See also:

SPORTIF V study, 2005	TRC2638
	download pdf: ximelagatran | antithrombotics for atrial fibrillation

Treatments

Studied treatment	ximelegatran 36 mg twice daily
Control treatment	warfarin standard dose(target INR 2-3)
Concomittant treatment	-aspirin < 100 mg -other antithrombotic agents are prohibited within 10 days of randomisation and during the treatment phase. -NSAIDs are authorized up to 7 days per month -COX-2 inhibitors are permitted ad lib. -concomitant therapies are at the discretion of the treating physician (anticoagulants and antiplatelet agents excepted).
Treatments description	INR obtained(mean) 2.4

Patients

Patients	One or more stroke risk factor in addition to atrial fibrillation.High risk patients with non valvular atrial fibrillation.
Inclusion criteria	Age >18,Persistent or paroxysmal AF verified by at least 2 ECG,One or more stroke risk factors in addition to AF(hypertension,age>75,previous stroke TIA or systemic embolism,left ventricular dysfunction,age>65+coronary artery disease,age >65+diabete mellitus)
Exclusion criteria	Mitral stenosis,Transient AF caused by reversible disorder,Stroke within the previous 30 days or TIA within 3 days,Condition associated with increased risk of bleeding,Active infective endocarditis,Current atrial myxoma or left ventricular thrombus,Admission for acute coronary syndrome or percutaeous coronary intervention within 30 days,Requirement for chronic anticoagulation treatment for disorders other than AF,planned cardioversion,Planned major surgery,treatment with platelet inhibitor drugs other than aspirin 100mg/day or less within 10 days or fibrinolytic agents within 30 days before randomisation,Regular use of NSAI drugs,Renal insuffiency,Active liver disease or persistent elevationof liver enzymes,Childbearing potential,pregnancy or lactation,Drug addiction alcohol abuse or both,Anaemia or thrombopenia
Baseline characteristics	age(mean) 72  male(%) 69  hypertension(%) 81  diabete mellitus(%) 25  prior TIA or stroke(%) 18  left ventricular dysfunction(%) 39  paroxysmal AF(%) 14  current smoker(%) 7  subgroup test a

Method and design

Randomized effectives	1960 / 1962 (studied vs. control)
Design	Parallel groups
Blinding	Double blind
Follow-up duration	20 months
Lost to follow-up	0.58% lost to follow up
Number of centre	409
Geographic area	north america
Primary endpoint	All stroke and systemic embolism
Withdrawals (T1/T0)	37% / 33%

Results

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

Coronary event

26 / 1960
37 / 1962
0,70 [0,43;1,16]

thrombo-embolic event (cerebral or systemic)

51 / 1960
37 / 1962
classic 1,38 [0,91;2,10]

systemic thrombo-embolic complication

6 / 1960
1 / 1962
classic 6,01 [0,72;49,84]

stroke (fatal and non fatal)

47 / 1960
38 / 1962
1,24 [0,81;1,89]

ischemic stroke

45 / 1960
36 / 1962
1,25 [0,81;1,93]

myocardial infarction (fatal and non fatal)

26 / 1960
37 / 1962
0,70 [0,43;1,16]

All cause death

116 / 1960
123 / 1962
0,94 [0,74;1,21]

Bleeding

737 / 1960
903 / 1962
0,82 [0,76;0,88]

Major bleeding

63 / 1960
84 / 1962
0,75 [0,54;1,03]

Haemmorhagic stroke

2 / 1960
2 / 1962
classic 1,00 [0,14;7,10]

Fatal stroke

10 / 1960
3 / 1962
classic 3,34 [0,92;12,11]

TE event or ischemic stroke or systemic embolism

45 / 1960
36 / 1962
1,25 [0,81;1,93]

hypertransaminasemia

117 / 1960
15 / 1962
classic 7,81 [4,58;13,32]

