1. Welcome
Ask The Experts
March 24-27, 2007
New Orleans, LA

2. AntiPlatelet Therapy in ACS and PCI Stephen D
AntiPlatelet Therapy in ACS and PCI Stephen D. Wiviott, MD Associate Physician, Cardiovascular Division, Brigham and Women's Hospital Investigator, TIMI Study Group Harvard Medical School Boston, MA

3. Antiplatelet Therapy in ACS and PCI: Challenges and Future Directions
Stephen D. Wiviott Cardiovascular Division Brigham and Women’s Hospital Harvard Medical School TIMI Study Group
Thank you very much for the opportunity to present the 30th annual Paul Ware lecture.
Unfortunately Chris Cannon was not able to be here because of an urgent meeting related to another TIMI trial and he asked me to present in his place.

4. Disclosures Speakers Bureau: Pfizer; CME Honoraria: Eli Lilly, Merck, Pfizer, Sankyo; Accumetrics. Consultancies: Amgen, Transform Pharmaceuticals, Forrest Labs, Biogen-Idec, Sanofi-Aventis TIMI Study Group Receives Research Funding From: Eli Lilly, Sankyo, Merck, Schering Plough, Pfizer, Sanofi-Aventis, Astra Zeneca, CV Therapeutics, Corvas, Accumetrics

5. Dual Antiplatelet Rx for PCI
Circ 102: 624,2000
Dual Antiplatelet Rx for PCI
% MACE
1.5
1.2
0.9
ISAR
FANTASTIC
STARS
MATTIS
CLASSICS

6. Primary End Point - MI/Stroke/CV Death
NSTEACS: Clopidogrel (300/75) vs Placebo
Primary End Point - MI/Stroke/CV Death
11.4%
Placebo + ASA*
9.3%
Clopidogrel + ASA*
Clopidogrel provided a 20% relative risk reduction in the composite outcome of MI, stroke or CV death (95% CI , P < 0.001). Overall there were 719 (11.4%) first events in the placebo group and 582 (9.3%) in the clopidogrel group. The hazard rate curves began to separate within the first few hours after therapy initiation and continued to diverge over the remainder of the trial.
20% RRR
P < 0.001
N = 12,562 3 6 9 12
Months of Follow-Up
* In combination with standard therapy
The CURE Trial Investigators. N Engl J Med. 2001;345:

7. Early Effects of Pre-treatment with Clopidogrel – 28 Day Results
Death, MI, UTVR- PP Population 10 9
8.3% 8
18.5%
RRR
P=0.23 7
6.8% 6
Combined Endpoint
Occurrence (%) 5 4
Looking at the per protocol population of those patients who underwent a PCI, pre-treatment with a 300 mg loading dose of clopidogrel, plus ASA (325 mg) and other standard therapy, led to an 18.5% relative reduction in the risk of the combined endpoint of death, MI, and urgent target vessel revascularization at 28 days that did not achieve statistical significance (6.8% clopidogrel pre-treatment vs. 8.3% no clopidogrel pre-treatment, 95% CI, -14.2, -41.8, p=0.23).1
The relative risk reduction for the other PP endpoints (MI, death, TVR or MI, death) also showed similar risk reductions.
The inability to reach a statistically significant RRR for the primary endpoints has been attributed primarily to a much lower than expected overall event rate in the trial (8.3% actual vs. 13.4% planned) due to good standard of care in the overall study population.
Reference:
1Steinhubl S, Berger P, Tift Mann III J, et al. JAMA. 2002;Vol 288,No 19:
2Steinhubl S, Ellis S, Wolski K et al. Circulation. 2001;103:1403. 3
No-PT - Placebo*
PT- Clopidogrel* 2 1 7 14 21 28
Days From Randomization
PT = Pre-treatment
*Plus ASA and other standard therapies
Steinhubl S, Berger P, Tift Mann III J et al.
JAMA. 2002;Vol 288,No 19:

8. CREDO: Clopidogrel Loading Dose Timing and Risk of MACE
Placebo
- 2
P=0.020
for treatment/timing
interaction
- 3
Log Odds of Death, MI or UTVR at 28 Days
- 4
Clopidogrel
- 5
- 6 5 10 15 20 25 30
Hours Prior to PCI of Study Drug Loading Dose
Steinhubl, et al

