ACTIVE A trial

ACTIVE A study, 2009	TRC9345
[NCT00249873]	download pdf: aspirin + clopidogrel \| antithrombotics for atrial fibrillation

Treatments

Studied treatment	clopidogrel 75 mg daily + aspirin 75-100 mg daily
Control treatment	aspirin 75-100 mg daily alone

Patients

Patients with AF and at least one risk factor for stroke and who are not candidates for warfarin therapy

Inclusion criteria

at least one of the following risk factors: age >75 years, hypertension, prior stroke, prior transient ischemic attack, or prior systemic embolism, left ventricular ejection fraction <45%, peripheral vascular disease, or age 54-74 years and diabetes mellitus or coronary artery disease; patient not candidates for warfarin therapy; AF documented

Exclusion criteria

excessive risk of hemorrhage; prior intracerebral hemorrhage; peptic ulcer disease; requirement for oral vitamin K antagonist or clopidogrel therapy; significant thrombocytopenia; alcohol abuse

Baseline characteristics

age(mean)	71 y
male(%)	58%
prior stroke(%)	13%
prior myocardial infarction(%)	14%
paroxysmal AF(%)	36%
heart failure(%)	33%
subgroup test	b

Method and design

Randomized effectives	3772 / 3782 (studied vs. control)
Design	Parallel groups
Blinding	double blind
Follow-up duration	3.7 y
Primary endpoint	stroke, MI, systemic embolus, or vascular death

Results

Endpoints and data reported in the trial's publication(s)

Endpoint	Events (%)		Relative Risk	95% CI
Endpoint	Studied treat.	Control treat.	Relative Risk	95% CI
stroke, myocardial infarction, non�central nervous system systemic embolism, CV death	832 / 3772 (22,1%)	924 / 3782 (24,4%)	0,90	[0,83;0,98]
Any Stroke	296 / 3772 (7,8%)	408 / 3782 (10,8%)	0,73	[0,63;0,84]
Ischemic Stroke	235 / 3772 (6,2%)	343 / 3782 (9,1%)	0,69	[0,59;0,81]
Hemorrhagic Stroke	30 / 3772 (0,8%)	22 / 3782 (0,6%)	1,37	[0,79;2,37]
Stroke Of uncertain type	41 / 3772 (1,1%)	51 / 3782 (1,3%)	0,81	[0,54;1,21]
Fatal Stroke	70 / 3772 (1,9%)	93 / 3782 (2,5%)	0,75	[0,56;1,03]
Nondisabling Stroke	107 / 3772 (2,8%)	153 / 3782 (4,0%)	0,70	[0,55;0,89]
Disabling or fatal Stroke	198 / 3772 (5,2%)	267 / 3782 (7,1%)	0,74	[0,62;0,89]
Myocardial infarction	90 / 3772 (2,4%)	115 / 3782 (3,0%)	0,78	[0,60;1,03]
Non�central nervous system systemic embolism	54 / 3772 (1,4%)	56 / 3782 (1,5%)	0,97	[0,67;1,40]
Death from vascular causes	600 / 3772 (15,9%)	599 / 3782 (15,8%)	1,00	[0,91;1,11]
Death from any cause	825 / 3772 (21,9%)	841 / 3782 (22,2%)	0,98	[0,90;1,07]
Major bleeding	251 / 3772 (6,7%)	162 / 3782 (4,3%)	1,55	[1,28;1,88]
Severe major bleeding	190 / 3772 (5,0%)	122 / 3782 (3,2%)	1,56	[1,25;1,95]
Fatal major bleeding	42 / 3772 (1,1%)	27 / 3782 (0,7%)	1,56	[0,96;2,52]
Minor bleeding	408 / 3772 (10,8%)	175 / 3782 (4,6%)	2,34	[1,97;2,77]
Any bleeding	1014 / 3772 (26,9%)	651 / 3782 (17,2%)	1,56	[1,43;1,70]
Site of major bleeding* Gastrointestinal	132 / 3772 (3,5%)	68 / 3782 (1,8%)	1,95	[1,46;2,60]
Gastrointestinal, with transfusion	117 / 3772 (3,1%)	61 / 3782 (1,6%)	1,92	[1,42;2,61]
Intracranial bleeding	54 / 3772 (1,4%)	29 / 3782 (0,8%)	1,87	[1,19;2,93]
Extracranial bleeding	200 / 3772 (5,3%)	134 / 3782 (3,5%)	1,50	[1,21;1,85]

Endpoints used by the meta-analysis and data retained for this trial

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

thrombo-embolic event (cerebral or systemic)

832 / 3772
924 / 3782
0,90 [0,83;0,98]

stroke (fatal and non fatal)

