Related trials
ENGAGE-AF TIMI 48 High dose, 2013 - edoxaban vs warfarin standard dose
ARISTOTLE, 2011 - apixaban vs warfarin standard dose
AVERROES, 2011 - apixaban vs aspirin
ROCKET-AF, 2010 - rivaroxaban vs warfarin standard dose
ACTIVE A, 2009 - aspirin + clopidogrel vs aspirin
RE-LY (150mg), 2009 - dabigatran 150mg vs warfarin standard dose
RE-LY (110mg), 2009 - dabigatran 110mg vs warfarin standard dose
Lip (phase 2 AZD0837), 2009 - AZD0837 vs warfarin standard dose
AMADEUS, 2008 - idraparinux vs warfarin standard dose
PETRO (150mg), 2007 - dabigatran 150mg vs warfarin standard dose
ACTIVE W, 2006 - aspirin + clopidogrel vs anticoagulant
Japanese AF Trial, 2006 - aspirin vs control
SPORTIF V, 2005 - ximelagatran vs warfarin standard dose
NASPEAF (triflusal + coumadin medium dose vs coumadin standard dose), 2004 - triflusal+coumadin medium dose vs coumadin standard dose
NASPEAF (triflusal+coumadin medium dose vs triflusal), 2004 - triflusal+coumadin medium dose vs triflusal
NASPEAF (triflusal vs coumadin standard dose)), 2004 - triflusal vs coumadin standard dose
SAFT(warfarin low dose + aspirin vs no treatment), 2003 - warfarin low dose + aspirin vs control
SPORTIF III, 2003 - ximelagatran vs warfarin standard dose
SPORTIF II (ximelagatran vs warfarin standard dose), 2002 - ximelagatran vs warfarin standard dose
PATAF (coumadin low dose vs coumadin standard dose), 1999 - coumadin low dose vs coumadin standard dose
PATAF (vs coumadin standard dose), 1999 - aspirin vs coumadin standard dose
LASAF(aspirin vs no treatment), 1999 - aspirin vs control
PATAF (vs coumadin low dose), 1999 - aspirin vs coumadin low dose
AFASAK II (aspirin vs warfarin low dose), 1998 - aspirin vs warfarin low dose
AFASAK II (warfarin low dose+aspirin vs warfarin standard dose), 1998 - warfarin + aspirin vs warfarin standard dose
See also:
All atrial fibrillation clinical trials
All clinical trials of new oral anticoagulants
All clinical trials of rivaroxaban
|
|
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
|