ISO 9001

Leonardo BologneseCardiovascular Department, Arezzo, Italy

Quale terapia antiaggregante nello STEMI?

Prasugrel vs ticagrelor

ISO 9001

Platelet Reactivity in Patients with STEMI Undergoing Primary PCI

Campo G et al. J Am Coll Cardiol 2006;48:2178–85

ISO 9001

Platelet Reactivity in Patients with STEMI Undergoing Primary PCI

Campo G et al. J Am Coll Cardiol 2006;48:2178–85

ISO 9001

�The optimum loading dose of clopidogrel has not been established

�The high pretreatment platelet reactivity in STEMI patients seems to seriously affect the rapidity of the time-dependent inhibition of platelets after clopidogrel loading; high variability of response

�No data are available on clopidogrel in the setting of primary PCI

Clopidogrel in STEMI

ISO 9001

Prasugrel in TRITON-STEMI

TIMI major bleedingTIMI major bleedingPrimary ischaemic EPPrimary ischaemic EP

Montalescot G, et al. Lancet 2009;373:723–31

0.5

1.0

2.0

2.5

1.5

2.1

2.4

Time (Days)

p=0.65

0

ClopidogrelPrasugrel

Time (Days)

5

10

15

0

0 50 100 150 200 250 300 350 400 450

Pro

po

rtio

n o

f p

atie

nts

(%

)

9.5

12.4

10.0

HR=0.79 (0.65–0.97) NNT=41

p=0.02RRR=21%

p=0.002

RRR=32%

6.5

150 200 250 300 350 400 450

HR=1.11 (0.70–1.77) NNH=333

0

2

4

All Death

p= 0.04

TRITONTRITON--TIMI 38: TIMI 38: STEMI Cohort Primary Efficacy Endpoint STEMI Cohort Primary Efficacy Endpoint at 15 Months (CV Death, NF MI, NF Stroke)at 15 Months (CV Death, NF MI, NF Stroke)

Montalescot G et al. Lancet 2009;373(9665):723-731

11,6

14,1

12,4

10.0 10,29,6

0

5

10

15

All STEMI Primary PCI Secondary PCI

Pat

ients

(%

)

ClopidogrelPrasugrel

**

*p < 0.05

CV = cardiovascular; NF = non-fatal; MI = myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction

the test for heterogeneity showed the effect was not significant

228 min(138-396)

252 min(162-420)

Montalescot G et al. Lancet 2009;373(9665):723-731

TRITON-TIMI 38: Caratteristiche basali dei pazienti STEMI sottoposti a PCI primaria

ISO 9001ISO 9001 Steg PG, et al. Circulation 2010;122:2131-41

PLATO STEMI

P=0.07

P=0.07

P=0.03 P=0.02

ISO 9001

PLATO STEMI

PLATO MAJOR BLEEDING

N=7544 P=0.76

Steg PG, et al. Circulation 2010;122:2131-41

ICH 0.4% T vs 0.2% C HR=1.46; 95% CI 0.62-3.41; p=0.38

ISO 9001

NEW ESC STEMI GUIDELINES 2012

European Heart Journal 2012 doi:10.1093/eurheartj/ehs215

ISO 9001

The Challenge in Applying Evidence Based Medicine to Clinical Practice!

We do trials in populations

We treat individual patients

Guidelines

ISO 9001

KM curves for the adjudicated primary composite endpoint of CV death, nonfatal MI, or nonfatal stroke over time in the

STEMI populations in PLATO and TRITON trials

PLATO TRITON

Steg PG et al - Circulation. 2010;122:2131-2141 FDA C ardio-Renal Advisory Committee MeetingJuly 28, 2010

ISO 9001

FDA Complete Response Review

KM curves for the adjudicated primary endpoint days 1-30 in the PLATO STEMI population

http://www.accessdata.fda.gov/drugsatfda_docs/nda/2 011/022433Orig1s000TOC.cfm.

ISO 9001

FDA CV Death (Not Including Bleeds)

PLATO TRITON

ISO 9001

FDA MACE after PCI Day 1 But No Later PCI

ISO 9001

Deaths by PCI within or more than 10h

ISO 9001

Patients with PCI <24hrs and NO Open Label Clopidogrel on or Before Randomization Date

http://www.accessdata.fda.gov/drugsatfda_docs/nda/2 011/022433Orig1s000TOC.cfm.

ISO 9001

http://www.accessdata.fda.gov/drugsatfda_docs/nda/2 011/022433Orig1s000TOC.cfm.

Ticagrelor-early PCI adverse interaction in PLATOFDA Complete Response Review

ISO 9001

Between day 0 and day 3: 0.33 vs 0.67%, HR 0.49, p=0.006

Wiviott SD et al. Lancet 2008;371:1353–1363.

Acute Stent Thrombosis with Ticagrelor and Prasugrel

Steg PG et al. Circulation. 2013;128:1055-1065

ISO 9001

Ferreiro JL, Angiolillo DJ. Circ Cardiovasc Interv 2012

NEW APPROACHES: STENT THROMBOSIS

ISO 9001

PLATO STEMI : Insights From the ECG Substudy

Armstrong PW et al. Circulation 2012, 125:514-521

The main effects of ticagrelor may not relate to th e rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by

more powerful platelet inhibition or other mechanis ms

ISO 9001

Angiographic Outcomes in the PLATO Trial

Kunadian V et al. J Am Coll Cardiol Intv 2013;6:671–8 3

ISO 9001

Outcomes in STEMI patients treated with clopidogrel or prasugrel: A propensity adjusted analysis from INFUSE

AMI

SJ Brener TCT 2013

ISO 9001

1-year Outcomes in STEMI pts treated with clopidogrel or prasugrel: A propensity adjusted analysis from INFUSE

AMI

SJ Brener TCT 2013

Adjusted HR P value

ISO 9001

ISO 9001

ISO 9001

�Immediate antiplatelet protection for ticagrelor after coronary intervention seems to be poor

�STEMI patients receiving early PCI have worse outcomes with ticagrelor compared to clopidogrel; the reverse seems to occur with prasugrel

�The main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion (ST resolution, coronary flow and myocardial perfusion )

Some potential implications deriving from post-hoc analyses

ISO 9001

Crtonline.or (accessed October 12, 2013)