9. Limitations of Current thienopyridines
Slow onset: requires prolonged pretreatment for PCI efficacy
Bleeding (especially related to CABG)
Modest levels of platelet inhibition
Variability of response

10. The First Clopidogrel Resistance Study (300 mg): A “Fingerprint” of Clopidogrel Response Variability
2 Hours Hours 24
Resistance
Resistance = 63%
Resistance
Resistance = 31% 20
Patients (%)
Patients (%) 12 10
≤ -30
(-20,-10]
(0,10]
(20,30]
(40,50]
>60
≤ -30
(-20,-10]
(0,10]
(20,30]
(40,50]
>60
 Aggregation (%)
(-30,-20]
(-10,0]
(10,20]
(30,40]
(50,60]
(-30,-20]
(-10,0]
(10,20]
(30,40]
(50,60]
 Aggregation (%)
5 Days Days 22
Resistance
Resistance = 31% 28
Resistance = 15%
Patients (%) 11
Patients (%) 14
Resistance
≤ -10
(-10,0]
(0,10]
(10,20]
(20,30]
(30,40]
(40,50]
(50,60]
>60
≤ -30
(-20,-10]
(0,10]
(20,30]
(40,50]
>60
 Aggregation (%)
(-30,-20]
(-10,0]
(10,20]
(30,40]
(50,60]
 Aggregation (%)
Gurbel PA, et al. Circulation. 2003;107:

11. Potential Mechanisms of Response Variability
Extrinsic Mechanisms
Non-compliance
Under-dosing
Drug-drug interactions
Absorption and/or metabolism
Patient Factors (DM, ACS, etc…)
Intrinsic Mechanisms
P2Y12 receptor affinity (ADP or Drug) or number
Variable response to agonist:
Release
GP IIb/IIIa receptor activation
Wiviott and Antman Circ 2004

12. CYP 3A4 Activity* Correlates Inversely with Platelet Aggregation Following Clopidogrel Loading
100 90 80 70 60 50 40 30 20 10
Platelet Aggregation (%)
r=–0.6
P=0.003
14CO2 Exhaled/Hour (%)
*Erythromycin breath test.
Lau WC, et al. Circulation. 2004;109:

13. Clinical Importance of Response Variability ?
Failure of Therapy
Successful Therapy
Lesser Response
Greater Response
Failure of Therapy = Drug Resistance

14. Clopidogrel Resistance and Increased Risk of Ischemic Events N = 60 Prim PCI for STEMI
5 µM ADP induced plt agg
Death/ACS/CVA by 6 m
120
Clop resist 40 40
100 Q1
P=0.007 30 80 Q2
Baseline (%)
Percent 60 20 Q3 40 Q4 10
6.7 20
Quartiles of response 1 2 3 4 5 6 Q1 Q2 Q3 Q4
Days
Matetzky S, et al. Circulation ;109:
Wiviott SD, Antman EM. Circulation :

15. Platelet Reactivity* Correlates with CK-MB Release: CLEAR Platelet Study
100
P<0.001 90 80
P<0.001
P=0.015 70 60
Mean Platelet Reactivity 50 40 30 20 10
CK-MB (NL)
CK-MB (>1-3x ULN)
CK-MB (>3x ULN)
*5 m ADP.
Gurbel PA, et al. Circulation. 2005;111:

16. Platelet Reactivity in Patients with SAT(N=20) versus no SAT (N=50)
The Clopidogrel REsistance and Stent Thrombosis (CREST) Study
Platelet Reactivity in Patients with SAT(N=20) versus no SAT (N=50)
P<0.001 For Each
LTA – 5 M ADP (%)
LTA – 20 M ADP (%)
Gurbel PA, et al. J Am Coll Cardiol (in press).

17. Increase the Dose: (300 mg vs 600 mg)33
300 mg Clopidogrel 30
600 mg Clopidogrel 27 24
Resistance = 28% (300 mg)
Resistance = 8% (600 mg) 21 18
Patients (%) 15 12 9 6 3
≤-30
(-20,-10]
(0,10]
(20,30]
(40,50]
(60,70]
(-30,-20]
(-10,0]
(10,20]
(30,40]
(50,60]
> 70
D Aggregation (5 µM ADP-induced Aggregation) at 24 Hours
Gurbel PA, et al. J Am Coll Cardiol. 2005;45:

18. Metabolite Concentrations Von Beckenrath et al Circ 2005
ISAR - CHOICE
Metabolite Concentrations
Platelet Aggregation
Von Beckenrath et al Circ 2005

