TY - JOUR
T1 - Apixaban versus warfarin in patients with atrial fibrillation
AU - Granger, Christopher B
AU - Alexander, John H
AU - McMurray, John J V
AU - Lopes, Renato D
AU - Hylek, Elaine M
AU - Hanna, Michael
AU - Al-Khalidi, Hussein R
AU - Ansell, Jack
AU - Atar, Dan
AU - Avezum, Alvaro
AU - Bahit, M Cecilia
AU - Diaz, Rafael
AU - Easton, J Donald
AU - Ezekowitz, Justin A
AU - Flaker, Greg
AU - Garcia, David
AU - Geraldes, Margarida
AU - Gersh, Bernard J
AU - Golitsyn, Sergey
AU - Goto, Shinya
AU - Hermosillo, Antonio G
AU - Hohnloser, Stefan H
AU - Horowitz, John
AU - Mohan, Puneet
AU - Jansky, Petr
AU - Lewis, Basil S
AU - Lopez-Sendon, Jose Luis
AU - Pais, Prem
AU - Parkhomenko, Alexander
AU - Verheugt, Freek W A
AU - Zhu, Jun
AU - Wallentin, Lars
AU - ARISTOTLE Committees and Investigators
PY - 2011/9/15
Y1 - 2011/9/15
N2 - BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42).CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).
AB - BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42).CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).
KW - Aged
KW - Anticoagulants
KW - Atrial Fibrillation
KW - Double-Blind Method
KW - Factor Xa Inhibitors
KW - Female
KW - Follow-Up Studies
KW - Hemorrhage
KW - Humans
KW - International Normalized Ratio
KW - Kaplan-Meier Estimate
KW - Male
KW - Middle Aged
KW - Pyrazoles
KW - Pyridones
KW - Stroke
KW - Thromboembolism
KW - Treatment Outcome
KW - Warfarin
U2 - 10.1056/NEJMoa1107039
DO - 10.1056/NEJMoa1107039
M3 - Article
C2 - 21870978
SN - 0028-4793
VL - 365
SP - 981
EP - 992
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 11
ER -