See also:

RE-LY (110mg) study, 2009	TRC9892
[NCT00262600]	download pdf: dabigatran 110mg | antithrombotics for atrial fibrillation

Treatments

Studied treatment	dabigatran 110 mg twice a day
Control treatment	warfarin adjusted dose to a 2-3 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

Method and design

Randomized effectives	6015 / 6022 (studied vs. control)
Design	Parallel groups
Blinding	open (blind assessment)
Follow-up duration	2 y (median)
Number of centre	951
Geographic area	44 countries
Hypothesis	Non inferiority
Primary endpoint	stroke or systemic embolism
Remarks

Remarks / Comments

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	182 / 6015 (3,0%)	199 / 6022 (3,3%)	0,92	[0,75;1,12]
Stroke	171 / 6015 (2,8%)	185 / 6022 (3,1%)	0,93	[0,75;1,14]
Hemorrhagic Stroke	14 / 6015 (0,2%)	45 / 6022 (0,7%)	0,31	[0,17;0,57]
Ischemic or unspecified stroke	159 / 6015 (2,6%)	142 / 6022 (2,4%)	1,12	[0,90;1,40]
Nondisabling stroke	60 / 6015 (1,0%)	69 / 6022 (1,1%)	0,87	[0,62;1,23]
Disabling or fatal stroke	112 / 6015 (1,9%)	118 / 6022 (2,0%)	0,95	[0,74;1,23]
Myocardial infarction	86 / 6015 (1,4%)	63 / 6022 (1,0%)	1,37	[0,99;1,89]
Pulmonary embolism	14 / 6015 (0,2%)	11 / 6022 (0,2%)	1,27	[0,58;2,80]
Hospitalization	2311 / 6015 (38,4%)	2458 / 6022 (40,8%)	0,94	[0,90;0,98]
Death from vascular causes	289 / 6015 (4,8%)	317 / 6022 (5,3%)	0,91	[0,78;1,07]
Death from any cause	446 / 6015 (7,4%)	487 / 6022 (8,1%)	0,92	[0,81;1,04]
Major bleeding	322 / 6015 (5,4%)	397 / 6022 (6,6%)	0,81	[0,70;0,94]
Life threatening Major bleeding	145 / 6015 (2,4%)	212 / 6022 (3,5%)	0,68	[0,56;0,84]
Non�life threatening Major bleeding	198 / 6015 (3,3%)	208 / 6022 (3,5%)	0,95	[0,79;1,15]
Gastrointestinal Major bleeding	133 / 6015 (2,2%)	120 / 6022 (2,0%)	1,11	[0,87;1,42]
Minor bleeding	1566 / 6015 (26,0%)	1931 / 6022 (32,1%)	0,81	[0,77;0,86]
Major or minor bleeding	1740 / 6015 (28,9%)	2142 / 6022 (35,6%)	0,81	[0,77;0,86]
Intracranial bleeding	27 / 6015 (0,4%)	87 / 6022 (1,4%)	0,31	[0,20;0,48]
Extracranial bleeding	299 / 6015 (5,0%)	315 / 6022 (5,2%)	0,95	[0,81;1,11]
Net clinical benefit	844 / 6015 (14,0%)	901 / 6022 (15,0%)	0,94	[0,86;1,02]

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)

182 / 6015
199 / 6022
0,92 [0,75;1,12]

systemic thrombo-embolic complication

11 / 6015
14 / 6022
0,79 [0,36;1,73]

stroke (fatal and non fatal)

171 / 6015
185 / 6022
0,93 [0,75;1,14]

ischemic stroke

159 / 6015
142 / 6022
1,12 [0,90;1,40]

myocardial infarction (fatal and non fatal)

86 / 6015
63 / 6022
1,37 [0,99;1,89]

All cause death

446 / 6015
487 / 6022
0,92 [0,81;1,04]

Bleeding

1740 / 6015
2142 / 6022
0,81 [0,77;0,86]

Major bleeding

322 / 6015
397 / 6022
0,81 [0,70;0,94]

Minor bleeding

1566 / 6015
1931 / 6022
0,81 [0,77;0,86]

Haemmorhagic stroke

14 / 6015
45 / 6022
0,31 [0,17;0,57]

Gastrointestinal major bleeding

133 / 6015
120 / 6022
1,11 [0,87;1,42]

Cardiovascular death

289 / 6015
317 / 6022
0,91 [0,78;1,07]

Fatal stroke

112 / 6015
118 / 6022
0,95 [0,74;1,23]

Non-lifethreatening major bleeding

198 / 6015
208 / 6022
0,95 [0,79;1,15]

Lifethreatening major bleeding

145 / 6015
212 / 6022
0,68 [0,56;0,84]

TE event or ischemic stroke or systemic embolism

182 / 6015
199 / 6022
0,92 [0,75;1,12]