19. ARMYDA-2 Trial: Primary endpoint
255 patients with stable CAD or UA/NSTEMI
4-8 hours prior to PCI
13% received IIb/IIa inhibitors and 20% drug-eluting stents
Primary Composite of death, MI, and target vessel revascularization
p = 0.04
Primary Endpoint: Composite of death, MI, or target vessel revascularization (TVR) at 30 days
Circulation 2005

20. CURRENT/OASIS 7
Clopidogrel optimal loading dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS
Patients with UA/NSTEMI planned for early invasive
Strategy; ie, intend for PCI as early as possible within 24 hrs
RANDOMIZE
Clopidogrel High-Dose Group
Clopidogrel 600 mg loading dose day 1 followed by 150 mg from days 2 to 7; 75 mg from days 8 to 30
Clopidogrel Standard-Dose Group
Clopidogrel 300 mg (+ placebo) day 1 followed by 75 mg (+ placebo) from days 2 to 7; 75 mg from days 8 to 30
RANDOMIZE
RANDOMIZE
ASA low-dose group
At least 300 mg day 1;
75–100 mg from days 2 to 30
ASA high-dose group
At least 300 mg day1;
300–325 mg from days 2 to 30
ASA low-dose group
At least 300 mg day 1;
75–100 mg from days 2 to 30
ASA high-dose group
At least 300 mg day 1;
300–325 mg from days 2 to 30
PCI: Percutaneous coronary intervention
UA/NSTEMI: Unstable angina/non-ST-segment elevation myocardial infarction

21. 85% Inactive Metabolites Esterases
Sem Vasc Med 3:113, 2003
Sankyo Ann Report 51:1,1999
Change the Agent? N S O Cl
CH3 C N S O C H 3 F
Pro-drug
Clopidogrel
Prasugrel
Hydrolysis
(Esterases)
85% Inactive Metabolites Esterases N S O Cl
CH3 C N S O F
Oxidation
(Cytochrome P450)
HOOC
* HS N O F
Active Metabolite O N S Cl
CH3 C
Active Metabolite
HOOC
* HS N O Cl
OCH3

22. Brandt, Payne, Wiviott et al AHJ 2007
Inhibition of Platelet Aggregation (IPA) at 24 Hours (Healthy Volunteers)
100.0
80.0
Interpatient Variability
60.0
Inhibition of Platelet Aggregation (%)
40.0
Interpatient Variability
20.0
0.0
Clopidogrel Responder
Clopidogrel Non-responder
-20.0
Response to Clopidogrel
Response to Prasugrel
*Responder =  25% IPA at 4 and 24 h
Brandt, Payne, Wiviott et al AHJ 2007

23. Inhibition of Platelet Aggregation (Stable Atherosclerosis)70
Loading dose (LD)
Maintenance dose (MD) 60 50 40
Mean IPA (%) 30 20
Prasugrel
(40 mg LD/5 mg MD) 10
Prasugrel
(40 mg LD/7.5 mg MD)
Prasugrel
(60 mg LD/10 mg MD)
Prasugrel
(60 mg LD/15 mg MD)
Clopidogrel
(300 mg LD/75 mg MD) - 10
1/0
1/2
1/4
1/6
7/1
7/2
28/0
28/2
28/4
28/6
Day/Hour Post Dosing
Jernberg, T et al EHJ 2006

24. In Vitro Antiplatelet Effects of Active Metabolites in PRP
(A) Rat
(B) Human 70 80
Platelet aggregation (%)
Platelet aggregation (%) 60 60 * 50 40 **
Prasugrel AM
(IC50 = 51 μM) 40
Prasugrel AM
(IC50 = 26 μM) ** 30 ** **
Clopidogrel AM
(IC50 = 41 μM)
Clopidogrel AM
(IC50 = 21 μM) ** 20 ** 20 ** 10 ** ** ** ** ** 1 10
100
1000 1 10
100
1000
Concentration (μM)
Concentration (μM)
Ogawa, et al ESC 2005.
* P < ** P < 0.01 vs. control

25. Plasma Concentration (ng/ml)
Insights into Potency : Active Metabolite Levels in Humans (Crossover Study)
1000
Prasugrel 60 mg
Clopidogrel 300 mg
100
Plasma Concentration (ng/ml) 10 1
0.1 6 12 18 24
Time in Hr
ISTH 2005 Payne et al, P0952

