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TITAN T T ime to ime to I I ntegrilin ntegrilin T T herapy in herapy in A A cute cute myocardial myocardial infarctio infarctio N N (TITAN)-TIMI 34 (TITAN)-TIMI 34

Time to Integrilin Therapy in Acute myocardial infarctioN

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Page 1: Time to Integrilin Therapy in Acute myocardial infarctioN

TITANTITAN

TTime to ime to IIntegrilin ntegrilin TTherapy in herapy in AAcute cute

myocardial infarctiomyocardial infarctioNN (TITAN)-TIMI 34(TITAN)-TIMI 34

TTime to ime to IIntegrilin ntegrilin TTherapy in herapy in AAcute cute

myocardial infarctiomyocardial infarctioNN (TITAN)-TIMI 34(TITAN)-TIMI 34

Page 2: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: GoalTITAN-TIMI 34: Goal

To answer the following question:To answer the following question:

Among patients intended to undergo Among patients intended to undergo primary PCI, does a strategy of early primary PCI, does a strategy of early initiation of eptifibatide in the ER prior initiation of eptifibatide in the ER prior to primary PCI yield superior pre-PCI to primary PCI yield superior pre-PCI angiographic outcomes compared to a angiographic outcomes compared to a strategy of initiating eptifibatide in the strategy of initiating eptifibatide in the cardiac catheterization laboratory after cardiac catheterization laboratory after diagnostic angiography?diagnostic angiography?

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 3: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Trial OrganizationTITAN-TIMI 34: Trial Organization

TIMI Study GroupTIMI Study Group Eugene Braunwald, M.D. (Chairman)Eugene Braunwald, M.D. (Chairman)

Brigham and Women’sBrigham and Women’s C. Michael Gibson, M.S., M.D. (Principal Investigator) C. Michael Gibson, M.S., M.D. (Principal Investigator)

HospitalHospital Carolyn McCabe, B.S. (Director)Carolyn McCabe, B.S. (Director)

Ajay Kirtane, M.D. (Co-Investigator)Ajay Kirtane, M.D. (Co-Investigator)

Christopher P. Cannon, M.D. (Co-Investigator)Christopher P. Cannon, M.D. (Co-Investigator)

Polly Fish, B.S. (Project Manager)Polly Fish, B.S. (Project Manager)

Data Coordinating Center Data Coordinating Center TIMI Data Coordinating CenterTIMI Data Coordinating Center

Sabina A. Murphy, M.P.H. (Director Biostatistics)Sabina A. Murphy, M.P.H. (Director Biostatistics)

Jacqueline L. Buros, B.A. (Director Data Management)Jacqueline L. Buros, B.A. (Director Data Management)

Angiographic Core LabAngiographic Core Lab TIMI Angiographic Core LabTIMI Angiographic Core Lab

Ajay Kirtane, M.D. (Principal Investigator)Ajay Kirtane, M.D. (Principal Investigator)

Lauren N. Ciaglo, B.A.Lauren N. Ciaglo, B.A.

EKG Core LabEKG Core Lab TIMI EKG Core LabTIMI EKG Core Lab

Benjamin Scirica, M.D. (Director)Benjamin Scirica, M.D. (Director)© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 4: Time to Integrilin Therapy in Acute myocardial infarctioN

Primary PCIPrimary PCIPrimary PCIPrimary PCI

STEMI < 6 HRS Undergoing Primary PCI (n=343)STEMI < 6 HRS Undergoing Primary PCI (n=343)

TITAN TIMI 34: Study DesignTITAN TIMI 34: Study Design

RANDOMIZERANDOMIZEOpen LabelOpen Label

RANDOMIZERANDOMIZEOpen LabelOpen Label

ASA 160-325 mg po ASA 160-325 mg po HEPARIN 60 U/kg bolus (Max 4000U) and 7U/kg HEPARIN 60 U/kg bolus (Max 4000U) and 7U/kg

infusion (Max 800 U/hr)infusion (Max 800 U/hr)

““EARLY ER EPTIFIBATIDE”EARLY ER EPTIFIBATIDE” ““CATH LAB EPTIFIBATIDE”CATH LAB EPTIFIBATIDE”

EPTIFIBATIDE 180/2.0/180EPTIFIBATIDE 180/2.0/180

TRANSFER TO CATH LABTRANSFER TO CATH LAB

DIAGNOSTIC ANGIODIAGNOSTIC ANGIO

PRIMARY ENDPOINT: Pre PCI TIMI Frame CountPRIMARY ENDPOINT: Pre PCI TIMI Frame CountPRIMARY ENDPOINT: Pre PCI TIMI Frame CountPRIMARY ENDPOINT: Pre PCI TIMI Frame Count

EPTIFIBATIDE 180/2.0/180EPTIFIBATIDE 180/2.0/180

TRANSFER TO CATH LABTRANSFER TO CATH LAB

DIAGNOSTIC ANGIODIAGNOSTIC ANGIO

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 5: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Enrollment CriteriaTITAN-TIMI 34: Enrollment Criteria

