ACCOAST: what’s new about antiplatelet therapy

1. COI DISCLOSURE FOR DR. MONTALESCOT are available @ http://www.action-coeur.org

2. Clopidogrel Pretreatment

3. CURE Efficacy
CREDO Efficacy
CURE Safety*
CREDO Safety**
Yusuf S, et al. N Engl J Med 2001;345:494-502
Steinhubl SR, et al. JAMA 2002;288:2411-2420

4. CURE: Cardiovascular Death/Myocardial Infarction/Stroke
During First 30 Days
25% NSTEMI (75% UA), ~21% revascularization
Cumulative Hazard Rates
0.06
Placebo + Aspirin
0.05
0.04
Clopidogrel + Aspirin
0.03
RRR=21%
95% CI (0.67-0.92)
p=0.003
0.02
0.01
0.0
0
Number:
Placebo
Clopidogrel
24-48h
6303
6259
10
20
30
Days of Follow-up
6108
6103
5998
6035
5957
5984
CURE Investigators. N Engl J Med 2001;345:494-502

5. CREDO: Effect of the Delay of Pre-treatment– 28 days
P=0.020 for interaction between the delay of pretreatment and the protection against ischemic events
Events (%)
Pre-treatment- No Pren
Clopidogrel treatment
< 6 hrs
7.9
7.0
9.4
851
No-PT
Better
893
6 to 24 hr * 5.8
PT-Clopidogrel
Better
RRR 38.6
P=0.05
RRR 18.5
P=0.23
Overall CREDO Results
0.4
-2
RRR -13.4
P=NS
0.6
0.8
1.0
1.2
Hazard ratio (95% CI)
Placebo
-3
-4
*Significant effect ≥ 15h after loading
-5
Clopidogrel
-6
0
5
10
15
20
25
30
Steinhubl SR, et al JAMA 2002;288:2411-2420
Steinhubl SR, et al. JACC 2006;47:939-943

6. PCI Pre-Treatment
(With 300 mg load)  Events
Trial
CV Death or MI after PCI to 30 days
OR (95% CI)
PCI-CURE
CREDO
PCI-CLARITY
Overall
P=0.004
0.25
0.5
Favors
Pre-treatment
1.0
2.0
Favors
No Pre-treatment
Sabatine. et al. JAMA. 2005;294:1224-1232

7. P2Y12 Pre-treatment Recommendations
Title
Citation
Class
LOE
2011 ESC guidelines for the
management of acute coronary
syndromes in patients
presenting without persistent
ST-segment elevation
European Heart Journal
2011;32:2999–3054
“A P2Y12 inhibitor as
soon as possible”
Clopidogrel 600 mg
Ticagrelor
I
A
I
I
B
B
2010 ESC/EACTS guidelines on
myocardial revascularization
European Heart Journal
2010;31:20:2501–2555
“Clopidogrel 600 mg
as soon as possible”
I
C
2012 ACCF/AHA focused update
of the guideline for the
management of patients with
unstable angina/non-ST-elevation
myocardial infarction
Circulation
2012;126:875–910
“If invasive strategy,
before PCI”
Clopidogrel
Ticagrelor
*Prasugrel
I
I
B
B
2011 ACCF/AHA/SCAI guideline
for percutaneous
coronary intervention
Circulation
2011;124:e574–651
P2Y12 inhibitor
Clopidogrel
Prasugrel
Ticagrelor
I
I
I
I
A
B
B
B
* Prasugrel 60 mg may be considered for administration promptly upon presentation in patients with
UA/NSTEMI for whom PCI is planned, before definition of coronary anatomy if both the risk for bleeding is
low and the need for CABG is considered unlikely (Level of Evidence: IIb – C)

8. PRAGUE-8 - All Patients
PRAGUE-8 - PCI Patients
Widimsky P, et al. Eur Heart J 2008;29:1495-1503
ARMYDA-5 Efficacy
ARMYDA-5 Safety
Di Sciascio G, et al. J Am Coll Cardiol 2010;56:550-557

