This document summarizes a presentation on antiplatelet therapy and the use of new P2Y12 inhibitors. It discusses clinical trial data comparing clopidogrel to prasugrel and ticagrelor in STEMI and discusses guidelines recommending pretreatment. It also reviews real-world data on the use of new P2Y12 inhibitors from US and European registries, finding their use is increasing slowly. Prasugrel appears to be used in lower risk patients based on registry outcomes, while data on ticagrelor use is more limited. Interpretation of clinical results requires caution due to varying use patterns.

1. ‘‘OCHO PREGUNTAS QUE GENERAN
DEBATE EN ANTIAGREGACIÓN’’
Casa del Corazón. Madrid, 11/11/2014
Dr. José Luis Ferreiro
Hospital Universitario de Bellvitge - IDIBELL
Área de Enfermedades del Corazón
Unidad de Cardiología Intervencionista - Laboratorio de Investigación Cardiovascular

2. CONFLICTOS DE INTERÉS
• Honorarios por conferencias:
– Eli Lilly Co; Daiichi Sankyo, Inc.; AstraZeneca; Roche
Diagnostics
• Consultoría:
– AstraZeneca; Eli Lilly Co; Ferrer; The Medicines Company
• Becas de Investigación:
– AstraZeneca

3. ¿Qué ha Cambiado y Por Qué en
las Recomendaciones de las
Nuevas Guías en Referencia a la
Precarga en IAMCEST?

4. ESC Guidelines: STEMI
2012 STEMI Guidelines
2014 Revascularization Guidelines
Steg PG et al. Eur Heart J. 2012;33:2569-619
Windecker S et al. Eur Heart J. 2014;35:2541-619

5. CLOPIDOGREL: PRIMARY PCI
Ferreiro JL et al. Thromb Haemost 2013;110:110-7

6. STEMI: PRASUGREL AND TICAGRELOR
Pretreatment allowed
TRITON PLATO
N=7544
P=0.07
0
Primary Efficacy Endpoint
12
10
8
6
4
2
0
Clopidogrel
Ticagrelor
HR=0.87 (0.75 to 1.01) NNT=71
6 8 10 12
Cumulative incidence (%)
2 4
Primary Efficacy Endpoint
Time (Days)
15
10
5
0
0 50 100 150 200 250 300 350 400 450
Proportion of patients (%)
9.5
12.4
10.0
HR=0.79 (0.65–0.97) NNT=41
p=0.02
RRR=21%
p=0.002
RRR=32%
6.5
N=3534
P=0.02
Clopidogrel
Prasugrel
Time (Months)
10.8
9.4
p=0.07
RRR=13%
No differences in bleeding
Montalescot G et al. Lancet 2009;373:723-731
Steg PG et al. Circulation 2010;122:2131-2141

7. Clopidogrel Pretreatment Meta-Analysis: RCTs
Bellemain-Appaix A et al. JAMA 2012;308:2507-16

8. Clopidogrel Pretreatment Meta-Analysis: RCTs
Bellemain-Appaix A et al. JAMA 2012;308:2507-16

9. Pretreatment in STEMI
2014 Revascularization Guidelines
Bellemain-Appaix A et al. JAMA 2012;308:2507-16
Windecker S et al. Eur Heart J. 2014;35:2541-619

10. ¿Cómo Encajan los Nuevos
Antiagregantes con un Paciente
Pretratado con Clopidogrel?

11. PLATO: STUDY DESIGN
NSTE-ACS (moderate-to-high risk) STEMI (if primary PCI)
Clopidogrel-treated or -naive;
randomised within 24 hours of index event
(N=18,624)
If pre-treated, no additional loading dose;
if naive, standard 300 mg loading dose,
then 75 mg qd maintenance;
(additional 300 mg allowed pre PCI)
180 mg loading dose, then
90 mg bid maintenance;
(additional 90 mg pre-PCI)
6–12-month exposure
Clopidogrel
Ticagrelor
Primary endpoint: CV death + MI + Stroke
Primary safety endpint: Total major bleeding
PCI = percutaneous coronary intervention; ASA = acetylsalicylic acid;
CV = cardiovascular; TIA = transient ischaemic attack
Wallentin L et al. NEJM 2009;361:1045-57.

12. TRITON TIMI-38: STUDY DESIGN
Exclusion criteria: Any
thienopyridine within 5 days
Wiviott SD et al. NEJM 2007;357:2001-15.
before enrollment

13. “SWITCHING”:
FROM CLOPIDOGREL TO PRASUGREL
Similar findings obtained with MPA to 5 μM ADP, VASP PRI, and Verify Now® PRU
Maximum Platelet Aggregation (%)
100
80
60
40
20
0
Placebo LD/Clopidogrel 75 mg MD (n=33)
*
†
*
p<0.0001 vs clopidogrel 75 mg MD
p<0.0001 vs prasugrel 10 mg MD
0 2 12 24 4 6 8 10 12 14
Time, days
* †
Mean±SE
Time, hours
* †
* *
*
Placebo LD/Prasugrel 10 mg MD (n=36)
Prasugrel 60 mg LD/10 mg MD (n=31)
Angiolillo DJ et al. J Am Coll Cardiol 2010; 56:1017-23.

