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IV Gp IIb/IIIa Inhibitors. Aspirin. TXA 2. ADP. Activated Platelet. Clopidogrel Prasugrel. To neighboring platelet. Gp IIb/IIIa fibrinogen receptor. Thrombin Serotonin Epinephrine Collagen. COX. Activation. . . Degranulation. Platelet agonists ADP ATP serotonin
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IV Gp IIb/IIIa Inhibitors Aspirin TXA2 ADP Activated Platelet Clopidogrel Prasugrel To neighboring platelet Gp IIb/IIIa fibrinogen receptor Thrombin Serotonin Epinephrine Collagen COX Activation Degranulation Platelet agonists ADP ATP serotonin calcium magnesium TXA, thromboxane; PDGF, platelet-derived growth factor.
Healthy VolunteerCrossover Study 100 N=66 80 InterpatientVariability 60 IPA at 24 hours (%) 40 InterpatientVariability 20 Clopidogrel Responder 0 Clopidogrel Non-responder -20 Response to Prasugrel 60 mg Response to Clopidogrel 300 mg From Brandt JT AHJ 153: 66e9-66e16,2007
TRITON: Primary EndpointCV Death,MI,Stroke 15 Clopidogrel 12.1(781) 9.9 (643) 10 Primary Endpoint (%) Prasugrel HR 0.81(0.73-0.90)P=0.0004 HR 0.80P=0.0003 HR 0.77P=0.0001 5 NNT= 46 LTFU = 14 (0.1%) ITT= 13,608 0 0 30 60 90 180 270 360 450 Days
TRITON TIMI 8 Bilancio efficacia/sicurezza in pz<75 Yrs, ≥60 kg, e senza pregresso TIA/Stroke 1 6 CV Death / NF MI / NF Stroke 1 4 NNT37 Clopidogrel 11% 1 2 Hazard Ratio, 0.75 (95% CI, 0.66-0.84) P<0.001 1 0 Endpoint (%) 8 Prasugrel 8.4% 6 Non-CABG TIMI Major Bleeding Hazard Ratio, 1.240 (95% CI, 0.91-1.69) P=0.17 NNH222 4 Prasugrel 1.95% 2 Clopidogrel 1.50% 0 0 30 90 180 270 360 450 Days Adapted from Wiviott SD et al NEJM 357: 2001, 2007 Presented at TCT 2009, San Francisco, CA
Prasugrel: a chi darlo? • Rischio emorragico • Comorbidita’ • STEMI versus NSTEMI • Eventi ricorrenti • Trombosi di stent
TRITON: sottogruppo dei pazienti con STEMI Endpoint di sicurezza Endpoint di efficacia Wiviott SD et al . N Engl J Med 2007
Randomized Subjects (13608) Any PCI No PCI (195) (13413) Any Stent(12844) No Stent (569) P=6422, C=6422 Mixed BMS Only (6461) DES Only (5743) BMS/DES P=3237, C=3224 P=2865, C=2878 (640) Other or PES Only (2766) SES Only (2454) Mixed DES P=1404, C=1362 P=1210, C=1244 (523) Distribution of Subjects in the TRITON – TIMI 38 Trial Wiviott SD et al. Lancet 2008;371(9621):1353-1363 BMS = bare metal stent; C = clopidogrel; DES = drug-eluting stent; PES = paclitaxel eluting stent; PCI = percutaneous coronary intervention; P = prasugrel; SES = Sirolimus eluting stent
Clinical Events by Stent Type(Any Stent) Pras (%) Clop (%) 10 12 Primary Endpoint (CV death/non-fatal MI/non-fatal stroke CV death/non-fatal MI/UTVR 10 12 CV death/non-fatal MI 9 11 CV death 2 2 MI 7 10 UTVR 2 4 Revascularization 4 6 TIMI major bleeding 2 2 Death/non-fatal MI/non-fatal stroke/non-fatal TIMI major bleed 12 14 0.5 0.6 0.7 0.8 0.9 2.0 Hazard Ratio Prasugrel better Clopidogrel better Wiviott SD et al. Lancet 2008;371(9621):1353-1363
ARC Definite or Probable Stent Thrombosis (day 0 to day 450) 2.5 Clopidogrel 2.35 HR 0.48 (0.36-0.64); P<0.0001 2.0 1.5 % of Subjects 1.13 1.0 Prasugrel 0.5 1 year: 1.06 vs. 2.15% HR 0.48 (0.36-0.65); P<0.0001 0.0 0 50 100 150 200 250 300 350 400 450 Days Wiviott SD et al. Lancet 2008;371(9621):1353-1363 ARC = Academic Research Consortium
ARC Definite or Probable Early Stent Thrombosis (0–30 days) in Patients Receiving DES 2.5 HR 0.29 (0.15-0.56); P=0.0001 2.0 Clopidogrel 1.5 % of Subjects 1.44 1.0 Prasugrel 0.5 0.42 0.0 0 5 10 15 20 25 30 Days Wiviott SD et al. Lancet 2008;371(9621):1353-1363 ARC = Academic Research Consortium; DES = drug-eluting stent
ARC Definite or Probable Late Stent Thrombosis* in Patients Receiving DES 2.5 2.0 HR 0.46 (0.22-0.97); P=0.04 1.5 % of Subjects 0.91 1.0 Clopidogrel 0.5 Prasugrel 0.42 0.0 30 90 150 210 270 330 390 450 Days *Using landmark analysis for all patients, with events occurring from 0–30 days censored from the analysis Wiviott SD et al. Lancet 2008;371(9621):1353-1363 ARC = Academic Research Consortium; DES = drug-eluting stent