9. Death
1/204
1/164
13/933
18/1053
32/1313
0/103
1/513
66/4283
0/205
4/171
24/930
24/1063
31/1345
2/96
0/515
85/4325
Relative
Weight [%]
3·03 [0·12-74·80] 1·0%
0·26 [0·03-2·32] 2·2%
0·53 [0·27-1·05] 23·2%
0·75 [0·41-1·40] 28·3%
1·06 [0·64-1·75] 43·1%
0·18 [0·01-3·85] 1·2%
3·02 [0·12-74·25] 1·0%
0·80 [0·57-1·11] 100%
105/3511
114/5087
219/8598
49/1515
14/832
63/2347
0·92 [0·65-1·30]
1·34 [0·77-2·34]
1·04 [0·74-1·46]
68·2%
31·8%
100%
13/923
209/4879
12/217
18/467
6/1481
76/4477
334/12444
19/990
110/1076
6/166
18/574
18/2679
12/332
183/5817
0·73 [0·36-1·49]
0·39 [0·31-0·50]
1·56 [0·57-4·25]
1·24 [0·64-2·41]
0·60 [0·24-1·52]
0·46 [0·25-0·86]
0·68 [0·42-1·09]
16·2%
24·0%
11·9%
17·0%
12·9%
17·8%
100%
Events / Size, Clopidogrel
Pretreatment No Pretreat
Randomized CT
ARMYDA5 Preload
CIPAMI
CLARITY PCI
CREDO
PCI CURE
Davlouros et al.
PRAGUE 8
All N=8,608
OR [CI 95%]
OR=0·80 CI 95% [0·57-1·11] P=0·17
Observational from RCT
ACUITY PCI
REPLACE 2
All
N=10,945
OR=1·04 CI 95% [0·74-1·46] P=0·83
Observational
Amin et al.
Dorler et al.
Fefer et al.
Feldman et al.
Szuk et al.
Chan et al.
All
N=18,261
OR=0·68 CI 95% [0·42-1·09] P=0·11
Pre-treatment better
0
No Pre-treatment better
0.5
1
1.5
2
2.5
3
3.5
4
Bellemain-Appaix A et al. JAMA 2012;308:2507-2516

10. PCI-NSTEACS Death
Major Bleeding
MACE
Randomized CT
CREDO
PCI CURE
All
N=4 774
OR=0.93 CI 95% [0·63-1·36] p=0·69
OR=1·28 CI 95% [0·98-1·67] p=0·07
OR=0·75 CI 95% [0·64-0·87] p=0·0002
OR=1·19 CI 95% [0·90-1·58] p=0·22
OR=1.10 CI 95% [0·94-1·29] p=0·23
Observational from RCT
ACUITY-PCI
All
N=5 026
OR=0·92 CI 95% [0·65-1·30] p=0·65
Observational
Assali
Feldman et al.
TARGET
All
N=6 149
OR=0·58 CI 95% [0·23-1·48] p=0·26
All Studies
N=15 949
0.01
OR=0·81 CI 95% [0·58-1·13]
p=0·22
0.1
PreT better
1
No PreTt better 10 0.1
OR=0·89 CI 95% [0·48-1·65] p=0·72
OR=1·20 CI 95% [1·00-1·44]
p=0·048
PreTt better
1
No PreTt better
OR=0·86 CI 95% [0·59-1·25] p=0·43
OR=0·86 CI 95% [0·70-1·05]
p=0·14
10 0.1
PreTt better
1
No PreTt better
10
Bellemain-Appaix A et al. ESC 2013. P4846