Adverse events

1827 / 1960
1834 / 1962
1,00 [0,98;1,01] 0 2 1.0

Relative risks
Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
	Studied treat.	Control treat.
Coronary event	26 / 1960 (1,3%)	37 / 1962 (1,9%)	0,70	[0,43;1,16]		16949
thrombo-embolic event (cerebral or systemic)	51 / 1960 (2,6%)	37 / 1962 (1,9%)	1,38	[0,91;2,10]		1855
systemic thrombo-embolic complication	6 / 1960 (0,3%)	1 / 1962 (0,1%)	6,01	[0,72;49,84]	abrupt vascular insufficiency asociated with clinical and radiological evidence of arterial occlusion in the absence of another likely mechanism
stroke (fatal and non fatal)	47 / 1960 (2,4%)	38 / 1962 (1,9%)	1,24	[0,81;1,89]	abrupt onset of a focal neurological deficit in the distribution of a brain artery persisting more than 24 hours or due to intracerebral hemorrhage
ischemic stroke	45 / 1960 (2,3%)	36 / 1962 (1,8%)	1,25	[0,81;1,93]
myocardial infarction (fatal and non fatal)	26 / 1960 (1,3%)	37 / 1962 (1,9%)	0,70	[0,43;1,16]	MI	1855
All cause death	116 / 1960 (5,9%)	123 / 1962 (6,3%)	0,94	[0,74;1,21]
Bleeding	737 / 1960 (37,6%)	903 / 1962 (46,0%)	0,82	[0,76;0,88]	major and minir bleeding	1855
Major bleeding	63 / 1960 (3,2%)	84 / 1962 (4,3%)	0,75	[0,54;1,03]	bleeding that was fatal or clinically overt and associated with either transfusion of 2 units of blood or a 20g/l decrease in Hb or bleeding that was intracranial,retroperitoneal,spinal,ocular,pericardial or atraumatic articular but not intracerebral
Haemmorhagic stroke	2 / 1960 (0,1%)	2 / 1962 (0,1%)	1,00	[0,14;7,10]
Fatal stroke	10 / 1960 (0,5%)	3 / 1962 (0,2%)	3,34	[0,92;12,11]	death from any cause within 30 days of stroke
TE event or ischemic stroke or systemic embolism	45 / 1960 (2,3%)	36 / 1962 (1,8%)	1,25	[0,81;1,93]	thrombo-embolic event, ischemic stroke or systemic embolism
hypertransaminasemia	117 / 1960 (6,0%)	15 / 1962 (0,8%)	7,81	[4,58;13,32]	serum alanine-aminotransferase concentration higher than 3 times the upper limit of normal
Adverse events	1827 / 1960 (93,2%)	1834 / 1962 (93,5%)	1,00	[0,98;1,01]	purpura,dizziness,diarrhea,edema,fatigue,epistaxis, chest pain, hypertransaminasemia, hematuria
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 1855: Albers GW, Diener HC, Frison L, Grind M, Nevinson M, Partridge S, Halperin JL, Horrow J, Olsson SB, Petersen P, Vahanian AXimelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial.JAMA 2005 Feb 9;293:690-8 16949: Mak KHCoronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials.BMJ Open 2012;2:

Endpoint	studied treat.	control treat.	mean diff

Absolute risk reduction (for a follow-up of 20 months)
Endpoint	Events rate		Absolute risk reduction (ARR)
	Studied treat.	Control treat.
Coronary event	1,33%	1,89%	-0,56%
thrombo-embolic event (cerebral or systemic)	2,60%	1,89%	0,72%
systemic thrombo-embolic complication	3,06‰	0,51‰	0,26%
stroke (fatal and non fatal)	2,40%	1,94%	0,46%
ischemic stroke	2,30%	1,83%	0,46%
myocardial infarction (fatal and non fatal)	1,33%	1,89%	-0,56%
All cause death	5,92%	6,27%	-0,35%
Bleeding	37,60%	46,02%	-8,42%
Major bleeding	3,21%	4,28%	-1,07%
Haemmorhagic stroke	1,02‰	1,02‰	0,00%
Fatal stroke	5,10‰	1,53‰	0,36%
TE event or ischemic stroke or systemic embolism	2,30%	1,83%	0,46%
hypertransaminasemia	5,97%	7,65‰	5,2%
Adverse events	93,21%	93,48%	-0,26%

Meta-analysis of all similar trials:

antithrombotics in atrial fibrillation for primary prevention of thromboembolic events

direct antithrombins in atrial fibrillation for all type of patients

new oral anticoagulants in atrial fibrillation for all type of patients

Reference(s)

TrialResults-center ID	TRC2638
Trials register #	NA

• Halperin JL. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V).. Am Heart J 2003 Sep;146:431-8
  Pubmed | Hubmed | Fulltext
• Albers GW, Diener HC, Frison L, Grind M, Nevinson M, Partridge S, Halperin JL, Horrow J, Olsson SB, Petersen P, Vahanian A. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial.. JAMA 2005 Feb 9;293:690-8
  Pubmed | Hubmed | Fulltext

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