Activated
Platelet
Clopidogrel
Prasugrel
To neighboring
platelet
IV Gp IIb/IIIa
Inhibitors
Gp IIb/IIIa
fibrinogen
receptor
Aspirin
Activation

Degranulation
COX
Thrombin
Serotonin
Epinephrine
Collagen

Platelet agonists
ADP
ATP
serotonin
calcium
magnesium
TXA, thromboxane; PDGF, platelet-derived growth factor.
Healthy Volunteer
Crossover Study
100
Interpatient
Variability
N=66
60
40
20
0
Interpatient
Variability
IPA at 24 hours (%)
80
Clopidogrel Responder
Clopidogrel Non-responder
-20
Response to
Clopidogrel 300 mg
From Brandt JT AHJ 153: 66e9-66e16,2007
Response to
Prasugrel 60 mg
TRITON: Primary Endpoint
CV Death,MI,Stroke
Primary Endpoint (%)
15
Clopidogrel
12.1
(781)
9.9
(643)
10
Prasugrel
HR 0.81
(0.73-0.90)
P=0.0004
NNT= 46
HR 0.80
P=0.0003
5
HR 0.77
P=0.0001
ITT= 13,608
0
0 30 60 90
180
270
Days
LTFU = 14 (0.1%)
360
450
TRITON TIMI 8 Bilancio efficacia/sicurezza in pz
<75 Yrs, ≥60 kg, e senza pregresso TIA/Stroke
16
Endpoint (%)
14
12
Hazard Ratio, 0.75
(95% CI, 0.66-0.84)
P<0.001
10
CV Death / NF MI / NF Stroke
NNT
Clopidogrel11%
37
8
Prasugrel8.4%
6
Hazard Ratio, 1.240
(95% CI, 0.91-1.69)
P=0.17
4
2
0
0
30
90
Non-CABG TIMI Major Bleeding
NNH
Prasugrel1.95%
222
Clopidogrel1.50%
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
Montalescot C et al . Lancet 2009
TRITON: sottogruppo dei pazienti con STEMI
Endpoint di efficacia
Endpoint di sicurezza
Wiviott SD et al . N Engl J Med 2007
Wiviott SD, N Engl J Med 2007;357(20):2001-15
Distribution of Subjects in
the TRITON – TIMI 38 Trial
Randomized
Subjects
(13608)
Any PCI
(13413)
No PCI (195)
Any Stent(12844)
No Stent
(569)
P=6422, C=6422
BMS Only (6461)
DES Only (5743)
P=3237, C=3224
P=2865, C=2878
PES Only (2766)
SES Only (2454)
P=1404, C=1362
P=1210, C=1244
Mixed
BMS/DES
(640)
Other or
Mixed DES
(523)
BMS = bare metal stent; C = clopidogrel; DES = drug-eluting stent; PES = paclitaxel eluting stent;
PCI = percutaneous coronary intervention; P = prasugrel; SES = Sirolimus eluting stent
Wiviott SD et al. Lancet
2008;371(9621):1353-1363
Clinical Events by Stent Type
(Any Stent)
Pras (%) Clop (%)
Primary Endpoint (CV death/non-fatal MI/non-fatal stroke
CV death/non-fatal MI/UTVR
CV death/non-fatal MI
CV death
MI
UTVR
Revascularization
TIMI major bleeding
Death/non-fatal MI/non-fatal stroke/non-fatal TIMI major bleed
0.5
0.6
0.7
0.8 0.9
Wiviott SD et al. Lancet
2008;371(9621):1353-1363
12
12
9
11
2
2
7
10
2
4
4
2
12
6
2
14
2.0
Hazard Ratio
Prasugrel better
10
10
Clopidogrel better
ARC Definite or Probable Stent
Thrombosis (day 0 to day 450)
2.5
Clopidogrel
% of Subjects
HR 0.48 (0.36-0.64); P<0.0001
2.35
2.0
1.5
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
ARC = Academic Research Consortium
Wiviott SD et al. Lancet 2008;371(9621):13531363
ARC Definite or Probable Early Stent Thrombosis
(0–30 days) in Patients Receiving DES
2.5
% of Subjects
HR 0.29 (0.15-0.56); P=0.0001
2.0
Clopidogrel
1.5
1.44
1.0
Prasugrel
0.5
0.42
0.0
0
5
10
15
20
25
30
Days
ARC = Academic Research Consortium; DES = drug-eluting stent
Wiviott SD et al. Lancet
2008;371(9621):1353-1363
ARC Definite or Probable Late Stent
Thrombosis* in Patients Receiving DES
% of Subjects
2.5
2.0
HR 0.46 (0.22-0.97); P=0.04
1.5
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
ARC = Academic Research Consortium; DES = drug-eluting stent
Wiviott SD et al. Lancet 2008;371(9621):1353-1363