14. PRASUGREL AFTER CLOPIDOGREL LD
TRIPLET
Study
PRU at 6 hrs
400
300
200
100
0
P=0.188
P=0.809
Placebo/
Pras 60 mg
n = 43
Clop 600 mg/
Pras 60 mg
n = 38
Median
Clop 600 mg/
Pras 30 mg
n = 45
VN-P2Y12, PRU
LS mean* (SE)
57.86
(11.86)
35.61
(12.36)
53.92
(11.74)
LS mean
difference (CI)
22.24
(-10.98, 55.47)
3.93
(-28.20, 36.07)
*MMRM specification: response variable = treatment + visit + treatment by visit + country
Clop=Clopidogrel, CI=Confidence Interval, LS=Least square, MMRM=Mixed-Effect Model Repeated Measure, Pras=Prasugrel, PRU=P2Y12 Reaction Units,
PD=Pharmacodynamic, SE=Standard Error, VN=VerifyNow
Diodati JG et al. Circ Cardiovasc Interv. 2013;6:567-74

15. SWITCH OF NEW P2Y12 ANTAGONISTS
GRAPE Registry: 8 PCI hospitals from Greece
Alexopoulos D et al. Am Heart J. 2014;167:68-76.e2
Use of new APT
(only+switch)
Overall (n=1794) 59.3% (489 + 575)
STEMI (n=941) 63.4% (335 + 262)
NSTEMI + UA
54.7% (154 + 313)
(n=853)
Propensity matched pairs (1-month outcome)

16. IS IT COMMON TO SWITCH?
 Multinational, multicentre,
prospective registry enrolling 2053
STEMI patients
 Clop-LD: 1116 //// Pras-LD: 937
 10 european countries
 Inclusion from June 2011 to June
2013
Clemmensen P et al. Eur Heart J Acute Cardiovasc Care. 2014

17. SAFETY OF PRASUGREL SWITCH AND RELOAD
606 consecutive STEMI patients receiving
prasugrel LD:
CP-load: 90
P-load: 516
Loh JP et al. Am J Cardiol. 2013;111:841-5

18. ¿En Qué Pacientes se Está
Tratando con los Nuevos
Antiagregantes?
¿Qué Información Tenemos?

19. USE OF NEW P2Y12 ANTAGONISTS: US DATA
548 US hospitals (Oct 2009 – Sep 2012): 100,228 STEMI and 158,492 NSTEMI
Sherwood MW et al. J Am Heart Association. 2014;3

20. USE OF NEW P2Y12 ANTAGONISTS: US DATA
Sherwood MW et al. J Am Heart Association. 2014;3

21. USE OF NEW P2Y12 ANTAGONISTS: EU DATA
SCAAR Registry (May 2010 to Dec 2011): ACS and non-ACS undergoing PCI
Damman P et al. Am J Cardiol. 2014;113:64-9

22. USE OF NEW P2Y12 ANTAGONISTS: EU DATA
SCAAR Registry (May 2010 to Dec 2011): ACS and non-ACS undergoing PCI
Damman P et al. Am J Cardiol. 2014;113:64-9

23. USE OF NEW P2Y12 ANTAGONISTS: EU DATA
MULTIPRAC (June 2011 to June 2013): 2,053 STEMI (preloaded) in 10 EU countries
Clemmensen P et al. Eur Heart J Acute Cardiovasc Care. 2014

24. USE OF NEW P2Y12 ANTAGONISTS: EU DATA
MULTIPRAC (June 2011 to June 2013): 2,053 STEMI (preloaded) in 10 EU countries
Clemmensen P et al. Eur Heart J Acute Cardiovasc Care. 2014

25. USE OF NEW P2Y12 ANTAGONISTS: EU DATA
MULTIPRAC (June 2011 to June 2013): 2,053 STEMI (preloaded) in 10 EU countries
Clemmensen P et al. Eur Heart J Acute Cardiovasc Care. 2014

26. USE OF NEW P2Y12 ANTAGONISTS
SWEDE-HEART Registry
STEMI NSTEACS
Orange = Clopidogrel and
Ticagrelor
Purple = Ticagrelor
Yellow = Clopidogrel and
Prasugrel
Pink = Prasugrel
Green = Clopidogrel
Wallentin L et al. Thromb Haemost. 2014;112

27. CONCLUSIONES
• Pocos registros a gran escala publicados que permitan
identificar las características de ptes que reciben nuevos
antiagregantes vs. clopidogrel
• El uso de los nuevos antiagregantes va aumentando
lenta pero progresivamente
• Prasugrel: Uso en pacientes de relativo bajo riesgo
– Bajas tasas de eventos isquémicos y de sangrado
– Beneficio clínico en registros (sesgo de selección)
• Ticagrelor: Escasez de datos
– Uso podría ser en espectro más amplio
• Interpretación de resultados clínicos debe ser prudente
(diferentes patrones de uso)

28. GRACIAS POR SU ATENCIÓN