot) and was also very safe. The drug blocks factor Xa, a crucial step in blood clot formation, said Diener, co-chair of the study's adjudication committee.

"Apixaban was highly superior to aspirin. We had not anticipated that apixaban would show such a big difference compared with aspirin while showing no significant increase in major bleeds," he said. "Everyone had expected that a more powerful drug like apixaban would be associated with more severe bleeding complications compared to aspirin, but it wasn't."

The study's primary endpoint was the reduction of ischemic stroke (stroke caused by blockages in the brain's circulation), hemorrhagic stroke (stroke due to bleeding in the brain) and systemic embolism (blockages due to blood clots elsewhere in the body), he said. The primary safety endpoint was major bleeding incidents.

Up to 50 percent of all AF patients with moderate or high stroke risk are unsuitable for the most effective class of anti-clotting treatment known as vitamin K antagonists (VKA). That class includes the well-known drug warfarin.

All of the AVERROES patients were unsuitable for VKA therapy, which carries an increased risk of hemorrhage and requires frequent blood testing to monitor its effectiveness. For such patients the only alternate treatment is aspirin, which is just modestly effective, Diener said.

The patients in this study, all over age 50, were at moderate to high risk because they had at least one stroke risk factor in addition to AF, such as being age 75 or older, having high blood pressure, heart failure, diabetes or having a history of stroke or transient ischemic attack (a possible precursor of stroke), he explained.