26. Study Drug in lab; Stratify for GP IIb/IIIa Maintenance Rx for 30 days
STUDY DESIGN
Wiviott et al Circ 2005
PCI with stenting (N=900)
Study Drug in lab; Stratify for GP IIb/IIIa
PRASUGREL
LD 40 mg
MD 7.5 mg
N=200
PRASUGREL
LD 60 mg
MD 10 mg
N=200
PRASUGREL
LD 60 mg
MD 15 mg
N=250
CLOPIDOGREL
LD 300 mg
MD 75 mg
N=250
The trial was a phase II, double-blind, double-dummy, dose-ranging study of patients undergoing either elective or urgent PCI with stenting.
All patients received aspirin 325 mg daily. Patients were randomized to one of three combinations of loading and maintenance doses of prasugrel (low, intermediate or high) or to standard dose clopidogrel with a 300 mg oral loading dose followed by 75 mg daily.
Patients received their loading dose after coronary anatomy was known, and therefore pretreatment interval was short. Therapy was maintained for 30 days.
The primary endpoint was significant non-CABG hemorrhage at 30 days.
Secondary endpoints included TIMI major hemorrhage, MACE and the individual component clinical endpoints.
A study size of 900 patients was selected to provide 80% power to exclude a 2 fold increase in significant bleeding in the prasugrel treated patients compared to clopdogrel.
Maintenance Rx for 30 days
1o endpoint: Significant (non-CABG) bleeding through 30 D
2o endpoints: CV MACE through 30 D, Major Bleeding, Component Clinical Endpoints

27. 10 EP: Significant Non-CABG Bleeding 30 D
Wiviott et al Circ 2005
10 EP: Significant Non-CABG Bleeding 30 D
Clop. vs Prasugrel
Dose Ranging
P = 0.77
P= NS
This slide demonstrates the primary endpoint of the trial, significant non-CABG hemorrhage through 30 days.
The format of this slide will be similar to subsequent results slide, with the comparison between clopidogrel in green and the combined groups of patients receiving prasugrel shown in blue on the left. The dose ranging comparison of prasugrel plotted on the right slide of the slide with increasing doses from left to right beginning with a loading and maintenance dose combinations of 40/7.5, 60/10 and
The bottom of each slide shows the number of patients achieving an endpoint over the number at risk for each treatment group.
There was no significant difference between prasugrel and clopidogrel for the primary endpoint of significant bleeding. 1.2% of patients treated with clopidogrel and 1.7% treated with prasugrel met this endpoint meeting the primary objective. For both treatment groups, the rates of bleeding in JUMBO – TIMI 26 were low and below that expected from previous trials of PCI with thienopyridines.
Treatment Group
Prasugrel LD/MD
R/N
3/254
11/650
3/199
4/200
4/251

28. MI at 30 D Treatment Group Prasugrel LD/MD 20/254 37/650 14/199 13/200
Wiviott et al Circ 2005
RR=0.72 [0.4,1.2]
P = 0.23
P= NS
The first of the component endpoints is myocardial infarction at thirty days. There was a lower, but not statistically significant rate of MI seen on the left hand side of the slide with 7.9% of clopidogrel treated patients having MI compared to 5.7% of the prasugrel treated patients.
The right hand portion of the slide shows the dose response relationship with the lower rates in the higher prasugrel arm.
Treatment Group
Prasugrel LD/MD
R/N
20/254
37/650
14/199
13/200
10/251

29. Implications In patients undergoing PCI, prasugrel:
Demonstrated a similar safety profile to standard dose clopidogrel
Resulted in non-significant, but lower rates of ischemic events compared to patients treated with standard doses of clopidogrel
QUESTION: Would prasugrel, with higher and more consistent levels of platelet inhibition, be superior to clopidogrel in reducing ischemic events in a trial powered to detect a clinically significant difference?
In summary,
In this phase II, dose ranging safety study of prasugrel vs clopidogrel in patients undergoing PCI,
We observed a similar safety profile for prasugrel compared to standard dose clopidogrel. Similar and low rates of hemorrhage were seen in both prasugrel and clopidogrel treatment arms. There was no significant difference in the primary endpoint of TIMI Major plus Minor Hemorrhage. Higher rates of minimal hemorrhage were seen in the highest dose prasugrel arm.
Although not designed and powered to detect differences in clinical efficacy endpoints, we observed non-statistically significant, but consistently lower rates of ischemic events among the prasugrel treated patients compared to those treated with standard doses of clopidogrel.
These data, together with preclinical mechanistic data are encouraging and raise the question; “Would prasugrel be superior to clopidogrel in reducing ischemic events in a trial powered to detect a clinically significant difference?”

