ARISTOTLE

(Apixaban for the Prevention of Stroke in

Subjects With Atrial Fibrillation)

ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation)

• An active-controlled, randomized, double-blind trial to compare the safety and

efficacy of apixaban and warfarin in preventing stroke and systemic embolism

in subjects with AF and risk factors for stroke

• Population and treatment:

18 201 AF patients randomized to apixaban (5 mg orally twice daily) or

warfarin (target INR of 2.0 to 3.0)

• Subanalysis:

ARISTOTLE subcohort separated by LV function and symptom status: 2736

patients with LV systolic dysfunction, having an LVEF <40% with or without

clinical heart failure; 3207 patients with HF-PEF (ie, >40%); and 8728 with

neither symptoms nor LV systolic dysfunction, with LVEF >40%

JJV McMurray (University of Glasgow, Scotland) European Society of Cardiology Heart Failure Congress 2012

AF=atrial fibrillation; LV=left ventricular; HF=heart failure; LVEF=left ventricular ejection fraction;

HF-PEF=heart failure with preserved ejection fraction

ARISTOTLE: Results (efficacy)

End point Apixaban

(%/year)

Warfarin

(%/year)

p for

interaction

Stroke or systemic embolism* 0.213

LV systolic dysfunction 0.99 1.80

HF-PEF 1.51 1.54

No LV systolic dysfunction of HF 1.16 1.58

All 1.27 1.60

*Primary end point

• Stroke or systemic embolism* risk

similarly low among the three

patient categories and overall

significantly reduced for apixaban

vs warfarin

Outcomes in patients with AF by LV

systolic function and HF status

Outcomes in patients with AF by LV

systolic function and HF status

ARISTOTLE: Results (safety)

End point Apixaban

(%/year)

Warfarin

(%/year)

p for

interaction

SSE/death 0.632

LV systolic dysfunction 7.76 8.37

HF-PEF 5.07 5.57

No LV systolic dysfunction of HF 3.14 3.79

All 4.49 5.04

SSE/major bleeding/death 0.589

LV systolic dysfunction 10.11 10.81

HF-PEF 6.71 7.76

No LV systolic dysfunction or HF 4.78 5.76

All 6.13 7.20

*Primary end point

HF-PEF=heart failure with preserved ejection fraction

• Event rates increased when SSE

was combined with the competing

risk of all-cause mortality;

apixaban maintained its

significant advantage over

warfarin

• Event rates increased more, and

apixaban superiority persisted,

with the addition of major

bleeding to the end point

ARISTOTLE: Commentary*

*All comments from ARISTOTLE "heart-failure substudy" sees apixaban stroke protection regardless

of HF, LV function (http://www.theheart.org/article/1404439.do)

"[AF patients with HF, LV systolic dysfunction, or both] had worse outcomes than

patients with atrial fibrillation and neither heart failure nor systolic dysfunction,

although this was primarily driven by mortality and not by thromboembolic risk,

which was actually quite low in all groups."

- Dr John JV McMurray

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