See also:

ROCKET-AF study, 2010	TRC7222
[NCT00403767]	download pdf: rivaroxaban | antithrombotics for atrial fibrillation

Treatments

Studied treatment	Rivaroxaban 20mg p.o. once daily (15 mg for Creatinine Cl 30-49 ml/min)
Control treatment	Warfarin p.o. once daily titrated to a target INR of 2.5 (range 2.0 to 3.0, inclusive)
Treatments description	time within the therapeutic range (%) 55% (median 58%)

Patients

Patients	Subjects With Non-Valvular Atrial Fibrillation
Inclusion criteria	Male and female patients 18 years of age or older; Subjects must have documented atrial fibrillation on 2 separate occasions within 6 months before screening ; History of a prior stroke, transient ischemic attack or non-neurologic systemic embolism believed to be cardiac in origin, OR at least two of the following risk factors: Heart failure , Hypertension, Age 75 years or greater , Diabetes mellitus
Exclusion criteria	Significant mitral stenosis;Transient atrial fibrillation caused by a reversible disorder ;Active internal bleeding ; Severe disabling stroke ; History of intracranial bleeding Hemorrhagic disorders
Baseline characteristics	age(mean) 73y  male(%) 60%  hypertension(%) 90.5%  diabete mellitus(%) 39.5%  prior TIA or stroke(%) 55% (stroke,TIA, embolism)  prior myocardial infarction(%) 17.5%  subgroup test b  CHADS2 Score (mean) 3.47  CHADS2 Score = 2 (%) 13%  CHADS2 Score = 3 (%) 43.5%

Method and design

Randomized effectives	7131 / 7133 (studied vs. control)
Design	Parallel groups
Blinding	double blind
Follow-up duration	median 1.94 y
Lost to follow-up	0.22% (32)
Number of centre	1178
Geographic area	45 countries
Hypothesis	Non inferiority
Primary endpoint	stroke or non-CNS systemic embolism
Withdrawals (T1/T0)	23.7% / 22.2%

Results

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

Coronary event

101 / 7111
126 / 7125
0,80 [0,62;1,04]

thrombo-embolic event (cerebral or systemic)

269 / 7081
306 / 7090
0,88 [0,75;1,03]

systemic thrombo-embolic complication

NA / 7131
NA / 7133
0,74 [0,42;1,31]

stroke (fatal and non fatal)

184 / 7061
221 / 7082
0,84 [0,69;1,01]

ischemic stroke

149 / 7061
161 / 7082
0,93 [0,74;1,16]

myocardial infarction (fatal and non fatal)

101 / 7061
126 / 7082
0,80 [0,62;1,04]

All cause death

208 / 7061
250 / 7082
0,83 [0,70;1,00]

Major bleeding

395 / 7111
386 / 7125
1,03 [0,89;1,18]

Haemmorhagic stroke

29 / 7061
50 / 7082
0,58 [0,37;0,92]

Fatal bleeding

27 / 7111
55 / 7125
0,49 [0,31;0,78]

Gastrointestinal major bleeding

224 / 7111
154 / 7125
1,46 [1,19;1,78]

major or clinically relevant non-major bleeding

1475 / 7111
1449 / 7125
1,02 [0,96;1,09]

Cardiovascular death

170 / 7061
193 / 7082
0,88 [0,72;1,08]

Fatal stroke

47 / 7061
67 / 7082
0,70 [0,49;1,02]

Lifethreatening major bleeding

91 / 7111
133 / 7125
0,69 [0,53;0,89]