12. ACCOAST design
NSTEMI + Troponin ≥ 1.5 times ULN local lab value
Clopidogrel naive or on long term clopidogrel 75 mg
Randomize 1:1
n~4100 (event driven)
Double-blind
Prasugrel 30 mg
Coronary
Angiography
Coronary
Angiography
Prasugrel 30 mg
Prasugrel 60 mg
PCI
CABG
or
Medical
Management
(no more prasugrel)
Placebo
PCI
CABG
or
Medical
Management
(no prasugrel)
Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days
1° Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa inh. Bailout, at 7 days
Montalescot G et al. Am Heart J 2011;161:650-656

13. Enrollment:
>4,000 patients in 19 Countries
Poland: 847
Sweden: 4
Canada: 146
Netherlands: 142
Belgium: 81
Portugal: 17
Germany: 529
France: 586
Czech Rep: 292
Austria: 172
Italy: 628
Finland: 42
Latvia: 5
Lithuania: 73
Slovakia: 47
Hungary: 134
Romania: 85
Turkey: 112
Israel: 131

14. Baseline Characteristics (I/III)
Characteristics
Age (mean, yrs)
Female sex (%)
Weight (mean, kg)
BMI ≥ 30 (%)
CV risk factors (%)
Diabetes mellitus
Dyslipidemia
Hypertension
Current smoker
Region of enrolment (%)
Eastern Europe/Israel
Western Europe/Canada
Pre-treatment
No Pre-treatment
(N =2037)
64
27
82
29
(N =1996)
64
28.0
82
28
20
45
63
34
20
45
61
33
42
58
42
58

15. Baseline Characteristics (II/III)
Pre-treatment
No Pre-treatment
(N =2037)
(N =1996)
76
24
34
78
22
34
14.6
15.2
4.4
4.2
Femoral
57
57
Radial
43
43
Characteristics
GRACE score (%)
<140
≥140
CRUSADE score (median)
Timing (hr)
Symptom onset to 1st LD, median
 1st LD to coronary angiogram, median
Access (%)‖

16. Baseline Characteristics (III/III)
Concomitant medications through 7 days (%)
Aspirin, (%)
Pre-treatment No Pre-treatment
(N =2037)
(N =1996)
98
98
65
29
0.8
4.7
55
84
90
14
69
30
66
31
0.6
3.3
56
84
90
12
72
27
Antithrombin Use, (%)
UFH
LMWH
Bivalirudin
Fondaparinux
Proton pump inhibitor
Beta blockers
Statins
ARBs
ACE inhibitors
Calcium channel blockers

17. Pharmacodynamic Sub-Study
350
Placebo
LD1
Pre-treatment (30/30)
No Pre-treatment (0/60)
60 mg
LD2
*P<0.05
P2Y12 Reaction Units
300
250
Approximate
time of PCI
200
150
100
30 mg
LD1
*
*
50
0
30 mg
LD2
Pre LD1 Pre LD2
(baseline)
0.5
1
2
3
Hours (post LD2)
Data presented as median ± SEM. * p<0.05 relative to the No pre-treatment group. LD = loading dose.
Pretreatment=Prasugrel 30 mg/Prasugrel 30 mg; No Pre-treatment=Placebo/Prasugrel 60 mg
4
24

18. 1° Efficacy End Point @ 7 + 30 days
(All Patients)
15
CV Death, MI, Stroke,
UR, GPIIb/IIIa Bailout
Pre-treatment
10.8
Endpoint (%)
Pre-treatment
10.0
10
No Pre-treatment
10.8
No Pre-treatment
9.8
5
Hazard Ratio, 1.02
(95% 0.84, 1.25)
P=0.81
Hazard Ratio, 0.997
(95% 0.83, 1.20)
P=0.98
0
0
No. at Risk, Primary
Efficacy End Point:
No pre-treatment
Pre-treatment
5
10
15
20
25
30
1752
1791
1621
1616
Days From First Dose
1996
2037
1788
1821
1775
1809
1769
1802
1762
1797

