See also:

RE-LY (150mg) study, 2009	TRC7218
[NCT00262600]	download pdf: dabigatran 150mg | antithrombotics for atrial fibrillation

Treatments

Studied treatment	dabigatran 150 mg twice a day
Control treatment	warfarin adjusted-dose to a 2.0 to 3.0 INR
Remarks	3 arms: dabigatran 110 mg, 150mg and warfarin
Treatments description	time within the therapeutic range (%) 64% mean

Patients

Patients	Patients With Non-Valvular Atrial Fibrillation
Inclusion criteria	Patients with non-valvular atrial fibrillation (AF), at moderate to high risk of stroke, or systemic embolism with at least one additional risk factor (i.e. pre vious ischemic stroke, TIA, or systemic embolism, left ventricular dysfunction, age >=75 years, age >=65 with either diabetes mellitus, history of coronary artery disease or hy pertension)
Baseline characteristics	age(mean) 71.5y  male(%) 63.3%  weight(mean) 82.6 kg  systolic blood pressure(mean) 131.1 mm Hg  diastolic blood pressure(mean) 77 mmHg  hypertension(%) 78.9%  diabete mellitus(%) 23.2%  prior TIA or stroke(%) 20%  prior myocardial infarction(%) 16.5%  paroxysmal AF(%) 33.2%  subgroup test a  CHADS2 Score (mean) 2.1  CHADS2 Score = 2 (%) 36%  CHADS2 Score = 3 (%) 32% (CHADS2>=3)

Method and design

Randomized effectives	6076 / 6022 (studied vs. control)
Design	Parallel groups
Blinding	open (blind assessment)
Follow-up duration	2 y (median)
Lost to follow-up	0.1% (20/18113)
Number of centre	951
Geographic area	44 countries
Hypothesis	Non inferiority
Primary endpoint	stroke or systemic embolism
Withdrawals (T1/T0)	21.2% / 16.6%

Results

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

Endpoint	Events (%)		Relative Risk	95% CI
	Studied treat.	Control treat.
Stroke or systemic embolism	134 / 6076 (2,2%)	199 / 6022 (3,3%)	0,67	[0,54;0,83]
Stroke	122 / 6076 (2,0%)	185 / 6022 (3,1%)	0,65	[0,52;0,82]
Hemorrhagic	12 / 6076 (0,2%)	45 / 6022 (0,7%)	0,26	[0,14;0,50]
Ischemic or unspecified	111 / 6076 (1,8%)	142 / 6022 (2,4%)	0,77	[0,61;0,99]
	Not calculable (data not available)
Nondisabling stroke	44 / 6076 (0,7%)	69 / 6022 (1,1%)	0,63	[0,43;0,92]
Disabling or fatal stroke	80 / 6076 (1,3%)	118 / 6022 (2,0%)	0,67	[0,51;0,89]
Myocardial infarction	89 / 6076 (1,5%)	63 / 6022 (1,0%)	1,40	[1,02;1,93]
Pulmonary embolism	18 / 6076 (0,3%)	11 / 6022 (0,2%)	1,62	[0,77;3,43]
Hospitalization	2430 / 6076 (40,0%)	2458 / 6022 (40,8%)	0,98	[0,94;1,02]
Death from vascular causes	274 / 6076 (4,5%)	317 / 6022 (5,3%)	0,86	[0,73;1,00]
Death from any cause	438 / 6076 (7,2%)	487 / 6022 (8,1%)	0,89	[0,79;1,01]
Major bleeding	375 / 6076 (6,2%)	397 / 6022 (6,6%)	0,94	[0,82;1,07]
Life threatening Major bleeding	175 / 6076 (2,9%)	212 / 6022 (3,5%)	0,82	[0,67;1,00]
Non�life threatening Major bleeding	226 / 6076 (3,7%)	208 / 6022 (3,5%)	1,08	[0,90;1,30]
Gastrointestinal Major bleeding	182 / 6076 (3,0%)	120 / 6022 (2,0%)	1,50	[1,20;1,89]
Minor bleeding	1787 / 6076 (29,4%)	1931 / 6022 (32,1%)	0,92	[0,87;0,97]
Major or minor bleeding	1977 / 6076 (32,5%)	2142 / 6022 (35,6%)	0,91	[0,87;0,96]
Intracranial bleeding	36 / 6076 (0,6%)	87 / 6022 (1,4%)	0,41	[0,28;0,60]
Extracranial bleeding	342 / 6076 (5,6%)	315 / 6022 (5,2%)	1,08	[0,93;1,25]
Net clinical benefit	832 / 6076 (13,7%)	901 / 6022 (15,0%)	0,92	[0,84;1,00]

