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