ARISTOTLE trial

ARISTOTLE study, 2011	TRC10339
[NCT00412984]	download pdf: apixaban \| antithrombotics for atrial fibrillation

Treatments

Studied treatment

apixaban 5mg twice daily

Control treatment

warfarin adjusted for an INR between 2 and 3

Treatments description

time within the therapeutic range (%)

mean 62% (median 66%)

Patients

subjects with atrial fibrillation and risk factors for stroke

Inclusion criteria

males and females >= 18 yrs with AF and one or more of the following risk factors for stroke: age �� 75, previous stroke TIA or Systemic Embolism Symptomatic congestive heart failure or left ventricular dysfunction with LVEF <=40% Diabetes mellitus or hypertension requiring pharmacological treatment

Baseline characteristics

age(mean)	70 yrs (median)
male(%)	65%
weight(mean)	82 kg (median)
systolic blood pressure(mean)	130 mmHg (median)
hypertension(%)	87.5%
diabete mellitus(%)	25%
prior TIA or stroke(%)	19.45%
left ventricular dysfunction(%)	35.5%
prior myocardial infarction(%)	14.2%
paroxysmal AF(%)	15.3%
subgroup test	a
CHADS2 Score (mean)	2.1
CHADS2 Score = 2 (%)	35.8%
CHADS2 Score = 3 (%)	30.2%

Method and design

Randomized effectives	9120 / 9081 (studied vs. control)
Design	Parallel groups
Blinding	double blind
Follow-up duration	1.8 yrs (median)
Number of centre	1034
Geographic area	39 countries
Hypothesis	Non inferiority
Primary endpoint	stroke or systemic embolism
Remarks

Remarks / Comments

Results

Endpoint Studied treat.
n/N Control treat.
n/N Graph RR [95% CI]

Coronary event

90 / 9088
102 / 9052
0,88 [0,66;1,17]

thrombo-embolic event (cerebral or systemic)

212 / 9120
265 / 9081
0,80 [0,67;0,95]

systemic thrombo-embolic complication

15 / 9120
17 / 9081
0,88 [0,44;1,76]

stroke (fatal and non fatal)

199 / 9120
250 / 9081
0,79 [0,66;0,95]

ischemic stroke

162 / 9120
175 / 9081
0,92 [0,75;1,14]

myocardial infarction (fatal and non fatal)

90 / 9120
102 / 9081
0,88 [0,66;1,16]

All cause death

603 / 9120
669 / 9081
0,90 [0,81;1,00]

Bleeding

2356 / 9120
3060 / 9081
0,77 [0,73;0,80]

Major bleeding

327 / 9120
462 / 9081
0,70 [0,61;0,81]

Haemmorhagic stroke

40 / 9120
78 / 9081
0,51 [0,35;0,75]

Gastrointestinal major bleeding

105 / 9120
119 / 9081
0,88 [0,68;1,14]

major or clinically relevant non-major bleeding

613 / 9120
877 / 9081
0,70 [0,63;0,77]

intracranial hemorrhage

52 / 9120
122 / 9081
0,42 [0,31;0,59] 0 2 1.0

Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
Relative risks
Endpoint	Studied treat.	Control treat.	Relative Risk	95% CI	Endpoint definition in the trial	Ref
Coronary event	90 / 9088 (1,0%)	102 / 9052 (1,1%)	0,88	[0,66;1,17]		16949
thrombo-embolic event (cerebral or systemic)	212 / 9120 (2,3%)	265 / 9081 (2,9%)	0,80	[0,67;0,95]	ITT population	14873
systemic thrombo-embolic complication	15 / 9120 (0,2%)	17 / 9081 (0,2%)	0,88	[0,44;1,76]		14873
stroke (fatal and non fatal)	199 / 9120 (2,2%)	250 / 9081 (2,8%)	0,79	[0,66;0,95]		14873
ischemic stroke	162 / 9120 (1,8%)	175 / 9081 (1,9%)	0,92	[0,75;1,14]	Ischemic or uncertain type of stroke	14873
myocardial infarction (fatal and non fatal)	90 / 9120 (1,0%)	102 / 9081 (1,1%)	0,88	[0,66;1,16]		14873
All cause death	603 / 9120 (6,6%)	669 / 9081 (7,4%)	0,90	[0,81;1,00]		14873
Bleeding	2356 / 9120 (25,8%)	3060 / 9081 (33,7%)	0,77	[0,73;0,80]		14873
Major bleeding	327 / 9120 (3,6%)	462 / 9081 (5,1%)	0,70	[0,61;0,81]	ISTH major bleeding	14873
Haemmorhagic stroke	40 / 9120 (0,4%)	78 / 9081 (0,9%)	0,51	[0,35;0,75]	Hemorrhagic stroke	14873
Gastrointestinal major bleeding	105 / 9120 (1,2%)	119 / 9081 (1,3%)	0,88	[0,68;1,14]		14873
major or clinically relevant non-major bleeding	613 / 9120 (6,7%)	877 / 9081 (9,7%)	0,70	[0,63;0,77]		14873
intracranial hemorrhage	52 / 9120 (0,6%)	122 / 9081 (1,3%)	0,42	[0,31;0,59]	ISTH major bleeding	14873
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 14873: Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz JApixaban versus Warfarin in Patients with Atrial Fibrillation.N Engl J Med 2011 Aug 27;: 16949: Mak KHCoronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials.BMJ Open 2012;2:

Endpoint	Events rate		Absolute risk reduction (ARR)
Absolute risk reduction (for a follow-up of 1.8 yrs (median))
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
Coronary event	9,90‰	1,13%	-0,14%
thrombo-embolic event (cerebral or systemic)	2,32%	2,92%	-0,59%
systemic thrombo-embolic complication	1,64‰	1,87‰	-0,02%
stroke (fatal and non fatal)	2,18%	2,75%	-0,57%
ischemic stroke	1,78%	1,93%	-0,15%
myocardial infarction (fatal and non fatal)	9,87‰	1,12%	-0,14%
All cause death	6,61%	7,37%	-0,76%
Bleeding	25,83%	33,70%	-7,86%
Major bleeding	3,59%	5,09%	-1,50%
Haemmorhagic stroke	4,39‰	8,59‰	-0,42%
Gastrointestinal major bleeding	1,15%	1,31%	-0,16%
major or clinically relevant non-major bleeding	6,72%	9,66%	-2,94%
intracranial hemorrhage	5,70‰	1,34%	-0,77%

Meta-analysis of all similar trials:

antithrombotics in atrial fibrillation for primary prevention of thromboembolic events

direct factor Xa inhibitors in atrial fibrillation for all type of patients

new oral anticoagulants in atrial fibrillation for all type of patients

Reference(s)

TrialResults-center ID	TRC10339
Trials register #	NCT00412984