19. 1° Efficacy Endpoint
(PCI Patients)
CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa inh. bailout
20
CV Death, MI, Stroke,
UR, GPIIb/IIIa Bailout
PCI Cohort
Endpoint (%)
15
Pre-treatment
13.1
No Pre-treatment
13.8
No Pre-treatment
13.1
10
Pre-treatment
14.1
HR, 1.03
(95% 0.84, 1.26)
P=0.77
HR, 1.01
(95% 0.82, 1.24)
P=0.93
5
0
0
No. at Risk, Efficacy
End Point:
No pre-treatment
Pre-treatment
5
10
15
20
25
30
1177
1186
1177
1172
Days From First Dose
1372
1389
1191
1206
1187
1202
1183
1194
1179
1189

20. 1° Efficacy Endpoint Through 7 Days for
Prespecified Subgroups (All Patients)
Total
Patients
Pre-tx
n (%)
No Pre-tx
n (%)
Hazard Ratio
(95% CI)
4033
203 (9.97)
195 (9.77)
1.02 (0.84, 1.25)
PCI
CABG
Medical Management
2781
238
1014
185 (13.21)
9 (7.44)
9 (1.74)
181 (13.11)
8 (6.84)
6 (1.20)
1.01 (0.83, 1.25)
1.08 (0.42, 2.79)
1.45 (0.52, 4.09)
0.54
<75 years
>75 years
3318
715
160 (9.62)
43 (11.53)
162 (9.79)
33 (9.65)
0.99 (0.79, 1.23)
1.20 (0.76, 1.88)
0.45
2923
1110
152 (10.24)
51 (9.24)
149 (10.36)
46 (8.24)
0.99 (0.79, 1.24)
1.14 (0.76, 1.70)
0.54
205
3824
7 (6.80)
195 (10.09)
12 (11.76)
183 (9.68)
0.56 (0.22, 1.43)
1.05 (0.86, 1.28)
0.20
820
3213
46 (11.14)
157 (9.67)
37 (9.09)
158 (9.94)
1.25 (0.81, 1.93)
0.97 (0.78, 1.21)
0.30
232
3801
11 (9.82)
192 (9.97)
13 (10.83)
182 (9.70)
0.91 (0.41, 2.03)
1.03 (0.84, 1.26)
0.76
1990
2008
84 (8.24)
119 (11.91)
105 (10.82)
90 (8.92)
0.76 (0.57, 1.01)
1.36 (1.03, 1.78)
0.004
1998
2003
120 (12.07)
82 (8.02)
109 (10.86)
86 (8.77)
1.13 (0.87, 1.46)
0.91 (0.67, 1.23)
0.30
3079
852
154 (10.05)
44 (9.73)
143 (9.24)
47 (11.75)
1.09 (0.87, 1.37)
0.82 (0.55, 1.24)
0.24
2276
1711
125 (10.96)
76 (8.75)
111 (9.77)
83 (9.86)
1.14 (0.88, 1.47)
0.88 (0.64, 1.20)
0.21
1692
2341
66 (7.65)
137 (11.67)
63 (7.60)
132 (11.31)
Overall (pre-treatment vs. no pre-treatment)
Interaction
P-value†
Age
Sex
Male
Female
Weight
<60 kg
>60 kg
Diabetes
Yes
No
Prior clopidogrel treatment
Yes
No
Time from Sx to LD
<median
>median
Time from first LD to angio/PCI
<median
>median
GRACE score
<140
>140
Access
Femoral
Radial
Region
Eastern Europe/Israel
Western Europe/Canada
0.1
0.2
0.5
Pre-treatment better
1
2
5
No pre-treatment better
*Hazard ratio not evaluated for <10 events.
†Interaction p-value is from a Cox proportional hazards model with treatment, subgroup, and the treatment-by-subgroup
interaction as fixed effects; PCI includes 11 patients with PCI + CABG.
1.02 (0.72, 1.43) 0.93
1.03 (0.81, 1.31)

