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

Bristol-Myers Squibb Company and Pfizer Inc. 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 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 (pAbout ELIQUIS ELIQUIS is the approved trade name for apixaban in Europe and the proposed trade name in the U.S. ELIQUIS is not approved for the prevention of stroke or systemic embolism in patients with atrial fibrillation in any country. Bristol-Myers Squibb and Pfizer recently announced the first regulatory approval for ELIQUIS in the 27 countries of the European Union (EU) for the prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery. ELIQUIS is being investigated within the EXPANSE Clinical Trials Program, which is projected to include nearly 60,000 patients worldwide across multiple indications and patient populations and includes a total of nine completed or ongoing, randomized, double-blind Phase 3 trials, including ARISTOTLE. The ELIQUIS atrial fibrillation clinical trial program, which includes ARISTOTLE and AVERROES, was designed to comprehensively evaluate ELIQUIS in approximately 24,000 patients with atrial fibrillation, including patients who are expected or demonstrated to be unsuitable for vitamin K antagonist (VKA) therapy. In addition to stroke prevention in patients with atrial fibrillation and the prevention of VTE in patients who have undergone total hip or total knee replacement surgery, ELIQUIS is being investigated in Phase 3 trials for the treatment of VTE and the prevention of VTE in hospitalized acutely ill medical patients. About the Bristol-Myers Squibb/Pfizer Collaboration In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize ELIQUIS, an investigational oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb's long-standing strengths in cardiovascular drug development and commercialization with Pfizer’s global scale and expertise in this field.