Final data show experimental agent better than aspirin at preventing stroke

Feb 10, 2011

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 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 , 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 (stroke caused by blockages in the brain's circulation), hemorrhagic stroke (stroke due to bleeding in the brain) and systemic embolism (blockages due to 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.

Patients were randomized to receive either apixaban at 5 milligrams (mg) twice a day (2.5 mg twice a day in selected patients) or between 81 mg and 324 mg of aspirin per day. The study's double-dummy design mandated that patients randomized to receive apixaban took an aspirin-placebo and those randomized to receive aspirin got an apixaban-placebo, he explained.

During an average of 1.1 years of follow up, the researchers found 51 strokes or systemic embolism events in the 2,808 patients taking apixaban compared to 113 strokes and systemic embolic events in the 2,791 patients taking aspirin. That represents an annual rate of 1.6 percent for apixaban vs. 3.6 percent for aspirin, meaning apixaban carries about half the relative risk of stroke or systemic embolism compared to aspirin. Although bleeding events were slightly higher with apixaban, the difference fell short of statistical significance.

The researchers will also report on a subgroup of patients with a history of stroke or transient ischemic attack (TIA), often a precursor to stroke.

"If validated by future studies I think this is the end of aspirin as a drug to prevent in patients with AF," he added.

Diener said the study's major limitation is the limited time period of observation, shortened further by the study's early conclusion. "AF patients need anticoagulation for the rest of their lives and we would have liked to see a much longer duration of the trial," he said.

"By evaluating the use of apixaban as a replacement for aspirin in AF patients who are unsuitable for VKA therapy, the AVERROES study is addressing an important unmet clinical need."

Explore further: Drug for rare blood disorder developed at Penn receives orphan drug status from EU

add to favorites email to friend print save as pdf

Related Stories

More advantages found for new drug: study

Feb 10, 2011

New findings from a McMaster University-led study of a drug recently identified to prevent stroke in patients with atrial fibrillation have been published in the high-impact New England Journal of Medicine (NEJM) today. ...

Success stops drug trial

Aug 31, 2010

The data monitoring committee of the AVERROES study, seeing overwhelming evidence of the success of apixaban in the prevention of stroke in patients with atrial fibrillation who are unsuitable for the conventional treatment ...

Blood-Thinning Drug Linked to Increased Bleeding in Brain

Sep 29, 2008

(PhysOrg.com) -- Patients who take the commonly used blood-thinning drug warfarin face larger amounts of bleeding in the brain and increased risk of mortality if they suffer a hemorrhagic stroke, new research from the University ...

Kidney disease increases the risk of stroke in patients

Mar 04, 2009

Chronic kidney disease increases the risk of stroke in patients with atrial fibrillation (AF), the most common type of heart arrhythmia, according to a new study by Kaiser Permanente researchers in the current online issue ...

Recommended for you

Expression of privilege in vaccine refusal

4 hours ago

Not all students returning to school this month will be up to date on their vaccinations. A new study conducted by Jennifer Reich, a researcher at the University of Colorado Denver, shows that the reasons why children may ...

Using computers to design drugs

Aug 22, 2014

Designing a new medicine is an expensive and time consuming business. Typically it takes around $2 billion and ten years for a new drug to move from its initial design in the lab, to the clinic. All the ...

Lilly psoriasis drug fares well in late-stage test

Aug 22, 2014

Drugmaker Eli Lilly and Co. said its potential psoriasis treatment fared better than both a fake drug and a competitor's product during late-stage testing on patients with the most common form of the skin disease.

User comments : 0