30. STUDY DESIGN Enrollment Complete January 2007
ACS (STEMI or UA/NSTEMI) & Planned PCI
Enrollment Complete
January 2007
ASA
N= 13,000
Double-blind
CLOPIDOGREL
300 mg LD/ 75 mg MD
PRASUGREL
60 mg LD/ 10 mg MD
To answer this question, we are currently recruiting up to 850 sites for participation in a global phase 3 trial of prasugrel vs. clopidogrel in patients with acute coronary syndromes with planned PCI, called TRITON-TIMI 38.
This trial will enroll 13,000 patients across the ACS spectrum. Patients will be randomized to either prasugrel or standard doses of clopidogrel. Patients will be followed on maintenance therapy for a median of 12 months. The primary endpoint will be the composite of cardiovascular death, MI and stroke. Important secondary endpoints include bleeding, recurrent ischemia and urgent target vessel revascularization.
Thank you for your attention.
Median duration of therapy - 12 months
1o endpoint: CV death, MI, Stroke
2o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch CV death, MI, UTVR
Wiviott et al, AHJ 2006

31. Implications
Establish the safety and efficacy of prasugrel compared to clopidogrel in patients with ACS undergoing PCI in this registry pathway trial
Proof of Concept:
Does an agent that has higher inhibition of platelet aggregation and less “thienopyridine resistance” result in improved clinical outcomes in an adequately powered clinical trial?
Wiviott et al, AHJ 2006

32. Hypotheses
In the follow up phase, beyond completion of TRITON – TIMI 38*:
Patients withdrawn from thienopyridine at study completion will have a higher rate of stent thrombosis than those continuing therapy in the registry follow up period
Patients treated with DES will have higher rates of stent thrombosis than those treated with BMS over the entire treatment period (trial plus registry)
*Analyses adjusted for baseline, procedural features, and propensity for clopidogrel use

33. Summary of Analytical Groups and Trial/ Registry Timing
Trial Duration
Registry Duration
6-15 Months
24 M Following LPV in TRITON – TIMI 38
TRITON – TIMI 38
Clinical Trial
Continue
DES
Open Label
Thienopyridine
Discontinue
Prasugrel vs Clopidogrel
Continue
BMS
Discontinue
Months
Registry + Trial Duration

34. Prasugrel 10 mg MD vs. Clopidogrel 75 mg MD: Higher IPA During Maintenance Dosing
Loading Dose
Maintenance Doses
100 *
p<0.001 vs. Clop 300 mg or 600 mg LD
Pras 60 mg
Pras 10 mg 80 † !
p<0.001 vs. Clop 300
p<0.05 vs. Clop 300 §p<0.05 vs Clop 300/75
Clop 600 mg
Clop 75 mg 60
Clop 300 mg
Clop 75 mg
Inhibition of Platelet Aggregation (%) 40 20
mean ± SEM 20 μM ADP
0.25
0.5 1 2 4 6 24 3 4 5 6 7 8 9
Time
Hours
Days

35. PRINCIPLE – TIMI 44 (PCI Subjects Only) – Phase I
Protocol Design
PHASE I
Planned Elective PCI
Aggregometry*and Biomarkers√
N < 180
CLOPIDOGREL Naive
Planned GP IIb/IIIa Prohibited
ASA
Clopidogrel
600 mg
Prasugrel
60 mg
0.5, hour post-LD
Aggregometry* and Biomarkers√
Diagnostic Catheterization Anatomy Suitable for PCI
Post Cath† aggregometry
†Or 2 h whichever
is sooner
N = 100
PCI
6, h, Aggregometry*,
biomarkers
Primary Endpoint: Mean IPA (6h) in all treated subjects

