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Marco Zimarino, MD, PhDInstitute of Cardiology - University G. d’Annunzio, Chieti (Italy)
Pretreatement with oral P2Y12 inhibitors
in NSTEMI and STEMI
- in favour -
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Recommendations on Timing of P2Y12 Inhibitor and GPI Initiation in Guidelines for NSTE-ACS
Capodanno D, Angiolillo DJ. Circ Cardiovasc Interv. 2015
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Recommendations on Timing of P2Y12 Inhibitor and GPI Initiation in Guidelines for STEMI
Capodanno D, Angiolillo DJ. Circ Cardiovasc Interv. 2015
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Coronary
angiography
PCI
First
medical
contact
Upstream P2Y12 loading (pretreatment)
• More time for the drug to achieve full antiplatelet effects
• More ischemic protection while waiting for coronary angiography
• Less acute stent thrombosis
• Less need for bailout glycoprotein IIIb/IIIa inhibitors
Downstream P2Y12 loading (no pretreatment)
• Reduced bleeding
• No loading dose to patients referred for immediate coronary
artery bypass grafting
• No loading dose to patients with no coronary artery disease
• More time for personalized decisions based on angiographic
and procedural considerations
PROs and CONs of antiplatelet pretreatment
Capodanno D, Angiolillo DJ. Expert Rev Card Ther. 2016
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Pretreatment: different scenarios
A drug is given…
• in the ambulance
• at the referral hospital
• in the medical emergency department
• in the cardiac intensive care unit,
• in the cath-lab after coronary angiography before PCI
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Clopidogrel pretreatment and Mortality
Bellemain-Appaix A on behalf of the ACTION study, Lancet 2012; 308: 2507-17
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Clopidogrel pretreatment and Major Bleeding
Bellemain-Appaix A on behalf of the ACTION study, Lancet 2012; 308: 2507-17
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Mortality after the ACCOAST trial …
Bellemain-Appaix A on behalf of the ACTION study, BMJ 2014; 349: g6269
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Major Bleeding after the ACCOAST trial …
Bellemain-Appaix A on behalf of the ACTION study, BMJ 2014; 349: g6269
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Pretreatment with Prasugrel in NSTE-ACS
Montalescot G, et al. N Engl J Med. 2013;369:999-1010
ACCOAST: 4033 patients with NSTE-ACS coronary angiography within 2 - 48 hours
Randomization to pre- or in-lab treatment with prasugrel
Days From First Dose0 5 10 15 20 25 30
End
po
int
(%)
0
5
10
15
CV Death/MI/Stroke/UR/GPI bailout
Pre-treatment10.810.0
Pre-treatment
Hazard Ratio, 0.997 (95% 0.83, 1.20)P=0.98P=0.81
(95% 0.84, 1.25) Hazard Ratio, 1.02
No Pre-treatment10.8
9.8No Pre-treatment
0 5 10 15 20 25 30
All TIMI Major Bleeding
End
po
int
(%)
0
1
2
3
4
5
Pre-treatment2.9
Pre-treatment2.6
No Pre-treatment1.5
No Pre-treatment1.4
Hazard Ratio, 1.97 (95% 1.26, 3.08)P=0.002
Hazard Ratio, 1.90(95% 1.19, 3.02) P=0.006
Days From First Dose
Independent predictors for TIMI major bleeding HR 95% CI
Pre-treatment with Prasugrel 3.02 1.42–6.43
Femoral access for PCI 2.45 1.11–5.38
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Pretreatment with Ticagrelor in STEMI
Montalescot G on behalf of ATLANTIC investigators, NEJM 2014;371:1016-27
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The course of the level of platelet inhibition
Sibbing et al. Eur Heart J 2016; 37: 1284-95
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Time from first medical contact to coronary angiography in studies of ACS
Capodanno D, Angiolillo DJ. Circ Cardiovasc Interv. 2015
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Delay to peak platelet inhibition for P2Y12 inhibitors
Wiviott SD and PRINCIPLE-TIMI 44 investigators
Circulation. 2007; 116: 2923–32
Husted S et al.
Eur Heart J 2006; 27: 1038–1047
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Prasugrel + Tirofiban in PPCI for STEMI
Valgimigli M on behalf of FABULUS PRO; JACC Intv 2012; 5: 268–77
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Crushing pills to increase bioavailabilityof orally administered P2Y12 receptor inhibitors
Rollini F and CRUSH investigators
JACC 2016; 67: 1994–2004
Parodi G and MOJITO investigators
JACC 2015; 65: 211-2
TicagrelorPrasugrel
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As for P2Y12 inhibitors pre-treatment…
• No robust data to support
• Periprocedural bleeding
• CABG
• Incorrect diagnosis
• Delayed onset of antiplateletactivity
Agreed
Use radial access
<5% in most STEMI trials
<2% in ATLANTIC
10% of pts did not receiverevascularization in ATLANTIC
Crush the pills!