Post on 12-Jan-2016
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If I had an acute coronary syndrome, which antiplatelet agent would I
prefer?
Giuseppe Biondi Zoccai, MD, FSICI-GISEDivision of Cardiology
University of Modena and Reggio Emiliagbiondizoccai@gmail.com
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LEARNING GOALS
• SCOPE OF THE PROBLEM
• MENU A LA CARTE OR TABLE D’HOTE?
• MY OWN RECIPE
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LEARNING GOALS
• SCOPE OF THE PROBLEM
• MENU A LA CARTE OR TABLE D’HOTE?
• MY OWN RECIPE
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ACUTE CORONARY SYNDROMES
Antithrombotictherapy &
(selectively)invasive
management
Stable angina
Unstableangina
Reperfusion(thrombolysis and/or PTCA)
Minutes Hours
DaysWeeks
STEMIUA/NSTEMIAtherothrombosisNew terms
Old terms
Plaque rupture
Non-Q MI Q-MI
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SCOPE OF THE PROBLEMThrombotic eventsThrombotic events
Myocardial Myocardial ischemiaischemia
BleedingBleeding
Peri-procedural Peri-procedural complicationscomplications
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SCOPE OF THE PROBLEMThrombotic eventsThrombotic events
Myocardial Myocardial ischemiaischemia
BleedingBleeding
Peri-procedural Peri-procedural complicationscomplications
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SCOPE OF THE PROBLEM
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SCOPE OF THE PROBLEM: AMI
Capewell et al, Heart 2006Capewell et al, Heart 2006
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SCOPE OF THE PROBLEM: UNSTABLE ANGINA
Capewell et al, Heart 2006Capewell et al, Heart 2006
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PATHWAYS TO THROMBOSIS
****
** **Myers, BUMC Proceedings 2005Myers, BUMC Proceedings 2005
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MULTIPLE VULNERABLE CORONARY PLAQUES IN PATIENTS WITH AMI
Asakura et al, J Am Coll Cardiol 2001Asakura et al, J Am Coll Cardiol 2001
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MULTIPLE RUPTURED CORONARY PLAQUES IN PATIENTS WITH ACS
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ENDOTHELIALIZATION OF STENT STRUTS
Guagliumi et al, Ital Heart J 2003
SES BMS
Guagliumi et al, Ital Heart J 2003
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ON TOP OF THIS:VARIABILITY IN RESPONSE TO ANTITHROMBOTIC THERAPY
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VARIABILITY IN RESPONSEChange in ADP-Induced
Platelet Aggregation75 mg chronic dosing
Serebruany et al, J Am Coll Cardiol 2005 Hochholzer et al, Circulation 2005
Time from loading dose to cath (h)
Maximal aggregation 5 µmol/L ADP (%)following 600 mg loading dose
0 2 4 6 8 100
20
40
60
80
100
N=1001
Num
ber
of P
atie
nts N=544
Relative change in aggregation
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GENETIC VARIABILITY IN RISK OF STENT THROMBOSIS
Mega et al, New Engl J Med 2009
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FAILING STENTS: THROMBOSIS VS RESTENOSIS
Schuchman, New Engl J Med 2006
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MECHANISMS OF THROMBOSIS: VIRCHOW'S TRIAD
BLOOD FLOW
VESSEL
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MECHANISMS OF STENT THROMBOSIS
PATIENT FACTORS
LESION FACTORS
PROCEDURAL & MEDICAL
RX FACTORS
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PREDICTING THROMBOSIS ACCORDING TO DIABETES
Machecourt et al, J Am Coll Cardiol 2009
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PREDICTING THROMBOSIS ACCORDING TO STENT LENGTH
Moreno et al, J Am Coll Cardiol 2005
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PREDICTORS OF STENT THROMBOSIS AFTER ACS
Van Werkum et al, J Am Coll Cardiol 2009
OR
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LEARNING GOALS
• SCOPE OF THE PROBLEM
• MENU A LA CARTE OR TABLE D’HOTE?
