TRITON-TIM 38: Study design

1
TRITON-TIM 38 Study design
N 13,608, moderate-to-high-risk ACS, scheduled
for PCI
Prasugrel 60-mg loading dose then 10 mg daily
post-PCI
Clopidogrel 300-mg loading dose then 75 mg
daily post-PCI
14.5 months median duration of therapy
Primary efficacy endpointCV death, MI,
stroke Key safety endpointTIMI major bleeding
Wiviott SD et al. N Engl J Med. 20073572001-5.
2
TRITON-TIMI 38 Treatment effects on primary
efficacy and key safety endpoints

CV death / MI / stroke
Clopidogrel
12.1
HR 0.81 (0.73-0.90)P 0.0004
?138 events
9.9
10
Endpoint ()
Prasugrel
5
TIMI major bleeding
HR 1.32 (1.03-1.68)P 0.03
Prasugrel
2.4
?35 events
1.8
Clopidogrel
0
0
30
60
90
180
270
360
450
Days
Wiviott SD et al. N Engl J Med. 20073572001-5.
3
PRINCIPLE-TIMI 44 Study designloading dose phase
Prasugrel in Comparison to Clopidogrel for
Inhibition of Platelet Activation and
Aggregation-Thrombolysis in Myocardial Infarction
44
N 201 scheduled for cardiac catheterization
with planned PCI for angina, clopidogrel naïve
and no planned GP IIb/IIIa use
Clopidogrel 600 mg
Prasugrel 60 mg
Coronary Angiography
No PCI (n 89)
PCI (n 112)
Primary endpointInhibition of platelet
aggregation at 6 hours
Wiviott SD et al. Circulation. 2007162923-32.
4
PRINCIPLE-TIMI 44 Study designmaintenance dose
phase
Cohort undergoing PCI only
Prasugrel 10 mg x 14 days
Clopidogrel 150 mg x 14 days
Crossover
Prasugrel 10 mg x 14 days
Clopidogrel 150 mg x 14 days
Primary endpointInhibition of platelet
aggregation after 14 days of each drug
Wiviott SD et al. Circulation. 2007162923-32.
5
PRINCIPLE-TIMI 44 Inhibition of platelet
aggregation with loading dose
Prasugrel 60 mg
IPA ( 20 mM ADP)
Clopidogrel 600 mg
Plt0.0001 vs clopidogrel
Hours
Wiviott SD et al. Circulation. 2007162923-32.
6
PRINCIPLE-TIMI 44 Inhibition of platelet
aggregation with maintenance dose
Prasugrel 10 mg
Prasugrel 10 mg
IPA( 20 mM ADP)
Clopidogrel 150 mg
Clopidogrel 150 mg
Difference Between Treatments 14.9 95 CI 10.6
19.3, Plt0.0001
Days
Wiviott SD et al. Circulation. 2007162923-32.
7
TRITON-TIMI 38, PRINCIPLE-TIMI 44 Implications

• TRITON-TIMI 38 supports hypothesis that greater
  inhibition of platelet aggregation reduces
  ischemic events
• PRINCIPLE-TIMI 44 demonstrates that, in patients
  scheduled for PCI, the TRITON-TIMI 38 dose of
  prasugrel (60 mg/10 mg) is more potent than
  high-dose clopidogrel (600 mg/150mg)
• If clinical goal is to achieve greater inhibition
  of platelet aggregation, this may be achieved
  more effectively with prasugrel vs high-dose
  clopidogrel

Wiviott SD et al. N Engl J Med.
20073572001-5.Wiviott SD et al. Circulation.
2007162923-32.