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]

Coronary event

195 / 12091
75 / 6022
1,29 [0,99;1,69]

thrombo-embolic event (cerebral or systemic)

134 / 6076
199 / 6022
0,67 [0,54;0,83]

systemic thrombo-embolic complication

12 / 6076
14 / 6022
0,85 [0,39;1,84]

stroke (fatal and non fatal)

122 / 6076
185 / 6022
0,65 [0,52;0,82]

ischemic stroke

111 / 6076
142 / 6022
0,77 [0,61;0,99]

myocardial infarction (fatal and non fatal)

89 / 6076
63 / 6022
1,40 [1,02;1,93]

All cause death

438 / 6076
487 / 6022
0,89 [0,79;1,01]

Bleeding

1977 / 6076
2142 / 6022
0,91 [0,87;0,96]

Major bleeding

375 / 6076
397 / 6022
0,94 [0,82;1,07]

Minor bleeding

1787 / 6076
1931 / 6022
0,92 [0,87;0,97]

Haemmorhagic stroke

12 / 6076
45 / 6022
0,26 [0,14;0,50]

Fatal bleeding

175 / 6076
212 / 6022
0,82 [0,67;1,00]

Gastrointestinal major bleeding

182 / 6076
120 / 6022
1,50 [1,20;1,89]

Cardiovascular death

274 / 6076
317 / 6022
0,86 [0,73;1,00]

Fatal stroke

80 / 6076
118 / 6022
0,67 [0,51;0,89]

Non-lifethreatening major bleeding

226 / 6076
208 / 6022
1,08 [0,90;1,30]

Lifethreatening major bleeding

175 / 6076
212 / 6022
0,82 [0,67;1,00]

Non fatal stroke

44 / 6076
69 / 6022
0,63 [0,43;0,92]

