ACTIVE W trial

ACTIVE W study, 2006	TRC4721
[NCT00243178]	download pdf: aspirin + clopidogrel \| antithrombotics for atrial fibrillation

Treatments

Studied treatment	clopidogrel (75 mg per day) plus aspirin (75–100 mg per day)
Control treatment	oral anticoagulation therapy (target international normalised ratio of 2·0–3·0)

Patients

Patients with atrial fibrillation plus one or more risk factor for stroke

Inclusion criteria

electrocardiographicevidence of atrial fibrillation and at least one of the following: age 75 years or older; on treatment for systemic hypertension; previous stroke, transient ischaemic attack, or non-CNS systemic embolus; left ventricular dysfunction with left ventricular ejection fraction less than 45%; peripheral arterial disease; if patients were aged 55–74 years and did not have one of the other inclusion criteria they were required to have either diabetes mellitus requiring drug therapy or previous coronary artery disease

Exclusion criteria

contraindication for clopidogrel or for oral anticoagulant (such as prosthetic mechanical heart valve); documented peptic ulcer disease within the previous 6 months; previous intracerebral haemorrhage; signifi cant thrombocytopenia (platelet count

Baseline characteristics

subgroup test

Method and design

Randomized effectives	3335 / 3371 (studied vs. control)
Design	Parallel groups
Blinding	open
Follow-up duration	1.28 y (median)
Premature discontinuation	Premature discontinuation for safety reason
Lost to follow-up	22 (0.33%)
Hypothesis	Superiority
Primary endpoint	stroke, non-CNS systemic embolus
Withdrawals (T1/T0)	413 (12.38%) / 224 (6.64%)

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
Composite of stroke, non CNS embolus, myocardial infarction, vascular death	234 / 3335 (7,0%)	165 / 3371 (4,9%)	1,43	[1,18;1,74]
Non-CNS embolus	18 / 3335 (0,5%)	4 / 3371 (0,1%)	4,55	[1,54;13,43]
Myocardial infarction	36 / 3335 (1,1%)	23 / 3371 (0,7%)	1,58	[0,94;2,66]
Stroke	100 / 3335 (3,0%)	59 / 3371 (1,8%)	1,71	[1,25;2,36]
Ischaemic Stroke	90 / 3335 (2,7%)	42 / 3371 (1,2%)	2,17	[1,51;3,11]
Haemorrhagic Stroke	5 / 3335 (0,1%)	15 / 3371 (0,4%)	0,34	[0,12;0,93]
Non-disabling Stroke	42 / 3335 (1,3%)	17 / 3371 (0,5%)	2,50	[1,42;4,38]
Disabling Stroke	58 / 3335 (1,7%)	40 / 3371 (1,2%)	1,47	[0,98;2,19]
Fatal Stroke	14 / 3335 (0,4%)	15 / 3371 (0,4%)	0,94	[0,46;1,95]
Total mortality	159 / 3335 (4,8%)	158 / 3371 (4,7%)	1,02	[0,82;1,26]
Vascular death	120 / 3335 (3,6%)	106 / 3371 (3,1%)	1,14	[0,89;1,48]
Non-vascular death	39 / 3335 (1,2%)	52 / 3371 (1,5%)	0,76	[0,50;1,15]
Major Haemorrhage(includes severe and fatal)	101 / 3335 (3,0%)	93 / 3371 (2,8%)	1,10	[0,83;1,45]
Severe Haemorrhage	71 / 3335 (2,1%)	66 / 3371 (2,0%)	1,09	[0,78;1,52]
Fatal Haemorrhage	7 / 3335 (0,2%)	11 / 3371 (0,3%)	0,64	[0,25;1,66]
Minor Haemorrhage	568 / 3335 (17,0%)	481 / 3371 (14,3%)	1,19	[1,07;1,33]
Total Haemorrhage	644 / 3335 (19,3%)	555 / 3371 (16,5%)	1,17	[1,06;1,30]
Net benefit Primary outcome and major bleed	316 / 3335 (9,5%)	229 / 3371 (6,8%)	1,39	[1,18;1,64]
Net benefit Primary outcome, major bleed, and death	348 / 3335 (10,4%)	271 / 3371 (8,0%)	1,30	[1,12;1,51]

