AFASAK II (warfarin low dose vs warfarin standard dose) Trial

AFASAK II (warfarin low dose vs warfarin standard dose) study, 1998	TRC2619
	download pdf: warfarin low dose \| antithrombotics for atrial fibrillation

Treatments

Studied treatment	warfarin fixed low dose (1.25 mg/d)
Control treatment	warfarin standard dose(target INR 2-3)
Concomittant treatment	Patients are informed not to take aspirin or NSAI drugs during the study period. If NSAI drugs are temporarily needed,the study treatment is interrupted for safety reasons.
Remarks	The trial includes 4 arms:fixed low dose warfarin (1.25mg/d),fixed low dose warfarin (1.25mg/d)+ aspirin 300mg,aspirin 300 mg and conventional warfarin therapy(target INR 2-3). The protocol allows 4 weeks per year without study treatment.

Patients

chronic non valvular atrial fibrillation

Inclusion criteria

age>18;non valvuar atrial fibrillation documented on ECG twice,with an interval of at least one month.

Exclusion criteria

Patient under 60 with lone atrial fibrillation;thrombo-embolic event within the last 6 months;systolic blood pressure over 180mmHg or diastolic blood pressure over 100 mmHg;mitral stenosis;contraindication for warfarin or aspirin therapy;warfarin therapy based on other medical conditions,medical conditions requiring permanent nonsteroidal antiinflammatory drug therapy;noncompliance(alcoholism,psychiatric disease,dementia and foreign language);pregnancy and breast feeding.

Baseline characteristics

age(mean)	73.7
male(%)	51
systolic blood pressure(mean)	148.45
diastolic blood pressure(mean)	86.85
hypertension(%)	44
diabete mellitus(%)	14
prior TIA(%)	2
prior stroke(%)	4.5
left atrial dimension(mean in mm)	25.65
heart failure(%)	69.5
current smoker(%)	30
subgroup test	a

Method and design

Randomized effectives	167 / 170 (studied vs. control)
Design	Parallel groups
Blinding	Open
Follow-up duration	3.5 years
Premature discontinuation	Premature discontinuation for futility
Lost to follow-up	no lost to follow up
Number of centre	1
Geographic area	Denmark
Hypothesis	superiority
Primary endpoint	all stroke or systemic thromboembolic event
Remarks	Mean follow-up duration was not reported. The discontinuation of study treatment was reported globally(25.1% for reasons other than primary or secondary adverse events).Though the primary analysis of the study was made according to an "on treatment" approach ,an "intention to treat" analysis was performed for thrombo-embolic events to allow comparison with other studies.
Withdrawals (T1/T0)	nr / nr

Results

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

thrombo-embolic event (cerebral or systemic)

6 / 167
4 / 170
classic 1,53 [0,44;5,31]

systemic thrombo-embolic complication

1 / 167
2 / 170
classic 0,51 [0,05;5,56]

stroke (fatal and non fatal)

13 / 167
10 / 170
classic 1,32 [0,60;2,93]

ischemic stroke

6 / 167
4 / 170
classic 1,53 [0,44;5,31]

myocardial infarction (fatal and non fatal)

6 / 167
4 / 170
classic 1,53 [0,44;5,31]

All cause death

6 / 167
17 / 170
0,36 [0,15;0,89]

Major bleeding

3 / 167
4 / 170
classic 0,76 [0,17;3,36]

Minor bleeding

21 / 167
42 / 170
0,51 [0,32;0,82]

Haemmorhagic stroke

0 / 167
1 / 170
classic 0,20 [0,00;14,84]

Cardiovascular death

3 / 167
5 / 170
classic 0,61 [0,15;2,52]

Fatal stroke

2 / 167
0 / 170
classic 9,16 [0,15;567,68]

TE event or ischemic stroke or systemic embolism

6 / 167
4 / 170
classic 1,53 [0,44;5,31]

intracranial hemorrhage

1 / 167
2 / 170
classic 0,51 [0,05;5,56]

Adverse events

0 / 167
0 / 170
classic 1,02 [0,00;259,15] 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)	6 / 167 (3,6%)	4 / 170 (2,4%)	1,53	[0,44;5,31]
systemic thrombo-embolic complication	1 / 167 (0,6%)	2 / 170 (1,2%)	0,51	[0,05;5,56]	systemic thromboembolic events in extremities,kidneys,mesenteric arteries,lungs,spleen,retina or grafts;verified using angiography,surgery,scintigraphy or autopsy
stroke (fatal and non fatal)	13 / 167 (7,8%)	10 / 170 (5,9%)	1,32	[0,60;2,93]	acute onset of a focal neurogical deficit of presumed vascular genesis lasting for 24 hours or more
ischemic stroke	6 / 167 (3,6%)	4 / 170 (2,4%)	1,53	[0,44;5,31]
myocardial infarction (fatal and non fatal)	6 / 167 (3,6%)	4 / 170 (2,4%)	1,53	[0,44;5,31]	2 of the following criteria:history of typical chest pain,serial creatine kinase-MB changes typical of acute myocardial infarction, or ECG changes typical of acute myocardial infarction
All cause death	6 / 167 (3,6%)	17 / 170 (10,0%)	0,36	[0,15;0,89]
Major bleeding	3 / 167 (1,8%)	4 / 170 (2,4%)	0,76	[0,17;3,36]	fatal,life threatening, requiring surgical treatment or blood transfusion(intracerebral bleeding included)
Minor bleeding	21 / 167 (12,6%)	42 / 170 (24,7%)	0,51	[0,32;0,82]	overt or occult gastrointestinal tract bleeding, hemoptysis,gross hematuria,nose bleeding,bruising,symptomatic anemia ascribed to bleeding and chronic bleeding with moderate loss of blood
Haemmorhagic stroke	0 / 167 (0,3%)	1 / 170 (0,6%)	0,51	[0,02;15,07]	traumatic intracranial hemorrhage excluded
Cardiovascular death	3 / 167 (1,8%)	5 / 170 (2,9%)	0,61	[0,15;2,52]
Fatal stroke	2 / 167 (1,2%)	0 / 170 (0,3%)	4,07	[0,18;89,64]
TE event or ischemic stroke or systemic embolism	6 / 167 (3,6%)	4 / 170 (2,4%)	1,53	[0,44;5,31]	thrombo-embolic event, ischemic stroke or systemic embolism
intracranial hemorrhage	1 / 167 (0,6%)	2 / 170 (1,2%)	0,51	[0,05;5,56]	traumatic intracranial hemorrhage excluded
Adverse events	0 / 167 (0,3%)	0 / 170 (0,3%)	1,02	[0,02;51,01]
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 3.5 years)
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
thrombo-embolic event (cerebral or systemic)	3,59%	2,35%	1,2%
systemic thrombo-embolic complication	5,99‰	1,18%	-0,58%
stroke (fatal and non fatal)	7,78%	5,88%	1,9%
ischemic stroke	3,59%	2,35%	1,2%
myocardial infarction (fatal and non fatal)	3,59%	2,35%	1,2%
All cause death	3,59%	10,00%	-6,41%
Major bleeding	1,80%	2,35%	-0,56%
Minor bleeding	12,57%	24,71%	-12,13%
Cardiovascular death	1,80%	2,94%	-1,14%
TE event or ischemic stroke or systemic embolism	3,59%	2,35%	1,2%
intracranial hemorrhage	5,99‰	1,18%	-0,58%

Meta-analysis of all similar trials:

antithrombotics in atrial fibrillation for primary prevention of thromboembolic events

Reference(s)

TrialResults-center ID	TRC2619
Trials register #	NA