21. All TIMI (CABG or non-CABG) Major Bleeding
(All Treated patients)
5
Hazard Ratio, 1.90
(95% 1.19, 3.02)
P=0.006
Hazard Ratio, 1.97
(95% 1.26, 3.08)
P=0.002
Endpoint (%)
4
Pre-treatment
2.9
3
Pre-treatment
2.6
2
All TIMI Major Bleeding
1
No Pre-treatment
1.5
0
No Pre-treatment
1.4
0
No. at Risk, All TIMI
Major Bleeding:
No pre-treatment
Pre-treatment
5
10
15
20
25
30
1284
1297
1263
1280
Days From First Dose
1996
2037
1947
1972
1328
1339
1297
1310
1288
1299

22. All TIMI (CABG or Non-CABG) Major Bleeding
(PCI Patients)
5
Endpoint (%)
4
3
HR, 2.69
(95% 1.13, 6.40)
P=0.02
All TIMI Major Bleeding
PCI Cohort
HR, 2.65
(95% 1.23, 5.70)
P=0.010
2
Pre-treatment
1.4
Pre-treatment
1.7
1
No Pre-treatment
0.5
No Pre-treatment
0.7
0
0
No. at Risk, All TIMI
Major Bleeding:
No pre-treatment
Pre-treatment
5
10
15
20
25
30
1268
1280
1249
1269
Days From First Dose
1372
1389
1356
1364
1302
1314
1280
1293
1272
1282

23. All TIMI Major Bleeding for Prespecified
Subgroups Through 7 days (All Treated Patients)
Total
Patients
Pre-tx
(%)
No Pre-tx
(%)
Overall (pre-treatment vs. no pre-treatment)
Hazard Ratio Interaction
(95% CI)
P-value†
52 (2.55)
27 (1.35)
1.90 (1.19, 3.02)
2781
238
1014
22 (1.57) 11 (0.80)
25 (20.66) 16 (13.68)
5 (0.97)
0 (0.00)
1.98 (0.96, 4.09)
1.59 (0.85, 2.98)
NE
0.74
<75 years
>75 years
Age
4033
PCI
CABG
Medical Management*
3318
715
36 (2.16)
16 (4.29)
22 (1.33)
5 (1.46)
1.64 (0.96, 2.78)
2.95 (1.08, 8.05)
0.31
2923
1110
31 (2.09)
21 (3.80)
21 (1.46)
6 (1.08)
1.43 (0.82, 2.49)
3.61 (1.46, 8.95)
0.09
205
3824
5 (4.85)
47 (2.43)
1 (0.98)
26 (1.37)
NE
1.78 (1.10, 2.87)
0.35
820
3213
6 (1.45)
46 (2.83)
6 (1.47)
21 (1.32)
0.98 (0.32, 3.05)
2.16 (1.29, 3.62)
0.22
1990
2008
28 (2.75)
24 (2.40)
18 (1.86)
9 (0.89)
1.50 (0.83, 2.71)
2.70 (1.25, 5.80)
0.23
1998
2003
27 (2.72)
24 (2.35)
12 (1.20)
15 (1.53)
2.28 (1.16, 4.51)
1.54 (0.81, 2.93)
0.41
2051
1789
23 (2.23)
27 (2.97)
10 (0.98) 2.29 (1.09, 4.81)
15 (1.71) 1.75 (0.93, 3.28)
0.59
3079
852
34 (2.22)
16 (3.54)
18 (1.16)
8 (2.00)
1.92 (1.09, 3.41)
1.76 (0.75, 4.12)
0.87
2276
1711
29 (2.54)
22 (2.53)
18 (1.58)
8 (0.95)
1.62 (0.90, 2.91)
2.67 (1.19, 6.00)
0.66
1692
2341
14 (1.62)
38 (3.24)
5 (0.60)
22 (1.89)
2.69 (0.97, 7.47)
1.74 (1.03, 2.94)
0.46
Sex
Male
Female
Weight
<60 kg*
>60 kg
Diabetes
Yes
No
Time from Sx to LD
<median
>median
Time from first LD to angio/PCI
<median
>median
CRUSADE score‡
<median
>median
GRACE score
<140
>140
Access
Femoral
Radial
Region
Eastern Europe/Israel
Western Europe/Canada
0.2
0.5
Pre-treatment better
1
2
5
10
15
No pre-treatment better
*Hazard ratio not evaluated for <10 events.
†Interaction p-value is from a Cox proportional hazards model with treatment, subgroup, and the treatment-by-subgroup interaction as fixed
effects; ‡CRUSADE score is a post-hoc analysis; PCI includes 11 patients with PCI + CABG.

