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
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
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
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
�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