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Rescue PCI
After failed fibrinolysis in patients with large infarcts if IIa A
performed within 12 h
Fundamental Role of Platelets in ACS
Importance of Antiplatelet Therapy
1 Adhesion
Platelets
2
Plaque Activation
rupture
Activated
platelets
3 Aggregation
STEMI-occlusive thrombus TxA2
NSTEMI = partial lumen occlusion ADP Fibrinogen
PLATO
ticagrelor vs clopidogrel (300 mg 59.5%, 600 mg 19.6%)
59.5% NSTEMI/UA
CURRENT OASIS-7
clopidogrel high (600/150/75) vs low dose (300/75 mg) + ASA high 300-325 mg)
vs low dose (75-100 mg)
70.8% NSTEMI/UA
Metabolic Activation Pathway for
Clopidogrel and Prasugrel
CYP3A O
O CYP1A2 O CYP2C9 OCH3
OCH3 OCH3
CYP2C19 CYP2C19
CYP2B6 CYP2B6 HOOC N
N O N
HS Cl
S Cl S Cl
Es R-130964
Clopidogrel te 2-Oxo-clopidogrel
r as
e (active)
s
O OH
N
S Cl
SR26334
(inactive) CYP3A
O CYP2B6
O O
CYP2C9
O
Esterases N CYP2C19
N O HOOC N
H3 C O
S F S F F
HS
Prasugrel R-95913 R-138727
(inactive) (active)
CYP = cytochrome P-450
Rehmel JL, et al. Drug Metab Dispos 2006;34(4):600-607
Inhibition of Platelet
Aggregation
Clopidogrel 300 mg Prasugrel 60 mg
100
20 µM ADP
* * *
* * *
80 *
60
IPA (%)
*
40
20
0
0 1 2 3 4 5 6 12 16 20 24
Time After Administration (h)
5 *p < 0.01; Mean ± SD Brandt JT et al. Am Heart J 2007;153(1):66.e9-16
Relative Risk and of Primary Endpoint Incidence in
Selected Subgroups
Hazard ratio for Prasugrel Prasugrel Clopidogrel% Reduction
N % in Risk (%)
(95% CI)
Overall 13608 9.9 12.1 19
10
* Clopidogrel
9.5 * *
8.8 8.8 Prasugrel
8 *
6.7 7.0
6.5
6.2
Patients (%)
6
4.9
4 * * p< 0.05
* *
2.6 2.4
2 1.9
1.6 1.3 1.2
0
CV Death/ CV Death/ CV Death/ All-cause NF MI UTVR Stent
NF MI/NF Stroke NF MI/UTVR NF MI Death Thrombosis†
†
Clinically adjudicated according to definite or probable Academic Research Consortium definitions
CV = cardiovascular; MI = myocardial infarction; NF = non-fatal; STEMI = ST-segment elevation myocardial
infarction; UTVR = urgent target vessel revascularisation
Montalescot G et al. Lancet 2009;373(9665):723-731
Prasugrel in combination with aspirin is recommended
as an option for preventing atherothrombotic events in
people with acute coronary syndromes having
percutaneous coronary intervention, only when:
• immediate primary percutaneous coronary intervention for
ST-segment-elevation myocardial infarction is necessary or
MODIFIED
Recommendation
Ticagrelor Clopidogrel P
Dyspnea 13.8% 7.8% <0.001
Syncope 1.1% 0.8% 0.08
Ventr. pauses≥3 5.8% 3.6% 0.01
sec (1st week)
serum 11±22% 9±22% <0.001
creatinine 12m
serum uric 15±52% 7±31% <0.001
acid 12m
CURRENT OASIS-7 Study Design
25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2%)
Planned Early (<24 h) Invasive Management with intended PCI
Ischemic ECG ∆ (80.8%) or ↑cardiac biomarker (42%)
Clopidogrel
Standard Double Hazard 95% CI P
N=12579 N=1250 Ratio
8
Clopidogrel Standard
15% RRR
0.04
Clopidogrel Double
Cumulative Hazard
0.03
0.02
HR 0.85
95% CI 0.74-0.99
0.01
P=0.036
0.0
0 3 6 9 12 15 18 21 24 27 30
Days Mehta S, ESC 2009
BRAVE-3 Trial
STEMI 2003 Registry Collaborators
Witkowski A et al: European Heart Journal 2009; 30: 1736–1743
abciximab
Use of Glycoprotein IIb/IIIa Receptor 40
Antagonists in STEMI
OR and 95% CI of
30-day Mortality
Study Name Year Statistics p-value Dead/Total
SM Abciximab
GPI
Antagonists in STEMI
Modified
Recommendation
abciximab
Fast acting P2Y12 receptor blockers for urgent PCI in pts without
previous antiplatelet therapy