• MY OWN RECIPE
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ASPIRIN
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0.00
0.05
0.10
0.15
0.20
0.25
0 3 6 9 12
Months
Pro
bab
ility
of
de
ath
or
MI Placebo
ASA 75 mg
Risk ratio after 1 year 0.5295% Cl 0.37–0.72 (P=0.0001)
Wallentin et al, JACC 1991
ASPIRIN IN UNSTABLE ANGINA
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CLOPIDOGREL
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Cu
mu
lati
ve h
azar
d r
ates
fo
r C
V d
eath
/MI
Days of follow-up
a = median time PCI (10 days)b = 30 days after median time of PCI
0.15
0.10
0.05
0.0
1000
40 100 200 300 400
a b
PlaceboClopidogrel
12.6%
8.8%
1.9% ARR31% RRRP=0.002N=2,658
PCI-CURE
Mehta et al, Lancet 2001
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IMPACT OF ANTIPLATELET THERAPY INTENSITY
Mehta et al, Lancet 2010
Clopidogrel 600+150 mg
Clopidogrel 300+75 mg
P
Definite stent thrombosis
0.7% 1.2% 0.002
Myocardial infarction 2.0% 2.6% 0.012
Stroke 0.4% 0.4% 0.59
Cardiovascular death 1.9% 1.9% 0.68
Myocardial infarction or stent thrombosis
3.0% 3.7% 0.008
Cardiovascular death, myocardial infarction, or
stroke3.9% 4.5% 0.036
30-day results of the CURRENT-OASIS 7 Trial
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SUMMARY OF EVIDENCE ON CLOPIDOGREL LOADING
Lotrionte et al, Am J Cardio 2007;100:1199-1206
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ABCIXIMAB
www.metcardio.orgKastrati et al, JAMA 2006
BENEFITS OF ABCIXIMAB IN ACS PATIENTS PRETREATED WITH 600 MG
CLOPIDOGREL
*Death/MI/urgent TVR
*
600 mg clopidogrel500 mg ASA
>2 h before PCI
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PRASUGREL
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THE TRITON-TIMI 38
0
0.5
1
1.5
2
0 50 100 150 200 250 300 350 400 450
% o
f sub
ject
s ha
ving
D
ES
thro
mbo
sis
Hazard ratio 0.36 [0.22-0.58]P<0.0001
2.31%
0.84%
Days
CLOPIDOGREL
PRASUGREL
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THE TRITON-TIMI 38
Wiviott et al, Lancet 2008;371:1353-63
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TICAGRELOR
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THE PLATO TRIAL
Wallentin et al, NEJM 2009
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THE PLATO TRIAL
Wallentin et al, NEJM 2009
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THE PLATO TRIAL
Wallentin et al, NEJM 2009
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WHEN IS MUCH TOO MUCH?
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LEARNING GOALS
• SCOPE OF THE PROBLEM
• MENU A LA CARTE OR TABLE D’HOTE?
• MY OWN RECIPE
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INDIRECT COMPARISON OF PRASUGREL VS. TICAGRELOR
Funnel plots comparing prasugrel vs. ticagrelor for the risk of key clinical events. Odds ratios (OR) <1.0 favor prasugrel, whereas odds ratios>1.0 favor ticagrelor.
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CABG Medical Rx
Out-of-hospital EMSER
Clopidogrel,Prasugrel orTicagrelor
Ticagrelor Clopidogrel orTicagrelor
Clopidogrel orTicagrelor
Intra-hospital transfer
Wait-and-see
thrombotic risk bleeding risk
thrombotic risk bleeding risk
thrombotic risk bleeding risk
thrombotic risk bleeding risk
Wait-and-see Prasugrel orTicagrelor
pPCI with BMS pPCI with DES
Clopidogrel,Prasugrel orTicagrelor
Coronary angiography
Appraisal of thrombotic and bleeding risks – aspirin unless bleeding risk prohibitive
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TAKE HOME MESSAGE
THROMBOSIS
BLEEDING
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Thank you for your attention
For any correspondence: gbiondizoccai@gmail.com
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