Download Apixaban versus Warfarin in Patients with Atrial Fibrillation

Apixaban versus Warfarin in Patients
with Atrial Fibrillation
Christopher B. Granger, M.D., John H. Alexander, M.D., M.H.S., John J.V. McMurray, M.D., Renato D. Lopes,
M.D., Ph.D., Elaine M. Hylek, M.D., M.P.H., Michael Hanna, M.D., Hussein R. Al-Khalidi, Ph.D., Jack Ansell, M.D.,
Dan Atar, M.D., Alvaro Avezum, M.D., Ph.D., M. Cecilia Bahit, M.D., Rafael Diaz, M.D., J. Donald Easton, M.D.,
Justin A. Ezekowitz, M.B., B.Ch., Greg Flaker, M.D., David Garcia, M.D., Margarida Geraldes, Ph.D., Bernard J.
Gersh, M.D., Sergey Golitsyn, M.D., Ph.D., Shinya Goto, M.D., Antonio G. Hermosillo, M.D., Stefan H.
Hohnloser, M.D., John Horowitz, M.D., Puneet Mohan, M.D., Ph.D., Petr Jansky, M.D., Basil S. Lewis, M.D., Jose
Luis Lopez-Sendon, M.D., Prem Pais, M.D., Alexander Parkhomenko, M.D., Freek W.A. Verheugt, M.D., Ph.D.,
Jun Zhu, M.D., and Lars Wallentin, M.D., Ph.D., for the ARISTOTLE Committees and Investigators
N Engl J Med 2011;365(11):981-992.
R2 Min Hye Lee / Prof. Jin Bae Kim
Introduction
• Patients with atrial fibrillation : increased risk for stroke
• Wafarin and other vitamin K antagonists
 Highly effective treatments, reducing the risk of stroke by about two thirds
 Limitation : narrow therapeutic range, drug and food interactions, required
monitoring, risk of bleeding
• Apixaban
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Direct oral factor Xa inhibitor
Rapid absorption
12-hour half-life
25% renal excretion
• Apixaban for Reduction in Stroke and Other Thromboembolic
Events in Atrial Fibrillation(ARISTOTLE) trial
Methods
• Double-blind, double-dummy design
• Randomly assigned patients to treatment with apixaban or doseadjusted warfarin
• Compared apixaban (at a dose of 5 mg twice daily) with warfarin
(target INR, 2.0 to 3.0) in 18,201 patients with atrial fibrillation
and at least one additional risk factor for stroke
• The median duration of follow-up was 1.8 years
• The primary efficacy outcome : ischemic or hemorrhagic stroke or
systemic embolism
• The primary safety outcome : major bleeding
• The secondary safety outcome : composite of major bleeding and
clinically relevant non-major bleeding
Methods
• Atrial fibrillation or flutter at enrollment
• Two or more episodes of atrial fibrillation or flutter at least 2
weeks apart in the 12 months before enrollment
Inclusion criteria
Exclusion criteria
Age of at least 75 years
Atrial fibrillation due to a reversible cause
Previous stroke
Moderate or severe mitral stenosis
Transient ischemic attack
Conditions other than atrial fibrillation that
required anticoagulation (e.g., a prosthetic heart
valve)
Systemic embolism
Stroke within the previous 7 days
Symptomatic heart failure within the previous 3
months or left ventricular ejection fraction of no
more than 40%
Need for aspirin at a dose of >165 mg a day or
for both aspirin and clopidogrel
Diabetes mellitus
Severe renal insufficiency (serum creatinine level
of >2.5 mg per deciliter [221 μmol per liter]
Hypertension requiring pharmacologic treatment
Calculated creatinine clearance of <25 ml per
minute
Results
Results
Results
Results
Conclusion
• In patients with atrial fibrillation, apixaban was
superior to warfarin in preventing stroke or systemic
embolism, caused less bleeding, and resulted in lower
mortality