Edoxaban versus warfarin in patients with atrial fibrillation

J 2013

Edoxaban versus warfarin in patients with atrial fibrillation

GIUGLIANO, Robert P.; Christian T. RUFF; Eugene BRAUNWALD; Sabina A. MURPHY; Stephen D. WIVIOTT et al.

Základní údaje

Originální název

Edoxaban versus warfarin in patients with atrial fibrillation

Autoři

Vydání

New England Journal of Medicine, Waltham, Massachusetts Medical Society, 2013, 0028-4793

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 54.420

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/13:00070758

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1056/NEJMoa1310907

UT WoS

000327467500007

Klíčová slova anglicky

Edoxaban; Warfarin; Atrial Fibrillation

Změněno: 13. 4. 2014 12:13, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

BACKGROUND: Edoxaban 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. METHODS: We 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. RESULTS: The 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). CONCLUSIONS: Both 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.)

Citovat

GIUGLIANO, Robert P.; Christian T. RUFF; Eugene BRAUNWALD; Sabina A. MURPHY; Stephen D. WIVIOTT; Jonathan L. HALPERIN; Albert L. WALDO; Michael D. EZEKOWITZ; Jeffrey I. WEITZ; Jindřich ŠPINAR; Witold RUZYLLO; Mikhail RUDA; Yukihiro KORETSUNE; Joshua BETCHER; Minggao SHI; Laura T. GRIP; Shirali P. PATEL; Indravadan PATEL; James J. HANYOK; Michele MERCURI a Elliot M. ANTMAN. Edoxaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine. Waltham: Massachusetts Medical Society, 2013, roč. 369, č. 22, s. 2093-2104. ISSN 0028-4793. Dostupné z: https://doi.org/10.1056/NEJMoa1310907.

@article{1138620,
   author = {Giugliano, Robert P. and Ruff, Christian T. and Braunwald, Eugene and Murphy, Sabina A. and Wiviott, Stephen D. and Halperin, Jonathan L. and Waldo, Albert L. and Ezekowitz, Michael D. and Weitz, Jeffrey I. and Špinar, Jindřich and Ruzyllo, Witold and Ruda, Mikhail and Koretsune, Yukihiro and Betcher, Joshua and Shi, Minggao and Grip, Laura T. and Patel, Shirali P. and Patel, Indravadan and Hanyok, James J. and Mercuri, Michele and Antman, Elliot M.},
   article_location = {Waltham},
   article_number = {22},
   doi = {https://doi.org/10.1056/NEJMoa1310907},
   keywords = {Edoxaban; Warfarin; Atrial Fibrillation},
   language = {eng},
   issn = {0028-4793},
   journal = {New England Journal of Medicine},
   title = {Edoxaban versus warfarin in patients with atrial fibrillation},
   volume = {369},
   year = {2013}
}

TY  - JOUR
ID  - 1138620
AU  - Giugliano, Robert P. - Ruff, Christian T. - Braunwald, Eugene - Murphy, Sabina A. - Wiviott, Stephen D. - Halperin, Jonathan L. - Waldo, Albert L. - Ezekowitz, Michael D. - Weitz, Jeffrey I. - Špinar, Jindřich - Ruzyllo, Witold - Ruda, Mikhail - Koretsune, Yukihiro - Betcher, Joshua - Shi, Minggao - Grip, Laura T. - Patel, Shirali P. - Patel, Indravadan - Hanyok, James J. - Mercuri, Michele - Antman, Elliot M.
PY  - 2013
TI  - Edoxaban versus warfarin in patients with atrial fibrillation
JF  - New England Journal of Medicine
VL  - 369
IS  - 22
SP  - 2093-2104
EP  - 2093-2104
PB  - Massachusetts Medical Society
SN  - 00284793
KW  - Edoxaban
KW  - Warfarin
KW  - Atrial Fibrillation
N2  - BACKGROUND: Edoxaban 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. METHODS: We 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. RESULTS: The 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). CONCLUSIONS: Both 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.)
ER  -

GIUGLIANO, Robert P.; Christian T. RUFF; Eugene BRAUNWALD; Sabina A. MURPHY; Stephen D. WIVIOTT; Jonathan L. HALPERIN; Albert L. WALDO; Michael D. EZEKOWITZ; Jeffrey I. WEITZ; Jindřich ŠPINAR; Witold RUZYLLO; Mikhail RUDA; Yukihiro KORETSUNE; Joshua BETCHER; Minggao SHI; Laura T. GRIP; Shirali P. PATEL; Indravadan PATEL; James J. HANYOK; Michele MERCURI a Elliot M. ANTMAN. Edoxaban versus warfarin in patients with atrial fibrillation. \textit{New England Journal of Medicine}. Waltham: Massachusetts Medical Society, 2013, roč.~369, č.~22, s.~2093-2104. ISSN~0028-4793. Dostupné z: https://doi.org/10.1056/NEJMoa1310907.

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