296 / 3772
408 / 3782
0,73 [0,63;0,84]

ischemic stroke

235 / 3772
343 / 3782
0,69 [0,59;0,81]

myocardial infarction (fatal and non fatal)

90 / 3772
115 / 3782
0,78 [0,60;1,03]

All cause death

825 / 3772
841 / 3782
0,98 [0,90;1,07]

Bleeding

1014 / 3772
651 / 3782
1,56 [1,43;1,70]

Major bleeding

251 / 3772
162 / 3782
1,55 [1,28;1,88]

Minor bleeding

408 / 3772
175 / 3782
classic 2,34 [1,97;2,77]

Haemmorhagic stroke

30 / 3772
22 / 3782
classic 1,37 [0,79;2,37]

Fatal bleeding

42 / 3772
27 / 3782
classic 1,56 [0,96;2,52]

Cardiovascular death

600 / 3772
599 / 3782
1,00 [0,91;1,11]

Fatal stroke

70 / 3772
93 / 3782
0,75 [0,56;1,03]

TE event or ischemic stroke or systemic embolism

832 / 3772
924 / 3782
0,90 [0,83;0,98]

intracranial hemorrhage

54 / 3772
29 / 3782
classic 1,87 [1,19;2,93] 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
thrombo-embolic event (cerebral or systemic)	832 / 3772 (22,1%)	924 / 3782 (24,4%)	0,90	[0,83;0,98]	stroke, myocardial infarction, non�central nervous system systemic embolism, CV death
stroke (fatal and non fatal)	296 / 3772 (7,8%)	408 / 3782 (10,8%)	0,73	[0,63;0,84]	Any Stroke
ischemic stroke	235 / 3772 (6,2%)	343 / 3782 (9,1%)	0,69	[0,59;0,81]	Ischemic Stroke
myocardial infarction (fatal and non fatal)	90 / 3772 (2,4%)	115 / 3782 (3,0%)	0,78	[0,60;1,03]	Myocardial infarction
All cause death	825 / 3772 (21,9%)	841 / 3782 (22,2%)	0,98	[0,90;1,07]	Death from any cause
Bleeding	1014 / 3772 (26,9%)	651 / 3782 (17,2%)	1,56	[1,43;1,70]	Any bleeding
Major bleeding	251 / 3772 (6,7%)	162 / 3782 (4,3%)	1,55	[1,28;1,88]	Major bleeding
Minor bleeding	408 / 3772 (10,8%)	175 / 3782 (4,6%)	2,34	[1,97;2,77]	Minor bleeding
Haemmorhagic stroke	30 / 3772 (0,8%)	22 / 3782 (0,6%)	1,37	[0,79;2,37]	Hemorrhagic Stroke
Fatal bleeding	42 / 3772 (1,1%)	27 / 3782 (0,7%)	1,56	[0,96;2,52]	Fatal major bleeding
Cardiovascular death	600 / 3772 (15,9%)	599 / 3782 (15,8%)	1,00	[0,91;1,11]	Death from vascular causes
Fatal stroke	70 / 3772 (1,9%)	93 / 3782 (2,5%)	0,75	[0,56;1,03]	Fatal Stroke
TE event or ischemic stroke or systemic embolism	832 / 3772 (22,1%)	924 / 3782 (24,4%)	0,90	[0,83;0,98]	stroke, myocardial infarction, non�central nervous system systemic embolism, CV death
intracranial hemorrhage	54 / 3772 (1,4%)	29 / 3782 (0,8%)	1,87	[1,19;2,93]	Intracranial bleeding
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 0:

Endpoint	Events rate		Absolute risk reduction (ARR)
Absolute risk reduction (for a follow-up of 3.7 y)
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
thrombo-embolic event (cerebral or systemic)	22,06%	24,43%	-2,37%
stroke (fatal and non fatal)	7,85%	10,79%	-2,94%
ischemic stroke	6,23%	9,07%	-2,84%
myocardial infarction (fatal and non fatal)	2,39%	3,04%	-0,65%
All cause death	21,87%	22,24%	-0,37%
Bleeding	26,88%	17,21%	9,7%
Major bleeding	6,65%	4,28%	2,4%
Minor bleeding	10,82%	4,63%	6,2%
Haemmorhagic stroke	7,95‰	5,82‰	0,21%
Fatal bleeding	1,11%	7,14‰	0,40%
Cardiovascular death	15,91%	15,84%	0,07%
Fatal stroke	1,86%	2,46%	-0,60%
TE event or ischemic stroke or systemic embolism	22,06%	24,43%	-2,37%
intracranial hemorrhage	1,43%	7,67‰	0,66%

Meta-analysis of all similar trials:

antithrombotics in atrial fibrillation for primary prevention of thromboembolic events

Reference(s)

TrialResults-center ID	TRC9345
Trials register #	NCT00249873