Edoxaban versus Warfarin in Patients with Atrial Fibrillation

被引：3786

作者：

Giugliano, Robert P. ^{[1
,2
]}

Ruff, Christian T. ^{[1
,2
]}

Braunwald, Eugene ^{[1
,2
]}

Murphy, Sabina A. ^{[1
,2
]}

Wiviott, Stephen D. ^{[1
,2
]}

Halperin, Jonathan L. ^{[3
]}

Waldo, Albert L. ^{[4
]}

Ezekowitz, Michael D. ^{[5
]}

Weitz, Jeffrey I. ^{[6
]}

Spinar, Jindrich ^{[7
]}

Ruzyllo, Witold ^{[8
]}

Ruda, Mikhail ^{[9
]}

Koretsune, Yukihiro ^{[10
]}

Betcher, Joshua ^{[11
]}

Shi, Minggao ^{[12
]}

Grip, Laura T. ^{[1
,2
]}

Patel, Shirali P. ^{[11
]}

Patel, Indravadan ^{[12
]}

Hanyok, James J. ^{[12
]}

Mercuri, Michele ^{[12
]}

Vogelmann, O. ^{[13
]}

Gonzalez, C. ^{[13
]}

Ahuad Guerrero, R. ^{[14
]}

Rodriguez, M. ^{[14
,62
,212
]}

Albisu, J. ^{[15
]}

Rosales, E. ^{[15
]}

Allall, O. ^{[16
]}

Reguero, M. ^{[16
]}

Alvarez, C. ^{[17
]}

Garcia, M. ^{[17
]}

Ameriso, S. ^{[18
]}

Ameriso, P. ^{[18
]}

Amuchastegui, M. ^{[19
]}

Caceres, M. ^{[19
]}

Beloscar, J. ^{[20
]}

Petrucci, J. ^{[20
]}

Berli, M. ^{[21
]}

Budassi, N. ^{[22
]}

Valle, M. ^{[22
]}

Bustamante Labarta, G. ^{[23
]}

Saravia, M. ^{[23
]}

Caccavo, A. ^{[24
]}

Fracaro, V. ^{[24
]}

Cartasegna, L. ^{[25
]}

Novas, V. ^{[25
]}

Caruso, O. ^{[26
]}

Saa Zarandon, R. ^{[26
]}

Colombo, H. ^{[27
]}

Morandini, M. ^{[27
]}

Cuello, J. ^{[28
]}

机构：

[1] Brigham & Womens Hosp, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Mt Sinai Med Ctr, New York, NY 10029 USA

[4] Univ Hosp Case Med Ctr, Cleveland, OH USA

[5] Thomas Jefferson Med Coll, Philadelphia, PA USA

[6] McMaster Univ, Hamilton, ON, Canada

[7] Univ Hosp, Brno, Czech Republic

[8] Inst Cardiol, Warsaw, Poland

[9] Cardiol Res Ctr, Moscow 121552, Russia

[10] Osaka Natl Hosp, Natl Hosp Org, Osaka, Japan

[11] Quintiles, Durham, NC USA

[12] Daiichi Sankyo Pharma Dev, Edison, NJ USA

[13] Hosp Alta Complejidad Presidente Juan Domingo Per, Formosa, For, Argentina

[14] Corporac Med Gral San Martin SA, San Martin, Bue, Argentina

[15] Inst Cardiovasc San Luis, San Luis, Sls, Argentina

[16] Hosp Cordoba, Cordoba, Crd, Argentina

[17] Hosp Italiano Reg Sur, Bahia Blanca, Bue, Argentina

[18] Inst Invest Neurol Raul Carrea FLENI, Buenos Aires, Bue, Argentina

[19] Hosp Privado Ctr Med Cordoba, Cordoba, Crd, Argentina

[20] Hosp Prov Centenario, Rosario, Sfe, Argentina

[21] Cedir, Santa Fe, Sfe, Argentina

[22] Hosp Interzonal Gen Agudos Dr Jose Penna, Bahia Blanca, Bue, Argentina

[23] Sanatorio Nuestra Senora Rosario, San Salvador De Jujuy, Juj, Argentina

[24] Clin Coronel Suarez, Coronel Suarez, Bue, Argentina

[25] Hosp Italiano La Plata, La Plata, Argentina

[26] Hosp Cent Mendoza, Mendoza, Men, Argentina

[27] Clin Colombo, Cordoba, Crd, Argentina

[28] Inst Invest Clin Bahia Blanca, Bahia Blanca, Bue, Argentina

[29] Hosp San Bernardo, Salta, Sal, Argentina

[30] Cedim Clin Privada, Ramos Mejia, Bue, Argentina

[31] Ctr Salud Norte, Munro, Bue, Argentina

[32] STAT Res, Ciudad Autonoma De Bs As, Cba, Argentina

[33] Ctr Privado Tomografia Computada Cordoba SA, Cordoba, Crd, Argentina

[34] Sanatorio Carmen, Salta, Argentina

[35] Hosp Espanol Mendoza, Godoy Cruz, Men, Argentina

[36] Cemic Saavedra, Ciudad Autonoma De Bs As, Cba, Argentina

[37] Hosp Aleman, Ciudad Autonoma De Bs As, Cba, Argentina

[38] Inst Invest Clin San Nicolas, San Nicolas, Bue, Argentina

[39] Clin Privada Prov SA, Merlo Buenos Aires, Bue, Argentina

[40] Unidad Cardiol Clin, Mar Del Plata, Bue, Argentina

[41] Hosp Espanol, Buenos Aires, Cba, Argentina

[42] Hosp Jose Maria Ramos Mejia, Buenos Aires, Bue, Argentina

[43] Ctr Invest Clin Litoral SRL, Santa Fe, Sfe, Argentina

[44] Clin Chutro SRL, Cordoba, Crd, Argentina

[45] Hosp Gen Agudos Donac Francisco Santojanni, Buenos Aires, Cba, Argentina

[46] Azira Clin Res, Pergamino, Bue, Argentina

[47] ALPI Inst Rehabil Marcelo Fitte, Caba, Bue, Argentina

[48] Serv Hosp San Justo SA, Buenos Aires, Bue, Argentina

[49] Inst Invest Clin Rosario, Rosario, Sfe, Argentina

[50] Sanatorio Julio Corzo, Rosario, Sjn, Argentina

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2013年 / 369卷 / 22期

关键词：

FACTOR XA INHIBITOR; ORAL ANTICOAGULANTS; STROKE; PHARMACOKINETICS; METAANALYSIS; GENERATION; PREVENTION; SAFETY;

D O I：

10.1056/NEJMoa1310907

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundEdoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. MethodsWe conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. ResultsThe annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). ConclusionsBoth once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)

引用

页码：2093 / 2104

页数：12

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