Abstract
Background: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR). Methods and Results: The trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53-1.00) and 0.88 (95% CI, 0.57-1.35) (p.interaction. =0.078), for mortality were 0.91 (95% CI, 0.74-1.13) and 0.91 (95% CI, 0.71-1.16) (p. interaction. =0.34), and for (Pinteraction=0.0778),For mortality were 0.91 (95% CI,0.74-1.13) and 0.91 (95%CI,0.71-1.16) (P interaction=0.34),and for major bleeding were 0.50 (95% CI, 0.36-0.70) and 0.75 (95% CI, 0.58-0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR. Conclusions: The benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers' and patients' predicted quality of international normalized ratio control.
| Original language | English |
|---|---|
| Pages (from-to) | 2166-2176 |
| Number of pages | 11 |
| Journal | Circulation |
| Volume | 127 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - Jun 4 2013 |
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Keywords
- Anticoagulation
- Apixaban
- Atrial Fibrillation
- Bleeding
- Stroke
- Warfarin
ASJC Scopus subject areas
- Physiology (medical)
- Cardiology and Cardiovascular Medicine
Cite this
Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for Stroke prevention in atrial fibrillation. / Wallentin, Lars; Lopes, Renato D.; Hanna, Michael; Thomas, Laine; Hellkamp, Anne; Nepal, Sunil; Hylek, Elaine M.; Al-Khatib, Sana M.; Alexander, John H.; Alings, Marco; Amerena, John; Ansell, Jack; Aylward, Philip; Bartunek, Jozef; Commerford, Patrick; De Caterina, Raffaele; Erol, Cetin; Harjola, Veli Pekka; Held, Claes; Horowitz, John D.; Huber, Kurt; Husted, Steen; Keltai, M.; Lanas, Fernando; Lisheng, Liu; McMurray, John J V; Oh, Byung Hee; Rosenqvist, Mårten; Ruzyllo, Witold; Steg, Philippe Gabriel; Vinereanu, Dragos; Xavier, Denis; Granger, Christopher B.
In: Circulation, Vol. 127, No. 22, 04.06.2013, p. 2166-2176.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for Stroke prevention in atrial fibrillation
AU - Wallentin, Lars
AU - Lopes, Renato D.
AU - Hanna, Michael
AU - Thomas, Laine
AU - Hellkamp, Anne
AU - Nepal, Sunil
AU - Hylek, Elaine M.
AU - Al-Khatib, Sana M.
AU - Alexander, John H.
AU - Alings, Marco
AU - Amerena, John
AU - Ansell, Jack
AU - Aylward, Philip
AU - Bartunek, Jozef
AU - Commerford, Patrick
AU - De Caterina, Raffaele
AU - Erol, Cetin
AU - Harjola, Veli Pekka
AU - Held, Claes
AU - Horowitz, John D.
AU - Huber, Kurt
AU - Husted, Steen
AU - Keltai, M.
AU - Lanas, Fernando
AU - Lisheng, Liu
AU - McMurray, John J V
AU - Oh, Byung Hee
AU - Rosenqvist, Mårten
AU - Ruzyllo, Witold
AU - Steg, Philippe Gabriel
AU - Vinereanu, Dragos
AU - Xavier, Denis
AU - Granger, Christopher B.
PY - 2013/6/4
Y1 - 2013/6/4
N2 - Background: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR). Methods and Results: The trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53-1.00) and 0.88 (95% CI, 0.57-1.35) (p.interaction. =0.078), for mortality were 0.91 (95% CI, 0.74-1.13) and 0.91 (95% CI, 0.71-1.16) (p. interaction. =0.34), and for (Pinteraction=0.0778),For mortality were 0.91 (95% CI,0.74-1.13) and 0.91 (95%CI,0.71-1.16) (P interaction=0.34),and for major bleeding were 0.50 (95% CI, 0.36-0.70) and 0.75 (95% CI, 0.58-0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR. Conclusions: The benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers' and patients' predicted quality of international normalized ratio control.
AB - Background: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR). Methods and Results: The trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53-1.00) and 0.88 (95% CI, 0.57-1.35) (p.interaction. =0.078), for mortality were 0.91 (95% CI, 0.74-1.13) and 0.91 (95% CI, 0.71-1.16) (p. interaction. =0.34), and for (Pinteraction=0.0778),For mortality were 0.91 (95% CI,0.74-1.13) and 0.91 (95%CI,0.71-1.16) (P interaction=0.34),and for major bleeding were 0.50 (95% CI, 0.36-0.70) and 0.75 (95% CI, 0.58-0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR. Conclusions: The benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers' and patients' predicted quality of international normalized ratio control.
KW - Anticoagulation
KW - Apixaban
KW - Atrial Fibrillation
KW - Bleeding
KW - Stroke
KW - Warfarin
UR - http://www.scopus.com/inward/record.url?scp=84878535107&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878535107&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.112.142158
DO - 10.1161/CIRCULATIONAHA.112.142158
M3 - Article
C2 - 23640971
AN - SCOPUS:84878535107
VL - 127
SP - 2166
EP - 2176
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 22
ER -