NASPEAF (triflusal+coumadin medium dose vs triflusal) Trial

NASPEAF (triflusal+coumadin medium dose vs triflusal) study, 2004	TRC2653
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Treatments

Studied treatment

Triflusal 600 mg/d + coumadin medium dose (target INR 1.25-2)
The antiplatelet agent used was triflusal (Grupo Uriach,Spain), a drug structurally related to acetylsalicylic acid ,of which clinical trials showed that 600 mg/day has similar biologic effects and clinical efficacy to aspirin 300 mg/day with fewer bleeding complications. The anticoagulant used was acenocoumarol (Novartis Farmaceutica,Spain), the coumarin derivative most used in several European countries.

Control treatment

Triflusal 600 mg/d
The antiplatelet agent used was triflusal (Grupo Uriach,Spain), a drug structurally related to acetylsalicylic acid ,of which clinical trials showed that 600 mg/day has similar biologic effects and clinical efficacy to aspirin 300 mg/day with fewer bleeding complications.

Patients

Non valvular atrial fibrillation. Intermediate risk patients

Inclusion criteria

Eligible patients were divided in two groups: the high-risk group included nonvalvular plus prior embolism and patients with mitral stenosis with and without prior embolism. All others were included in the intermediate-risk group.

Exclusion criteria

Patients at low risk according to Stroke Prevention in Atrial Fibrillation (SPAF) III stratification or younger than 60 years of age were not included.Exclusion criteria were mechanical valve prosthesis, stroke in the previous six months, serum creatinine over 3 mg/dl, alcoholism or drug addiction, severe uncontrolled hypertension, diffuse arteriosclerosis, and indication for non-steroidal anti-inflammatory drugs or indication/contraindication for antiplatelet or anticoagulant therapy.

Baseline characteristics

age(mean)	69.88
male(%)	57.2
systolic blood pressure(mean)	137.01
diastolic blood pressure(mean)	79.51
hypertension(%)	43.93
diabete mellitus(%)	15.87
paroxysmal AF(%)	8.42
left atrial dimension(mean in mm)	46.59
heart failure(%)	10.86
current smoker(%)	38.78
subgroup test	c

Method and design

Randomized effectives	235 / 242 (studied vs. control)
Design	Parallel groups
Blinding	Open
Follow-up duration	2.76 years
Lost to follow-up	4.19%
Number of centre	13
Geographic area	Spain
Hypothesis	superiority
Primary endpoint	vascular death,TIA,nonfatal stroke or systemic embolism
Remarks	Withdrawals from study treatments are not reported separetely:9% were withdrawn for adverse events without significant difference among groups,9.3% were withdrawn secondary to gp or patient's decision.
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)

3 / 222
15 / 235
0,21 [0,06;0,72]

systemic thrombo-embolic complication

0 / 222
1 / 235
classic 0,21 [0,00;15,45]

stroke (fatal and non fatal)

3 / 222
11 / 235
0,29 [0,08;1,02]

myocardial infarction (fatal and non fatal)

0 / 222
1 / 235
classic 0,21 [0,00;15,45]

All cause death

6 / 222
15 / 235
0,42 [0,17;1,07]

Major bleeding

5 / 222
2 / 235
classic 2,65 [0,52;13,50]

Minor bleeding

16 / 222
5 / 235
classic 3,39 [1,26;9,09]

Haemmorhagic stroke

1 / 222
2 / 235
classic 0,53 [0,05;5,80]

Fatal bleeding

1 / 222
0 / 235
classic 5,29 [0,07;386,28]

Cardiovascular death

2 / 222
8 / 235
0,26 [0,06;1,23]

Fatal stroke

0 / 222
1 / 235
classic 0,21 [0,00;15,45]

TE event or ischemic stroke or systemic embolism

3 / 222
15 / 235
0,21 [0,06;0,72]

Non fatal stroke

3 / 222
10 / 235
0,32 [0,09;1,14]

intracranial hemorrhage

1 / 222
2 / 235
classic 0,53 [0,05;5,80] 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)	3 / 222 (1,4%)	15 / 235 (6,4%)	0,21	[0,06;0,72]
systemic thrombo-embolic complication	0 / 222 (0,2%)	1 / 235 (0,4%)	0,53	[0,02;15,70]	abrupt vascular insufficiency without previous clinical symptoms
stroke (fatal and non fatal)	3 / 222 (1,4%)	11 / 235 (4,7%)	0,29	[0,08;1,02]	focal neurologic deficit lasting more than 24 hours,the ischemic or hemorrhagic etiology was defined by neuroimaging
myocardial infarction (fatal and non fatal)	0 / 222 (0,2%)	1 / 235 (0,4%)	0,53	[0,02;15,70]
All cause death	6 / 222 (2,7%)	15 / 235 (6,4%)	0,42	[0,17;1,07]
Major bleeding	5 / 222 (2,3%)	2 / 235 (0,9%)	2,65	[0,52;13,50]	bleeding requiring hospital admission, blood transfusion or surgery (intracranial and intracerebral bleeding included)
Minor bleeding	16 / 222 (7,2%)	5 / 235 (2,1%)	3,39	[1,26;9,09]
Haemmorhagic stroke	1 / 222 (0,5%)	2 / 235 (0,9%)	0,53	[0,05;5,80]
Fatal bleeding	1 / 222 (0,5%)	0 / 235 (0,2%)	2,12	[0,07;62,80]
Cardiovascular death	2 / 222 (0,9%)	8 / 235 (3,4%)	0,26	[0,06;1,23]	either sudden or any other death occuring within 30 days after a vascular event or progressive heart failure
Fatal stroke	0 / 222 (0,2%)	1 / 235 (0,4%)	0,53	[0,02;15,70]
TE event or ischemic stroke or systemic embolism	3 / 222 (1,4%)	15 / 235 (6,4%)	0,21	[0,06;0,72]	thrombo-embolic event, ischemic stroke or systemic embolism
Non fatal stroke	3 / 222 (1,4%)	10 / 235 (4,3%)	0,32	[0,09;1,14]
intracranial hemorrhage	1 / 222 (0,5%)	2 / 235 (0,9%)	0,53	[0,05;5,80]
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 2.76 years)
Endpoint	Studied treat.	Control treat.	Absolute risk reduction (ARR)
thrombo-embolic event (cerebral or systemic)	1,35%	6,38%	-5,03%
stroke (fatal and non fatal)	1,35%	4,68%	-3,33%
All cause death	2,70%	6,38%	-3,68%
Major bleeding	2,25%	8,51‰	1,4%
Minor bleeding	7,21%	2,13%	5,1%
Haemmorhagic stroke	4,50‰	8,51‰	-0,40%
Cardiovascular death	9,01‰	3,40%	-2,50%
TE event or ischemic stroke or systemic embolism	1,35%	6,38%	-5,03%
Non fatal stroke	1,35%	4,26%	-2,90%
intracranial hemorrhage	4,50‰	8,51‰	-0,40%

Meta-analysis of all similar trials:

antithrombotics in atrial fibrillation for primary prevention of thromboembolic events

Reference(s)

TrialResults-center ID	TRC2653
Trials register #	NA