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ELIQUIS? (apixaban) was Superior to Warfarin for the Reduction of Stroke or Systemic Embolism with Significantly Less Major Bleeding in Patients with Atrial Fibrillation in Phase 3 ARISTOTLE Trial

Sunday, August 28, 2011 2:01 AM

ARISTOTLE Demonstrated that ELIQUIS is the First Oral Anticoagulant to Significantly Reduce All-Cause Death ELIQUIS, Compared to Standard of Care Warfarin, Significantly Reduced:

Bristol-Myers Squibb Company (NYSE:BMY) and Pfizer Inc. (NYSE:PFE) today announced the main results of the Phase 3 clinical trial ARISTOTLE, which evaluated ELIQUIS® (apixaban) compared to warfarin for the prevention of stroke or systemic embolism in 18,201 patients with atrial fibrillation and at least one risk factor for stroke. In the ARISTOTLE trial, ELIQUIS as compared with warfarin significantly reduced the risk of stroke or systemic embolism by 21 percent, major bleeding by 31 percent, and mortality by 11 percent. Results were presented today during the Hot Line session at the European Society of Cardiology Congress in Paris, France, and published in The New England Journal of Medicine.

Conducted in 1,034 centers in 39 countries, the study was coordinated by the Duke Clinical Research Institute, Durham, N.C., and Uppsala Clinical Research Institute, Uppsala, Sweden.

"The risk for stroke in patients with atrial fibrillation is a major public health concern in an aging population," said Dr. Christopher B. Granger, professor of medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, N.C., and lead investigator of the study. "We are therefore encouraged by the outcome of the ARISTOTLE trial, which showed that apixaban, as compared with warfarin, significantly reduced the risk of stroke or systemic embolism, major bleeding, and mortality."

ELIQUIS, a new oral direct Factor Xa inhibitor, is part of a class of agents being studied for their potential to prevent and treat blood clots.

Atrial fibrillation is the most common sustained cardiac arrhythmia, or irregular heart beat. It is estimated that more than 5 million Americans and 6 million individuals in the European Union have atrial fibrillation. The lifetime risk of atrial fibrillation is estimated to be approximately one in four for individuals 40 years of age or older. The most serious medical issue for individuals with atrial fibrillation is the increased risk of stroke, which is five times higher in people with atrial fibrillation than those without atrial fibrillation. In fact, 15 percent of all strokes are attributable to atrial fibrillation in the U.S. Additionally, strokes due to atrial fibrillation are more burdensome than strokes not due to atrial fibrillation. Atrial fibrillation-related strokes are more severe than other strokes with an associated 30-day mortality of 24 percent and a 50 percent likelihood of death within one year.

About ARISTOTLE

ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), a randomized, double-blind, multicenter, head-to-head trial, included 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The mean CHADS2 risk score for the study population was 2.1. Patients were randomized to receive either apixaban (n=9,120) 5 mg twice daily (2.5 mg twice daily in selected patients) or warfarin (n=9,081) dosed to achieve a target INR (International Normalized Ratio) of 2.0-3.0.

The key study outcomes were prespecified in a hierarchical manner that sequentially tested apixaban versus warfarin for noninferiority on the composite endpoint of stroke or systemic embolism; superiority on the composite endpoint of stroke or systemic embolism; superiority on major bleeding; and superiority on all-cause death. The efficacy analyses included all randomized patients ("intention to treat"); bleeding analyses were "on treatment" and included all randomized patients who received at least one dose of study drug. ELIQUIS demonstrated non-inferiority (p<0.001) for the primary efficacy outcome, composite of stroke or systemic embolism, compared with warfarin. The relative risk reduction was 21 percent with annual event rates of 1.27 percent for ELIQUIS and 1.60 percent for warfarin in an intention to treat analysis.


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