24. % radial access / country
50%
Germany
Austria
Israel
Belgium
Netherlands
Poland
Canada
Romania
Czech Republic
Italy
6
12
32
33
33
33
39
42
45
45
Lithuania
Finland
Hungary
France
79
85
90
92

25. 5 (0.97)
0 (0.00)
1014
2781 22 (1.57) 11 (0.80)
36 (2.16) 22 (1.33)
3318 36 (2.16) 22 (1.33)
3318 25 (20.66) 16 (13.68)
238
16 (4.29) 5 (1.46)
5 (1.46)
715 16 (4.29)
715
5 (0.97)
0 (0.00)
1014
2923 31 (2.09) 21 (1.46)
2923 31 (2.09) 21 (1.46)
3318 36 (2.16) 22 (1.33)
21 (3.80) 6 (1.08)
6 (1.08)
1110 16 (4.29)
1110 21 (3.80)
5 (1.46)
715
NE
1.98 (0.96, 4.09)
1.64 (0.96, 2.78)
1.64 (0.96, 2.78)
1.59 (0.85, 2.98)
2.95 (1.08, 8.05)
2.95 (1.08, 8.05)
NE
1.43 (0.82, 2.49)
1.43 (0.82, 2.49)
1.64 (0.96, 2.78)
3.61 (1.46, 8.95)
3.61 (1.46, 8.95)
2.95 (1.08, 8.05)
Radial vs. Femoral
0.74
0.31
0.31
0.09
0.09
0.31
205
205
2923
3824
3824
1110
5 (4.85)
5 (2.09)
31(4.85)
47(3.80)
47 (2.43)
21 (2.43)
1 (0.98)
1 (1.46)
21(0.98)
26(1.37)
26(1.08)
6 (1.37)
NE
NE
1.43 (0.82, 2.49)
1.78(1.46, 8.95)
(1.10,2.87)
1.78
3.61 (1.10, 2.87)
0.35
0.35
0.09
820
820
205
3213
3213
3824
1990
1990
820
2008
2008
3213
1998
1998
1990
2003
2003
2008
6 (1.45)
6 (1.45)
5 (4.85)
46(2.83)
(2.83)
46 (2.43)
47
28(2.75)
(2.75)
28(1.45)
6 (2.40)
24(2.40)
24 (2.83)
46
27 (2.72)
27 (2.72)
28 (2.75)
24 (2.35)
24 (2.35)
24 (2.40)
6 (1.47)
6 (1.47)
1 (0.98)
21(1.32)
(1.32)
21 (1.37)
26
18 (1.86)
18(1.47)
6 (1.86)
9
9 (0.89)
21(0.89)
(1.32)
12(1.20)
(1.20)
12 (1.86)
18 (1.53)
15
15(0.89)
9 (1.53)
0.98 (0.32, 3.05)
0.98 (0.32, 3.05)
NE
2.16 (1.29, 3.62)
2.16 (1.29, 3.62)
1.78 (1.10, 2.87)
1.50 (0.83, 2.71)
1.50 (0.83, 2.71)
0.98 (0.32, 3.05)
2.70 (1.25, 5.80)
2.70 (1.25, 5.80)
2.16 (1.29, 3.62)
2.28 (1.16, 4.51)
2.28 (1.16, 4.51)
1.50 (0.83, 2.71)
1.54 (0.81, 2.93)
1.54 (0.81, 2.93)
2.70 (1.25, 5.80)
0.22
0.22
0.35
2051
2051
1998
1789
1789
2003
3079
3079
2051
852
852
1789
2276
2276
3079
1711
1711
852
23 (2.23)
23 (2.23)
27 (2.72)
27 (2.97)
27 (2.97)
24 (2.35)
34 (2.22)
34 (2.22)
23 (2.23)
16 (3.54)
16 (3.54)
27 (2.97)
29 (2.54)
29 (2.54)
34 (2.22)
22 (2.53)
22 (2.53)
16 (3.54)
10 (0.98) 2.29 (1.09, 4.81) 0.59
0.59
