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COI DISCLOSURE FOR DR. COLLET are available @ http://www.action-coeur.org
Jean-Philippe COLLET
NSTE-ACS in the Real World of All-comers
No ANGIO-No PCIMed TT
CABG
PCIMandelzweig et al., Eur Heart J. 2006;27:2285-2293O’ Donoghue et al; JAMA 2008; 300: 71–80.Patel et al; Am Heart J 2006; 152: 641–47.
10%
35%
35%
20%
ANGIO-No PCIMed TT
BENEFIT OF PRE-TTT ?
Symptoms Onset
EMS or Non-PCI center
Ris
k
Identification
Thera
peutic
str
ate
gy
Very high Very high
High High
Intermediate Intermediate
Invasive(<72hr)
Earlyinvasive(<24hr)
Immediateinvasive(<2hr)
Low Low
Non-invasive testing if
appropriate
First medical contact -> NSTE-ACS diagnosis
PCI center
Immediate transfer to PCI center
Same day transfer
Transfer
Transfer
Optional
Selection of NSTE-ACS treatment strategy
www.escardio.org/guidelines
Oral Antiplatelet Therapy in NSTE-ACS
Recommendations Antiplatelet therapy Classa Levelb
Oral Antiplatelet Therapy
A P2Y12 inhibitor is recommended, in addition to aspirin, for 12 months unless there are
contra-indications*I A
It is not recommended to administer prasugrel in patients in whom coronary
anatomy is not known.
III B
*Contra-indications for ticagrelor: previous intracranial haemorrhage or ongoing bleeds. Contra-indications for prasugrel:
previous intracranial haemorrhage, previous stroke or transient ischaemic attack, or ongoing bleeds; prasugrel is
generally not recommended for patients aged 75 years or more or with body weight <60 kg.
Recommendations Antiplatelet therapy in patients in need for OAC Classa Levelb
Oral Antiplatelet Therapy
Itnitial DAPT with aspirin plus a P2Y12 inhibitor in addition to OAC before coronary
angiography is not recommended
III C
ESC 2015 NSTE-ACS Guidelines
Pre-treatment in NSTE-ACS + PCI (Rx trials)
Bellemain-Appaix A, BMJ. 2014 Oct 24;349:g626
CURE vs. ACCOAST according to PCI
0
2
4
6
8
10
12
14
16
CURE-PCI ACCOAST-PCI CURE-PCI ACCOAST-PCI
Placebo
Clopidogrel
Prasugrel
Ischem
icendpoin
t(%
)
After PCIUp to 30 days
Before PCI
Mehta SR et al. Lancet 2001;358:527-533 Montalescot G et al. N Engl J Med.2013;369:999-1010
CURE vs. ACCOAST according to PCI
0
0,5
1
1,5
2
2,5
3
3,5
4
4,5
5
CURE-PCI ACCOAST-PCI
placebo
clopidogrel
prasugrel
Ma
jor
ble
ed
ing
(%)
Mehta SR et al. Lancet 2001;358:527-533 Montalescot G et al. N Engl J Med.2013;369:999-1010
Ticagrelor data
●No dedicated study exists assessing early (i.e.
before coronary angiography) vs. delayed (i.e.
