Quale terapia antiaggregante nello STEMI? Prasugrel vs ticagrelor
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1 Quale terapia antiaggregante nello STEMI? Prasugrel vs ticagrelor Leonardo Bolognese Cardiovascular Department, Arezzo, Italy
2 Platelet Reactivity in Patients with STEMI Undergoing Primary PCI Campo G et al. J Am Coll Cardiol 2006;48:
3 Platelet Reactivity in Patients with STEMI Undergoing Primary PCI Campo G et al. J Am Coll Cardiol 2006;48:
4 Clopidogrel in STEMI 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
5 Prasugrel in TRITON-STEMI Primary ischaemic EP TIMI major bleeding Proportion of patients (%) p=0.002 RRR=32% Time (Days) HR=0.79 ( ) NNT= p=0.02 RRR=21% p= 0.04 All Death Clopidogrel Prasugrel HR=1.11 ( ) NNH= p= Time (Days) Montalescot G, et al. Lancet 2009;373:723 31
6 TRITON-TIMI TIMI 38: STEMI Cohort Primary Efficacy Endpoint at 15 Months (CV Death, NF MI, NF Stroke) Patients (%) ,4 * 11, ,2 14,1 the test for heterogeneity showed the effect was not significant * 9,6 Clopidogrel Prasugrel *p < All STEMI Primary PCI Secondary PCI CV = cardiovascular; NF = non-fatal; MI = myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction Montalescot G et al. Lancet 2009;373(9665):
7 TRITON-TIMI 38: Caratteristiche basali dei pazienti STEMI sottoposti a PCI primaria 228 min ( ) 252 min ( ) Montalescot G et al. Lancet 2009;373(9665):
8 PLATO STEMI P=0.07 P=0.07 P=0.03 P=0.02 Steg PG, et al. Circulation 2010;122:
9 PLATO STEMI PLATO MAJOR BLEEDING N=7544 P=0.76 ICH 0.4% T vs 0.2% C HR=1.46; 95% CI ; p=0.38 Steg PG, et al. Circulation 2010;122:
10 NEW ESC STEMI GUIDELINES 2012 European Heart Journal 2012 doi: /eurheartj/ehs215
11 The Challenge in Applying Evidence Based Medicine to Clinical Practice! We do trials in populations Guidelines We treat individual patients
12 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: FDA Cardio-Renal Advisory Committee Meeting July 28, 2010
13 KM curves for the adjudicated primary endpoint days 1-30 in the PLATO STEMI population FDA Complete Response Review
14 FDA CV Death (Not Including Bleeds) PLATO TRITON
15 FDA MACE after PCI Day 1 But No Later PCI
16 Deaths by PCI within or more than 10h
17 Patients with PCI <24hrs and NO Open Label Clopidogrel on or Before Randomization Date
18 Ticagrelor-early PCI adverse interaction in PLATO FDA Complete Response Review
19 Acute Stent Thrombosis with Ticagrelor and Prasugrel Steg PG et al. Circulation. 2013;128: Between day 0 and day 3: 0.33 vs 0.67%, HR 0.49, p=0.006 Wiviott SD et al. Lancet 2008;371:
20 NEW APPROACHES: STENT THROMBOSIS Ferreiro JL, Angiolillo DJ. Circ Cardiovasc Interv 2012
21 PLATO STEMI : Insights From the ECG Substudy The main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by more powerful platelet inhibition or other mechanisms Armstrong PW et al. Circulation 2012, 125:
22 Angiographic Outcomes in the PLATO Trial Kunadian V et al. J Am Coll Cardiol Intv 2013;6:671 83
23 Outcomes in STEMI patients treated with clopidogrel or prasugrel: A propensity adjusted analysis from INFUSE AMI SJ Brener TCT 2013
24 1-year Outcomes in STEMI pts treated with clopidogrel or prasugrel: A propensity adjusted analysis from INFUSE AMI Adjusted HR P value SJ Brener TCT 2013
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27 Some potential implications deriving from post-hoc analyses 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)
28 Crtonline.or (accessed October 12, 2013)
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