Randomized Trial to Evaluate the Relative Randomized Trial to Evaluate the Relative PROTECTPROTECTion against Post-PCI Microvascular ion against Post-PCI Microvascular

Dysfunction and Post-PCI Ischemia among Dysfunction and Post-PCI Ischemia among Anti-Platelet and Anti-Thrombotic AgentsAnti-Platelet and Anti-Thrombotic Agents

Randomized Trial to Evaluate the Relative Randomized Trial to Evaluate the Relative PROTECTPROTECTion against Post-PCI Microvascular ion against Post-PCI Microvascular

Dysfunction and Post-PCI Ischemia among Dysfunction and Post-PCI Ischemia among Anti-Platelet and Anti-Thrombotic AgentsAnti-Platelet and Anti-Thrombotic Agents

PROTECT – TIMI 30 TrialPROTECT – TIMI 30 TrialPROTECT – TIMI 30 TrialPROTECT – TIMI 30 Trial

Unresolved Issues Among UA / NSTEMI Patients Unresolved Issues Among UA / NSTEMI Patients Undergoing PCIUndergoing PCI

• What is the magnitude of the incremental benefit provided What is the magnitude of the incremental benefit provided by the addition of an intravenous antiplatelet agent (a GP by the addition of an intravenous antiplatelet agent (a GP IIb-IIIa inhibitor) to antithrombotic agents?IIb-IIIa inhibitor) to antithrombotic agents?

• What is the magnitude and importance of ongoing What is the magnitude and importance of ongoing ischemia, myonecrosis and inflammation following PCI ischemia, myonecrosis and inflammation following PCI and how do antiplatelet and antithrombin agents affect and how do antiplatelet and antithrombin agents affect these processes?these processes?

• How do we balance the risks (bleeding) and benefits How do we balance the risks (bleeding) and benefits (reduced myonecrosis) of these agents?(reduced myonecrosis) of these agents?

PROTECT: Goals (Continued)PROTECT: Goals (Continued)PROTECT: Goals (Continued)PROTECT: Goals (Continued)

• Efficacy:Efficacy:

– Myocardial perfusionMyocardial perfusion

– MyonecrosisMyonecrosis

– Recurrent ischemiaRecurrent ischemia

– InflammationInflammation

– Rebound thrombin productionRebound thrombin production

– Clinical outcomesClinical outcomes

• Safety:Safety:

– BleedingBleeding

• Efficacy:Efficacy:

– Myocardial perfusionMyocardial perfusion

– MyonecrosisMyonecrosis

– Recurrent ischemiaRecurrent ischemia

– InflammationInflammation

– Rebound thrombin productionRebound thrombin production

– Clinical outcomesClinical outcomes

• Safety:Safety:

– BleedingBleeding

TIMI 30: The PROTECT TrialTIMI 30: The PROTECT TrialTIMI 30: The PROTECT TrialTIMI 30: The PROTECT Trial

High-risk UA/NSTEMI for PCI of a native coronary artery with either

DM; or + Troponin; or ST 0.5 mm; or TRS > 3

BivalirudinBivalirudin0.75 mg/kg IVB + 0.75 mg/kg IVB +

1.75 mg/kg/h 1.75 mg/kg/h

EptifibatideEptifibatide180/180 180/180 g/kg + g/kg +

2 2 g/kg/ming/kg/min

Low Dose UFHLow Dose UFH50 U/kg IVB50 U/kg IVB

ACT 200-250ACT 200-250

+

Low Dose Low Dose EnoxaparinEnoxaparin0.5 mg/kg IV0.5 mg/kg IV

+

TRANSFER TO CATH LAB, DIAGNOSTIC ANGIOGRAM

CONFIRM ELIGIBLE FOR PCI OF CULPRIT IN NATIVE ARTERY

N = 857N = 857

Randomization stratified by Clopidogrel pretreatment >6 h and ≤6 h If not pretreated, then 300 mg Clopidogrel immediately prior to stenting. All tx’d with ASA

Primary Efficacy EndpointPrimary Efficacy EndpointPrimary Efficacy EndpointPrimary Efficacy Endpoint

•Primary Efficacy Endpoint:

– Coronary Flow Reserve (CFR)

• The acceleration in blood flow after adenosine

TIMI Frame Count PRE-adenosine

TIMI Frame Count POST-adenosine

• Interpreted by TIMI Angiographic Core Lab

• Blinded to treatment and clinical outcomes

•Primary Efficacy Endpoint:

– Coronary Flow Reserve (CFR)

• The acceleration in blood flow after adenosine

TIMI Frame Count PRE-adenosine

TIMI Frame Count POST-adenosine

• Interpreted by TIMI Angiographic Core Lab

• Blinded to treatment and clinical outcomes

Higher CFR means greater improvement in blood flow after adenosineHigher CFR means greater improvement in blood flow after adenosine

e.g. a CFR of 2 would mean blood flow was twice as fast after adenosinee.g. a CFR of 2 would mean blood flow was twice as fast after adenosine

Other Angiographic Efficacy Endpoint: TIMI Other Angiographic Efficacy Endpoint: TIMI Myocardial Perfusion (TMP) Grades Myocardial Perfusion (TMP) Grades

Other Angiographic Efficacy Endpoint: TIMI Other Angiographic Efficacy Endpoint: TIMI Myocardial Perfusion (TMP) Grades Myocardial Perfusion (TMP) Grades

0

1

2

3

4

5

6

7

8

0

1

2

3

4

5

6

7

8

6.2%6.2%

4.4%4.4%

2.0%2.0%n = 203n = 203 n = 46n = 46 n = 434n = 434

TMP Grade 3 TMP Grade 3

p = 0.05p = 0.05

Mo

r ta l

ity

( %)

Mo

r ta l

ity

( %)

n = 79n = 79

5.1%5.1%

Gibson et al, Circulation 2000Gibson et al, Circulation 2000

Normal ground glassappearance of blushDye mildly persistent

at end of washout

Normal ground glassappearance of blushDye mildly persistent

at end of washout

Dye strongly persistentat end of washout

Gone by next injection

Dye strongly persistentat end of washout

Gone by next injection

Stain presentBlush persists

on next injection

Stain presentBlush persists

on next injection

No or minimal blushNo or minimal blush

TMP Grade 2 TMP Grade 2 TMP Grade 1 TMP Grade 1 TMP Grade 0 TMP Grade 0