Apixaban versus Warfarin in Patients with Atrial Fibrillation

被引：6769

作者：

Granger, Christopher B. ^{[1
]}

Alexander, John H. ^{[1
]}

McMurray, John J. V. ^{[2
]}

Lopes, Renato D. ^{[1
]}

Hylek, Elaine M. ^{[3
]}

Hanna, Michael ^{[4
]}

Al-Khalidi, Hussein R. ^{[1
]}

Ansell, Jack ^{[5
]}

Atar, Dan ^{[6
]}

Avezum, Alvaro ^{[7
]}

Cecilia Bahit, M. ^{[8
]}

Diaz, Rafael ^{[8
]}

Easton, J. Donald ^{[9
]}

Ezekowitz, Justin A. ^{[10
]}

Flaker, Greg ^{[11
]}

Garcia, David ^{[12
]}

Geraldes, Margarida ^{[4
]}

Gersh, Bernard J. ^{[13
]}

Golitsyn, Sergey ^{[14
]}

Goto, Shinya ^{[15
]}

Hermosillo, Antonio G. ^{[16
]}

Hohnloser, Stefan H. ^{[17
]}

Horowitz, John ^{[18
]}

Mohan, Puneet ^{[4
]}

Jansky, Petr ^{[19
]}

Lewis, Basil S. ^{[20
]}

Luis Lopez-Sendon, Jose ^{[21
]}

Pais, Prem ^{[22
]}

Parkhomenko, Alexander ^{[23
]}

Verheugt, Freek W. A. ^{[24
]}

Zhu, Jun ^{[25
]}

Wallentin, Lars ^{[26
]}

机构：

[1] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA

[2] Univ Glasgow, Glasgow, Lanark, Scotland

[3] Boston Univ, Med Ctr, Boston, MA USA

[4] Bristol Myers Squibb Co, Princeton, NJ USA

[5] Lenox Hill Hosp, New York, NY 10021 USA

[6] Oslo Univ Hosp, Oslo, Norway

[7] Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil

[8] ECLA Estudios Cardiol Latinoamer, Rosario, Santa Fe, Argentina

[9] Univ Calif San Francisco, San Francisco, CA 94143 USA

[10] Univ Alberta, Edmonton, AB, Canada

[11] Univ Missouri Hlth Care, Columbia, MO USA

[12] Univ New Mexico, Albuquerque, NM 87131 USA

[13] Mayo Clin, Rochester, MN USA

[14] Russian Cardiol Res Ctr, Moscow, Russia

[15] Tokai Univ, Sch Med, Kanagawa 2591100, Japan

[16] Inst Nacl Cardiol, Tlalpan Cp, Mexico

[17] Goethe Univ Frankfurt, Frankfurt, Germany

[18] Univ Adelaide, Adelaide, SA, Australia

[19] Motol Univ Hosp, Prague, Czech Republic

[20] Lady Davis Carmel Med Ctr, Haifa, Israel

[21] Hosp Univ La Paz, Madrid, Spain

[22] St Johns Med Coll, Bangalore, Karnataka, India

[23] Inst Cardiol, Kiev, Ukraine

[24] Onze Lieve Vrouw Hosp, Amsterdam, Netherlands

[25] Fuwai Hosp, Beijing, Peoples R China

[26] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2011年 / 365卷 / 11期

关键词：

THERAPY; ANTICOAGULATION; DABIGATRAN; EVENTS; STROKE; TRIAL; RISK;

D O I：

10.1056/NEJMoa1107039

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.govnumber, NCT00412984.)

引用

页码：981 / 992

页数：12

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