after coronary angiography) ticagrelor
●A drug approach instead of a Strategy
The only dedicated study for ticagrelo is
ongoing : Dubius study
www.escardio.org/guidelines
Antiplatelet therapy for STEMI undergoing PCI
Recommendations Classa Levelb
Antiplatelet therapy
P2Y12 inhibitors should be given at time of first medical contact. I B
ESC 2014 MYOCARDIAL REVASC Guidelines
0 0,5 1 1,5 2 2,5 3 3,5 4
Events / Size, Clopidogrel OR [CI 95%] Relative Weight [%]Pretreatment No
4/17124/930
28/1101
0·26 [0·03-2·32]0·53 [0·27-1·05]0·50 [0·26-0·96]
8·7%91·3%100%
110/10766/166
116/1242
0·39 [0·31-0·50]1·56 [0·57-4·25]0·72 [0·19-2·75]
56·4%43·6%100%
1/16413/933
14/1097
209/487912/217
221/5096OR=0·72 CI 95% [0·19-2·75] p=0·63
RCT*
Observational studies
CIPAMICLARITY PCIAll
Dorler et al.Fefer et al.All
15/17110/930
25/1101
0·97 [0·45-2·08]0·50 [0·17-1·46]0·78 [0·42-1·45]
66·7%33·3%100%
15/10761/166
16/1242
0·61 [0·34-1·11]2·31 [0·24-22·44]0·75 [0·30-1·88]
85·3%14·7%100%
14/1645/933
19/1097
42/48793/217
45/5096
OR=0·78 CI 95% [0·42-1·45] p=0·42
OR=0·75 CI 95% [0·30-1·88] p=0·53
CIPAMICLARITY PCIAll
Dorler et al.Fefer et al.All
RCT*
Observational studies
DEATH
MAJOR BLEEDING
RCT*
Observational studies
CIPAMICLARITY PCIAll
Dorler et al.Fefer et al.All
MACE12/17158/930
70/1101
0·42 [0·14-1·21]0·57 [0·37-0·88]0·54 [0·36-0·81]
14·2%85·8%100%
173/107656/166
229/1242
0·57 [0·47-0·69]0·54 [0·34-0·86]0·57 [0·48-0·67]
85·5%14·5%100%
5/16434/933
39/1097
480/487947/217
527/5096
No PreTreatment better
* RCT=Randomized ControlledTrials
PreTreatment better
0%, p=0.53
86%, p=0.008
0%, p=0.32
19%, p=0.53
0%, p=0.003
0%, p<0.00001
I2, p value
OR=0·50 CI 95% [0·26-0·96] p=0·04
OR=0·54 CI 95% [0·36-0·81] p=0·003
OR=0·57 CI 95% [0·48-0·67] p<0·00001CLOPIDOGREL
A. Bellemain-Appaix et al.,JAMA2012;308(23):2507-2517
CLOPIDOGREL – Metanalysis
Méta-analyse pPCI STEMI Vlaar et al. Circulation 2008, 118:1828-1836
Major adverse CV events up to 30 days: Kaplan–Meier curves
7
6
5
4
3
2
1
0
Eve
nt
rate
(K
M %
)
Time (days)0 12 24 28 308 204 16
Ticagrelor pre-hospital 41/906 (4.5%) versus ticagrelor in-hospital 42/952 (4.4%)OR 1.03 (95% CI 0.66, 1.0); p=0.9056
Ticagrelor pre-hospitalTicagrelor in-hospital
Major adverse CV events: death, myocardial infarction, stroke or urgent revascularisation
2014 nejm
2
1
Definite acute stent thrombosis up to 30 days: Kaplan–Meier curves
Ticagrelor pre-hospital 2/906 (0.2%) versusticagrelor in-hospital 11/952 (1.2%) OR 0.19 (95% CI 0.04, 0.86), p=0.0225
0 6 12 18 24 302 8 14 20 264 10 16 22 28
Eve
nt
rate
(K
M %
)
0
Time (days)
Ticagrelor pre-hospitalTicagrelor in-hospital
24 hp=0.0078
30 daysp=0.0225
Biases of interpretation
Most of the benefit derives from secondary PCI
Most of the benefit derives from old clopidogrel data
Bellemain-appaix et al. JACC Int (submitted)
CONCLUSIONS
Outdated, Ineffective, Harmful in NSTE-ACS
No access to a cath lab/need to wait several days for a cath → ApplyCURE/PLATO and be ready for the safety consequences.
Treating after the angiogram → flexibility, avoids over-treatment &
select the right treatment for the right patient.
Recommended in STEMI when there is no doubt
with respect to the diagnosis