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)

234 / 3335
165 / 3371
1,43 [1,18;1,74]

stroke (fatal and non fatal)

100 / 3335
59 / 3371
classic 1,71 [1,25;2,36]

ischemic stroke

90 / 3335
42 / 3371
classic 2,17 [1,51;3,11]

All cause death

159 / 3335
158 / 3371
1,02 [0,82;1,26]

Bleeding

644 / 3335
555 / 3371
1,17 [1,06;1,30]

Major bleeding

101 / 3335
93 / 3371
1,10 [0,83;1,45]

Minor bleeding

568 / 3335
481 / 3371
1,19 [1,07;1,33]

Haemmorhagic stroke

5 / 3335
15 / 3371
0,34 [0,12;0,93]

Fatal bleeding

7 / 3335
11 / 3371
0,64 [0,25;1,66]

Cardiovascular death

120 / 3335
106 / 3371
1,14 [0,89;1,48]

Fatal stroke

14 / 3335
15 / 3371
0,94 [0,46;1,95] 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)	234 / 3335 (7,0%)	165 / 3371 (4,9%)	1,43	[1,18;1,74]	Composite of stroke, non CNS embolus, myocardial infarction, vascular death
stroke (fatal and non fatal)	100 / 3335 (3,0%)	59 / 3371 (1,8%)	1,71	[1,25;2,36]	Stroke
ischemic stroke	90 / 3335 (2,7%)	42 / 3371 (1,2%)	2,17	[1,51;3,11]	Ischaemic Stroke
All cause death	159 / 3335 (4,8%)	158 / 3371 (4,7%)	1,02	[0,82;1,26]	Total mortality
Bleeding	644 / 3335 (19,3%)	555 / 3371 (16,5%)	1,17	[1,06;1,30]	Total Haemorrhage
Major bleeding	101 / 3335 (3,0%)	93 / 3371 (2,8%)	1,10	[0,83;1,45]	Major Haemorrhage(includes severe and fatal)
Minor bleeding	568 / 3335 (17,0%)	481 / 3371 (14,3%)	1,19	[1,07;1,33]	Minor Haemorrhage
Haemmorhagic stroke	5 / 3335 (0,1%)	15 / 3371 (0,4%)	0,34	[0,12;0,93]	Haemorrhagic Stroke
Fatal bleeding	7 / 3335 (0,2%)	11 / 3371 (0,3%)	0,64	[0,25;1,66]	Fatal Haemorrhage
Cardiovascular death	120 / 3335 (3,6%)	106 / 3371 (3,1%)	1,14	[0,89;1,48]	Vascular death
Fatal stroke	14 / 3335 (0,4%)	15 / 3371 (0,4%)	0,94	[0,46;1,95]	Fatal Stroke
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 1.28 y (median))
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
thrombo-embolic event (cerebral or systemic)	7,02%	4,89%	2,1%
stroke (fatal and non fatal)	3,00%	1,75%	1,2%
ischemic stroke	2,70%	1,25%	1,5%
All cause death	4,77%	4,69%	0,08%
Bleeding	19,31%	16,46%	2,8%
Major bleeding	3,03%	2,76%	0,27%
Minor bleeding	17,03%	14,27%	2,8%
Haemmorhagic stroke	1,50‰	4,45‰	-0,30%
Fatal bleeding	2,10‰	3,26‰	-0,12%
Cardiovascular death	3,60%	3,14%	0,45%
Fatal stroke	4,20‰	4,45‰	-0,03%

Meta-analysis of all similar trials:

antithrombotics in atrial fibrillation for primary prevention of thromboembolic events

Reference(s)

TrialResults-center ID	TRC4721
Trials register #	NCT00243178