Recent ACS: STEMI, NSTEMI, UAStabilized 1-7 Days Post-Index Event
Exclusions: increased bleeding risk, warfarin use, ICH, prior stroke if on ASA + thienopyridine
PRIMARY ENDPOINTS:EFFICACY: CV Death, MI, Stroke (Ischemic, Hemorrhagic, or Uncertain Origin)
SAFETY: TIMI major bleeding not associated with CABG
Rivaroxaban5.0 mg BID
n=5,176
Stratified by Thienopyridine Use at MD Discretion
ASA 75 to 100 mg/day
Placebon=5,176
Rivaroxaban 2.5 mg BID
n=5,174
Event driven trial with 1,002 primary efficacy events
Mega et al, N Engl J Med. 2011 Nov 13
ATLAS ACS 2: Design
Placebo Rivaroxaban2.5 mg BID
Rivaroxaban5.0 mg BID
Age, mean (SD) 61.5 (± 9.4) 61.8 (± 9.2) 61.9 (± 9.0)
Sex, male (%) 75.0 74.9 74.2
Prior MI, (%) 27.3 26.3 27.1
Diabetes, (%) 31.8 32.3 31.8
STEMI, (%) 50.9 50.3 49.9
NSTEMI, (%) 25.6 25.5 25.8
UA, (%) 23.6 24.2 24.3
Revasc at Index, (%) 60.7 60.4 60.4
ASA+Thienopyridine, (%) 93.1 93.3 93.3
PRE
HO
SPIT
ALH
OSP
ITAL
ATLAS ACS 2: Baseline Characteristics
Mega et al, N Engl J Med. 2011 Nov 13
Maanden na randomisatie
Rivaroxaban(beide doseringen)
HR 0.84 (0.74-0.96)
mITT p = 0.008ITT p = 0.002
ARR 1.8%NNT = 56
10.7%
8.9%
Ges
chatt
e cu
mul
atiev
e in
cide
ntie
(%)
Placebo
5113 4307 3470 2664 1831 1079 421
10229 8502 6753 5137 3554 2084 831
PlaceboRivaroxaban
2 Yr KM Estimate
No. at Risk
ATLAS ACS 2: Primair Eindpunt
Mega et al, N Engl J Med. 2011 Nov 13
Months After Randomization
Rivaroxaban(both doses)
HR 0.69 (0.51- 0.93)
mITT p = 0.016
ITT p = 0.008
2.9%
2.3%
Esti
mat
ed C
umul
ative
Inci
denc
e (%
)
Placebo
2 Yr KM Estimate
ARC Definite/probable: HR=0.65, mITT p=0.017, ITT p=0.012
ATLAS ACS 2: Stent Thrombosis ARC Definite / Probable / Possible
Mega et al, N Engl J Med. 2011 Nov 13
0
5
10
1 Months
Estim
ated
Cum
ulati
ve In
cide
nce
(%)
Placebo
Rivaroxaban5 mg BID
0
8.8%
10.7%
24
Cardiovascular DeathCV Death / MI / Stroke
HR 0.94
mITTp=0.63
ITTp=0.57
Months0 24
4.0%
4.1%Placebo
Rivaroxaban5 mg BID
HR 0.85
mITTp=0.028
ITTp=0.010
NNT=53
Mega et al, N Engl J Med. 2011 Nov 13
ATLAS ACS 2: Efficacy endpointsDose 5.0 mg BID
0 24
Rivaroxaban2.5 mg BID
All Cause Death
0 24
Cardiovascular Death
Months
CV Death / MI / Stroke
Estim
ated
Cum
ulati
ve in
cide
nce
(%)
HR 0.84
mITTp=0.020
ITTp=0.007
HR 0.66
mITTp=0.002
ITTp=0.005
10.7%
9.1%
0 24
Placebo
Months Months
4.5%
2.9%
4.1%
2.7%
Rivaroxaban2.5 mg BID
Rivaroxaban2.5 mg BID
Placebo HR 0.68
mITTp=0.002
ITTp=0.004
NNT = 63
Placebo
NNT = 71NNT = 6312 12 12
12%5% 5%
Mega et al, N Engl J Med. 2011 Nov 13
ATLAS ACS 2: Efficacy EndpointsVery Low Dose 2.5 mg BID
Placebo
0 24
Rivaroxaban2.5 mg BID
All Cause Death
0 24
Cardiovascular Death
Months
CV Death / MI / Stroke
Estim
ated
Cum
ulati
ve in
cide
nce
(%)
0 24Months Months
HR 0.85
mITT p=0.039
ITTp=0.011
HR 0.62
mITTp<0.001
ITTp<0.001
2.7%
4.5%
4.2%
2.5%
10.4%
9.0%
Rivaroxaban2.5 mg BID
Rivaroxaban2.5 mg BID
PlaceboPlacebo HR 0.64
mITTp<0.001
ITTp<0.001
NNT = 56NNT = 71 NNT = 5912 12 12
12%5% 5%
Mega et al, N Engl J Med. 2011 Nov 13
ATLAS ACS 2 Efficacy EndpointsVery Low Dose 2.5 mg BIDPatients Treated with ASA + Thienopyridine
0,2 0,20,10,1
0,4
0,1
0,4
0,7
0,2
0
0,2
0,4
0,6
0,8
1
1,2
Fatal ICH Fatal ICH
Placebo
2.5 mg Rivaroxaban
5.0 mg Rivaroxaban
n=4 n=5 n=8n=9 n=6 n=15
p=NS for all comparisons
n=5 n=18n=14
p=NS for Riva vs Placebo
p=NS for Riva 5 vs Placebo
p=NS for Riva 2.5 vs Placebo
p=0.044 for Riva 2.5 vs 5
p=0.009 for Riva vs Placebo
p= 0.005 Riva 5 vs Placebo
P=0.037 for Riva 2.5 vs Placebo
p=0.44 for Riva 2.5 vs 5
Perc
ent (
%)
Mega et al, N Engl J Med. 2011 Nov 13
ATLAS ACS 2: Treatment- Emergent Fatal Bleeds and ICH
ATLAS ACS 2: Conclusion
• Very low dose anticoagulation with rivaroxaban (2.5 mg BID), in addition to antiplatelet therapies, represents an effective strategy to reduce cardiovascular events in patients with a recent ACS.
Mega et al, N Engl J Med. 2011 Nov 13