36. PRINCIPLE – TIMI 44 (PCI Subjects Only) – Phase II
Protocol Design
Confidential
PCI
PHASE II
Clopidogrel 150 mg x14d
Prasugrel
10 mg x 14d
14 d clinical events, biomarkers √, aggregometry*, CROSSOVER
Prasugrel
10 mg x 14 d
Clopidogrel 150 mg x14d
30 d clinical events,biomarkers √, aggregometry*
Primary Endpoint: Mean IPA (14d&30d) in all treated subjects
√ Biomarkers (VASP, CD40L, P-selectin, LPA, Tn, CK-MB, CRP, MPO)
*Aggregometry: Primary (20 uM ADP), secondary (5 uM ADP), Accumetrics

37. Change the Agent? AZD6140 Characteristics
Class: CPTP* (non-thienopyridine)
Reversible platelet P2Y12 receptor antagonist
Orally active
Rapid onset of action (2 h) with or without a loading dose
Acts directly (no metabolic activation required)
Plasma t½ ~12 h (BID Drug)
AZD6140
*cyclo-pentyl-triazolo-pyrimidine

38. Maximal and Final IPA on Day 1 Clopidogrel Naive Patients
Maximal Extent
Final Extent
100
100 75 75
Mean ± SEM
IPA (%) 50 50 25 25
Source: Study Report Tables 2 4 8 12 2 4 8 12
Time, h
Time, h
AZD mg
AZD mg
AZD mg
CLOP 300 mg
P< for all AZD6140 groups vs
clopidogrel at 4 h
P< for all AZD6140 groups vs
clopidogrel at 4 h

42. UA/NSTEMI (mod-high risk) STEMI (if primary PCI)
All Receiving ASA
Clopidogrel Treated or Naïve
n=18,000 pts
Clopidogrel
If pretreated, no additional load;
if naïve, standard 300 mg load,
then 75 mg od maintenance
(additional 300 mg allowed pre-PCI)
AZD6140
180 mg load, then
90 mg bid maintenance
(additional 90 mg pre-PCI)
12 month maximum exposure
(Min=6 mo, max=12 mo, mean=11 mo)
Primary Endpoint: CV Death/MI/Stroke
Secondary EP: CV Death/MI/Stroke/Revascularization with PCI; CV Death/MI/Stroke; Severe Recurrent Ischemia
ClinicalTrials.gov Identifier: NCT

43. Change The Agent and the Route: Cangrelor?
Low volume of distribution, extensively protein bound
Short half-life (3-5 min), full recovery 20 min
Unlike thienopyridines, direct P2Y12 inhibition, independent of CYP 3A4 metabolism
? Competitive inhibition of clopidogrel

44. Inhibition of Aggregation (%) Fold Increase in Bleeding Time
Clopidogrel Response Variability: Change the Dose and the Route of Administration?
100 8
+ Placebo
+ Aspirin/heparin/GTN 7 80 6 60 5
Inhibition of Aggregation (%)
Fold Increase in Bleeding Time 4 40
Aggregation 3
12 subjects
Separation between antiplatelet and bleeding 2 20
Bleeding time 1 50
100
500
1000
2000
min
Cangrelor (ng.kg-1.min-1)
Recovery period
Stepped infusion period
Nassim MA. J Am Coll Cardiol. 1999;33:225A.

45. CHAMPION PCI (Phase III)
UA, MI, or ACS
n=9,000
Double-blind
CLOPIDOGREL
CANGRELOR
Primary Objective: Superiority or noninferiority of cangrelor versus clopidogrel for PCI
To answer this question, we are currently recruiting up to 850 sites for participation in a global phase 3 trial of prasugrel vs. clopidogrel in patients with acute coronary syndromes with planned PCI, called TRITON-TIMI 38.
This trial will enroll 13,000 patients across the ACS spectrum. Patients will be randomized to either prasugrel or standard doses of clopidogrel. Patients will be followed on maintenance therapy for a median of 12 months. The primary endpoint will be the composite of cardiovascular death, MI and stroke. Important secondary endpoints include bleeding, recurrent ischemia and urgent target vessel revascularization.
Thank you for your attention.
1o endpoint: All-cause mortality, MI, and IDR in the 48 hours after randomization
2o endpoints: All-cause mortality and MI at 48 hours
Accessed September25, 2006, at

46. Summary
ADP induced platelet activation plays a central role in ACS and PCI complications
Thienopyridines have become a key component of therapy
Current thienopyridines have important limitations including response variability
Agents in development offer improved pharmacological profiles, and results of ongoing trials will determine clinical efficacy

47. Question
&
Answer

48. Thank You!
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