intracranial hemorrhage

55 / 7111
84 / 7125
0,66 [0,47;0,92] 0 2 1.0

Relative risks
Endpoint	Events (%)		Relative Risk	95% CI	Endpoint definition in the trial	Ref
	Studied treat.	Control treat.
Coronary event	101 / 7111 (1,4%)	126 / 7125 (1,8%)	0,80	[0,62;1,04]		16949
thrombo-embolic event (cerebral or systemic)	269 / 7081 (3,8%)	306 / 7090 (4,3%)	0,88	[0,75;1,03]	ITT n=14171	14871
systemic thrombo-embolic complication	NA / 7131	NA / 7133	0,74	[0,42;1,31]	Non-CNS Embolism
stroke (fatal and non fatal)	184 / 7061 (2,6%)	221 / 7082 (3,1%)	0,84	[0,69;1,01]	Safety, as-treated population	14871
ischemic stroke	149 / 7061 (2,1%)	161 / 7082 (2,3%)	0,93	[0,74;1,16]	Safety, as-treated population	14871
myocardial infarction (fatal and non fatal)	101 / 7061 (1,4%)	126 / 7082 (1,8%)	0,80	[0,62;1,04]	Safety, as-treated population	14871
All cause death	208 / 7061 (2,9%)	250 / 7082 (3,5%)	0,83	[0,70;1,00]	Safety, as-treated population	14871
Major bleeding	395 / 7111 (5,6%)	386 / 7125 (5,4%)	1,03	[0,89;1,18]		14871
Haemmorhagic stroke	29 / 7061 (0,4%)	50 / 7082 (0,7%)	0,58	[0,37;0,92]	Hemorrhagic stroke, Safety, as-treated population	14871
Fatal bleeding	27 / 7111 (0,4%)	55 / 7125 (0,8%)	0,49	[0,31;0,78]	Bleeding causing death	14871
Gastrointestinal major bleeding	224 / 7111 (3,2%)	154 / 7125 (2,2%)	1,46	[1,19;1,78]		14871
major or clinically relevant non-major bleeding	1475 / 7111 (20,7%)	1449 / 7125 (20,3%)	1,02	[0,96;1,09]		14871
Cardiovascular death	170 / 7061 (2,4%)	193 / 7082 (2,7%)	0,88	[0,72;1,08]	Safety, as-treated population	14871
Fatal stroke	47 / 7061 (0,7%)	67 / 7082 (0,9%)	0,70	[0,49;1,02]	Safety, as-treated population	14871
Lifethreatening major bleeding	91 / 7111 (1,3%)	133 / 7125 (1,9%)	0,69	[0,53;0,89]	critical bleeding	14871
intracranial hemorrhage	55 / 7111 (0,8%)	84 / 7125 (1,2%)	0,66	[0,47;0,92]		14871
The primary endpoint (if exists) appears in blod characters
Reference(s) used for data extraction: 14871: Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RMRivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation.N Engl J Med 2011 Aug 10;: 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 median 1.94 y)
Endpoint	Events rate		Absolute risk reduction (ARR)
	Studied treat.	Control treat.
Coronary event	1,42%	1,77%	-0,35%
thrombo-embolic event (cerebral or systemic)	3,80%	4,32%	-0,52%
stroke (fatal and non fatal)	2,61%	3,12%	-0,51%
ischemic stroke	2,11%	2,27%	-0,16%
myocardial infarction (fatal and non fatal)	1,43%	1,78%	-0,35%
All cause death	2,95%	3,53%	-0,58%
Major bleeding	5,55%	5,42%	0,14%
Haemmorhagic stroke	4,11‰	7,06‰	-0,30%
Fatal bleeding	3,80‰	7,72‰	-0,39%
Gastrointestinal major bleeding	3,15%	2,16%	0,99%
major or clinically relevant non-major bleeding	20,74%	20,34%	0,41%
Cardiovascular death	2,41%	2,73%	-0,32%
Fatal stroke	6,66‰	9,46‰	-0,28%
Lifethreatening major bleeding	1,28%	1,87%	-0,59%
intracranial hemorrhage	7,73‰	1,18%	-0,41%

Meta-analysis of all similar trials:

antithrombotics in atrial fibrillation for primary prevention of thromboembolic events

direct factor Xa inhibitors in atrial fibrillation for all type of patients

new oral anticoagulants in atrial fibrillation for all type of patients

Reference(s)

TrialResults-center ID	TRC7222
Trials register #	NCT00403767
Study web site link	,

• . Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study.. Am Heart J 2010;159:340-347.e1 - 10.1016/j.ahj.2009.11.025
  Pubmed | Hubmed | Fulltext
• Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation.. N Engl J Med 2011 Aug 10;: - 10.1056/NEJMoa1009638
  Pubmed | Hubmed | Fulltext

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