10 (0.98) 2.29 (1.09, 4.81)
12 (1.20) 2.28 (1.16, 4.51)
0.41
15(1.71) 1.75 (0.93, 3.28)
(1.71) 1.75 (0.93, 3.28)
15 (1.53) 1.54 (0.81, 2.93)
18 (1.16) 1.92 (1.09, 3.41) 0.87
0.87
18 (1.16) 1.92 (1.09, 3.41)
10 (0.98) 2.29 (1.09, 4.81)
0.59
1.76 (0.75, 4.12)
8 (2.00)
8 (1.71) 1.76 (0.75, 4.12)
15(2.00) 1.75 (0.93, 3.28)
18 (1.58) 1.62 (0.90, 2.91) 0.66
0.66
HR
18 (1.58) 1.62 (0.90, 2.91) Int. p
18 (1.16) 1.92 (1.09, 3.41)
2.67 (1.19, 6.00) 0.87
8(0.95)
(0.95) 2.67 (1.19, 6.00)
8 (2.00)
1.76 (0.75, 4.12)
8
1692
2276
1692
1711
2341
2341
14 (1.62)
29 (2.54)
14 (1.62)
22 (2.53)
38 (3.24)
38 (3.24)
5 (0.60)
18(0.60)
5 (1.58)
8 (0.95)
22 (1.89)
22 (1.89)
2.69 (0.97, 7.47)
1.62 (0.90, 2.91)
2.69 (0.97, 7.47)
2.67 (1.19, 6.00)
1.74 (1.03, 2.94)
1.74 (1.03, 2.94)
0.46
0.66
0.46
5 (0.60)
22 (1.89)
2.69 (0.97, 7.47)
1.74 (1.03, 2.94)
0.46
Radial vs. femoral: 61% lower incidence of
TIMI major bleeding not related to CABG
CI
CI
CI
0.23
0.23
0.22
0.41
0.41
0.23
All TIMI Major Bleeding (All treated patients)
FEMORAL
RADIAL
0.2
0.2
0.5
0.5
1
1
2
2
5
5
Pre-treatment better
Pre-treatment better 1
0.2
0.5
No pre-treatment better
2 No pre-treatment better
5
Pre-treatment better
No pre-treatment better
14
10 1692 15 (1.62)
10
15
2341 38 (3.24)
10
15

26. Non-CABG TIMI Major Bleeding Endpoints
Through 7 Days (All Treated Patients)
3,0
Pre-treatment (N=2037)
Most Frequent Locations of Major Bleed
No Pre-treatment (N=1996)
Event Rate (%)
2,5
2,0
P=0.003
1,5
1,33
P=0.002
1,0
0,83
P not evaluable
0,45
0,5
0,05
0
0,15
0,0
N=
27
9
Non-CABG TIMI Major Bleeding
1
0
Fatal Bleeding
17
3
Life Threatening Bleeding

27. Conclusions
● In NSTE-ACS patients managed invasively within 48
hours of admission, pre-treatment with prasugrel does
not reduce major ischemic events through 30 days but
increases major bleeding complications.
● The results are consistent among patients undergoing
PCI supporting treatment with prasugrel once the
coronary anatomy has been defined.
● No subgroup appears to have a favorable risk/benefit
ratio of pre-treatment.
● Reappraisal of routine pre-treatment strategies in NSTEACS is needed.