intracranial hemorrhage

36 / 6076
87 / 6022
0,41 [0,28;0,60] 0 2 1.0

Relative risks
Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
	Studied treat.	Control treat.
Coronary event	195 / 12091 (1,6%)	75 / 6022 (1,2%)	1,29	[0,99;1,69]		16949
thrombo-embolic event (cerebral or systemic)	134 / 6076 (2,2%)	199 / 6022 (3,3%)	0,67	[0,54;0,83]	Stroke or systemic embolism
systemic thrombo-embolic complication	12 / 6076 (0,2%)	14 / 6022 (0,2%)	0,85	[0,39;1,84]	imputed	11169
stroke (fatal and non fatal)	122 / 6076 (2,0%)	185 / 6022 (3,1%)	0,65	[0,52;0,82]	Stroke
ischemic stroke	111 / 6076 (1,8%)	142 / 6022 (2,4%)	0,77	[0,61;0,99]	Ischemic or unspecified
myocardial infarction (fatal and non fatal)	89 / 6076 (1,5%)	63 / 6022 (1,0%)	1,40	[1,02;1,93]		11169
All cause death	438 / 6076 (7,2%)	487 / 6022 (8,1%)	0,89	[0,79;1,01]	Death from any cause
Bleeding	1977 / 6076 (32,5%)	2142 / 6022 (35,6%)	0,91	[0,87;0,96]	Major or minor bleeding
Major bleeding	375 / 6076 (6,2%)	397 / 6022 (6,6%)	0,94	[0,82;1,07]	Major bleeding
Minor bleeding	1787 / 6076 (29,4%)	1931 / 6022 (32,1%)	0,92	[0,87;0,97]	Minor bleeding
Haemmorhagic stroke	12 / 6076 (0,2%)	45 / 6022 (0,7%)	0,26	[0,14;0,50]	Hemorrhagic
Fatal bleeding	175 / 6076 (2,9%)	212 / 6022 (3,5%)	0,82	[0,67;1,00]	Life threatening Major bleeding
Gastrointestinal major bleeding	182 / 6076 (3,0%)	120 / 6022 (2,0%)	1,50	[1,20;1,89]	Gastrointestinal Major bleeding
Cardiovascular death	274 / 6076 (4,5%)	317 / 6022 (5,3%)	0,86	[0,73;1,00]	Death from vascular causes
Fatal stroke	80 / 6076 (1,3%)	118 / 6022 (2,0%)	0,67	[0,51;0,89]	Disabling or fatal stroke
Non-lifethreatening major bleeding	226 / 6076 (3,7%)	208 / 6022 (3,5%)	1,08	[0,90;1,30]	Non�life threatening Major bleeding
Lifethreatening major bleeding	175 / 6076 (2,9%)	212 / 6022 (3,5%)	0,82	[0,67;1,00]	Life threatening Major bleeding
Non fatal stroke	44 / 6076 (0,7%)	69 / 6022 (1,1%)	0,63	[0,43;0,92]	Nondisabling stroke
intracranial hemorrhage	36 / 6076 (0,6%)	87 / 6022 (1,4%)	0,41	[0,28;0,60]	Intracranial bleeding
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 11169: Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin LDabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med 2009 Sep 17;361:1139-51 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 2 y (median))
Endpoint	Events rate		Absolute risk reduction (ARR)
	Studied treat.	Control treat.
Coronary event	1,61%	1,25%	0,37%
thrombo-embolic event (cerebral or systemic)	2,21%	3,30%	-1,10%
systemic thrombo-embolic complication	1,97‰	2,32‰	-0,03%
stroke (fatal and non fatal)	2,01%	3,07%	-1,06%
ischemic stroke	1,83%	2,36%	-0,53%
myocardial infarction (fatal and non fatal)	1,46%	1,05%	0,42%
All cause death	7,21%	8,09%	-0,88%
Bleeding	32,54%	35,57%	-3,03%
Major bleeding	6,17%	6,59%	-0,42%
Minor bleeding	29,41%	32,07%	-2,65%
Haemmorhagic stroke	1,97‰	7,47‰	-0,55%
Fatal bleeding	2,88%	3,52%	-0,64%
Gastrointestinal major bleeding	3,00%	1,99%	1,0%
Cardiovascular death	4,51%	5,26%	-0,75%
Fatal stroke	1,32%	1,96%	-0,64%
Non-lifethreatening major bleeding	3,72%	3,45%	0,27%
Lifethreatening major bleeding	2,88%	3,52%	-0,64%
Non fatal stroke	7,24‰	1,15%	-0,42%
intracranial hemorrhage	5,92‰	1,44%	-0,85%

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	TRC7218
Trials register #	NCT00262600
Study web site link	,

• Ezekowitz MD, Connolly S, Parekh A, Reilly PA, Varrone J, Wang S, Oldgren J, Themeles E, Wallentin L, Yusuf S. Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran.. Am Heart J 2009;157:805-10, 810.e1-2
  Pubmed | Hubmed | Fulltext
• Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L. Dabigatran versus warfarin in patients with atrial fibrillation.. N Engl J Med 2009 Sep 17;361:1139-51 - 10.1056/NEJMoa0905561
  Pubmed | Hubmed | Fulltext

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