Non fatal stroke

60 / 6015
69 / 6022
0,87 [0,62;1,23]

intracranial hemorrhage

27 / 6015
87 / 6022
0,31 [0,20;0,48] 0 2 1.0

Relative risks
Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
	Studied treat.	Control treat.
thrombo-embolic event (cerebral or systemic)	182 / 6015 (3,0%)	199 / 6022 (3,3%)	0,92	[0,75;1,12]	Stroke or systemic embolism
systemic thrombo-embolic complication	11 / 6015 (0,2%)	14 / 6022 (0,2%)	0,79	[0,36;1,73]	imputed	11171
stroke (fatal and non fatal)	171 / 6015 (2,8%)	185 / 6022 (3,1%)	0,93	[0,75;1,14]	Stroke
ischemic stroke	159 / 6015 (2,6%)	142 / 6022 (2,4%)	1,12	[0,90;1,40]	Ischemic or unspecified stroke
myocardial infarction (fatal and non fatal)	86 / 6015 (1,4%)	63 / 6022 (1,0%)	1,37	[0,99;1,89]	Myocardial infarction
All cause death	446 / 6015 (7,4%)	487 / 6022 (8,1%)	0,92	[0,81;1,04]	Death from any cause
Bleeding	1740 / 6015 (28,9%)	2142 / 6022 (35,6%)	0,81	[0,77;0,86]	Major or minor bleeding
Major bleeding	322 / 6015 (5,4%)	397 / 6022 (6,6%)	0,81	[0,70;0,94]	Major bleeding
Minor bleeding	1566 / 6015 (26,0%)	1931 / 6022 (32,1%)	0,81	[0,77;0,86]	Minor bleeding
Haemmorhagic stroke	14 / 6015 (0,2%)	45 / 6022 (0,7%)	0,31	[0,17;0,57]	Hemorrhagic Stroke
Gastrointestinal major bleeding	133 / 6015 (2,2%)	120 / 6022 (2,0%)	1,11	[0,87;1,42]	Gastrointestinal Major bleeding
Cardiovascular death	289 / 6015 (4,8%)	317 / 6022 (5,3%)	0,91	[0,78;1,07]	Death from vascular causes
Fatal stroke	112 / 6015 (1,9%)	118 / 6022 (2,0%)	0,95	[0,74;1,23]	Disabling or fatal stroke
Non-lifethreatening major bleeding	198 / 6015 (3,3%)	208 / 6022 (3,5%)	0,95	[0,79;1,15]	Non�life threatening Major bleeding
Lifethreatening major bleeding	145 / 6015 (2,4%)	212 / 6022 (3,5%)	0,68	[0,56;0,84]	Life threatening Major bleeding
TE event or ischemic stroke or systemic embolism	182 / 6015 (3,0%)	199 / 6022 (3,3%)	0,92	[0,75;1,12]	Stroke or systemic embolism
Non fatal stroke	60 / 6015 (1,0%)	69 / 6022 (1,1%)	0,87	[0,62;1,23]	Nondisabling stroke
intracranial hemorrhage	27 / 6015 (0,4%)	87 / 6022 (1,4%)	0,31	[0,20;0,48]	Intracranial bleeding
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 11171: 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 Aug 30;: 0:

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.
thrombo-embolic event (cerebral or systemic)	3,03%	3,30%	-0,28%
systemic thrombo-embolic complication	1,83‰	2,32‰	-0,05%
stroke (fatal and non fatal)	2,84%	3,07%	-0,23%
ischemic stroke	2,64%	2,36%	0,29%
myocardial infarction (fatal and non fatal)	1,43%	1,05%	0,38%
All cause death	7,41%	8,09%	-0,67%
Bleeding	28,93%	35,57%	-6,64%
Major bleeding	5,35%	6,59%	-1,24%
Minor bleeding	26,03%	32,07%	-6,03%
Haemmorhagic stroke	2,33‰	7,47‰	-0,51%
Gastrointestinal major bleeding	2,21%	1,99%	0,22%
Cardiovascular death	4,80%	5,26%	-0,46%
Fatal stroke	1,86%	1,96%	-0,10%
Non-lifethreatening major bleeding	3,29%	3,45%	-0,16%
Lifethreatening major bleeding	2,41%	3,52%	-1,11%
TE event or ischemic stroke or systemic embolism	3,03%	3,30%	-0,28%
Non fatal stroke	9,98‰	1,15%	-0,15%
intracranial hemorrhage	4,49‰	1,44%	-1,00%

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	TRC9892
Trials register #	NCT00262600

• Ezekowitz MD, Connolly S, Parekh A, Reilly PA, Varrone J, Wang S, Oldgren J, Themeles E, Wallentin L, Yusuf S. . 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 Aug 30;: - 10.1056.NEJM0a0905561
  Pubmed | Hubmed | Fulltext

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