Inclusion Criteria:• > 18 years of age• Clinical diagnosis of AMI ( ischemic pain > 20 min. )• Onset of symptoms < 6 hours• ST elevation > 1 mm in 2 contiguous limb leads or >2 mm in

2 contiguous precordial leads

Major Exclusion Criteria:• Hemorrhagic risk factors• Current episode previously treated by fibrinolytics• Cardiogenic shock or hemodynamically significant

arrhythmias

Inclusion Criteria:• > 18 years of age• Clinical diagnosis of AMI ( ischemic pain > 20 min. )• Onset of symptoms < 6 hours• ST elevation > 1 mm in 2 contiguous limb leads or >2 mm in

2 contiguous precordial leads

Major Exclusion Criteria:• Hemorrhagic risk factors• Current episode previously treated by fibrinolytics• Cardiogenic shock or hemodynamically significant

arrhythmias

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 6: Time to Integrilin Therapy in Acute myocardial infarctioN

LADLAD

Frame 1: Frame 1: Dye Dye Touches Both Touches Both

Borders & Borders & Moves Moves

ForwardForward

Frame 0: Frame 0: Dye Dye Touches One Touches One or No Bordersor No Borders

Last Frame Last Frame DefinitionDefinition

Frame 21: Frame 21: Dye Dye firstfirst

enters enters landmark landmark

First Frame First Frame DefinitionDefinition

RCARCA

LCXLCX

DistalDistalLandmarkLandmark

Normal Flow in the Normal Flow in the Absence of MI :Absence of MI :

21.0 21.0 ++ 3.1 frames 3.1 frames

1st branch off posterolateral1st branch off posterolateral

Last branch offmost distal OMLast branch offmost distal OM

“Whale’s tail” or “pitchfork”or most distalbranch LAD atapex

“Whale’s tail” or “pitchfork”or most distalbranch LAD atapex

Gibson, Circulation 1996; 93: 879-888Gibson, Circulation 1996; 93: 879-888

TITAN: Primary Endpoint Corrected TIMI Frame CountTITAN: Primary Endpoint Corrected TIMI Frame Count

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 7: Time to Integrilin Therapy in Acute myocardial infarctioN

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

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

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

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 8: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Angiographic Perfusion ScoreTITAN-TIMI 34: Angiographic Perfusion ScoreTITAN-TIMI 34: Angiographic Perfusion ScoreTITAN-TIMI 34: Angiographic Perfusion Score

• Integrates epicardial and myocardial perfusionIntegrates epicardial and myocardial perfusion• Integrates flow before and after PCIIntegrates flow before and after PCI• Sum of the following:Sum of the following:

TIMI Flow Grade Before PCI (0-3)TIMI Flow Grade Before PCI (0-3)TIMI Myocardial Perfusion Grade Before PCI (0-3)TIMI Myocardial Perfusion Grade Before PCI (0-3)TIMI Flow Grade After PCI (0-3)TIMI Flow Grade After PCI (0-3)TIMI Myocardial Perfusion Grade After PCI (0-3)TIMI Myocardial Perfusion Grade After PCI (0-3)

• Integrates epicardial and myocardial perfusionIntegrates epicardial and myocardial perfusion• Integrates flow before and after PCIIntegrates flow before and after PCI• Sum of the following:Sum of the following:

TIMI Flow Grade Before PCI (0-3)TIMI Flow Grade Before PCI (0-3)TIMI Myocardial Perfusion Grade Before PCI (0-3)TIMI Myocardial Perfusion Grade Before PCI (0-3)TIMI Flow Grade After PCI (0-3)TIMI Flow Grade After PCI (0-3)TIMI Myocardial Perfusion Grade After PCI (0-3)TIMI Myocardial Perfusion Grade After PCI (0-3)

Total Angiographic Perfusion Score: 0 - 12Total Angiographic Perfusion Score: 0 - 12

Gibson CM. Am Heart J. 2004 Aug;148(2):336-40. Gibson CM. Am Heart J. 2004 Aug;148(2):336-40.

Failed 0-3; Partial 4-9; Failed 0-3; Partial 4-9; Full 10-12Full 10-12Failed 0-3; Partial 4-9; Failed 0-3; Partial 4-9; Full 10-12Full 10-12

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 9: Time to Integrilin Therapy in Acute myocardial infarctioN

Relationship of Angiographic Perfusion Score Relationship of Angiographic Perfusion Score to SPECT Infarct Size & Mortalityto SPECT Infarct Size & Mortality

Relationship of Angiographic Perfusion Score Relationship of Angiographic Perfusion Score to SPECT Infarct Size & Mortalityto SPECT Infarct Size & Mortality

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

0

5

10

15

20

25

30

35

40

Failed Partial Full

0

5

10

15

20

25

30

35

40

Failed Partial Full

% S

PE

CT

In

farc

t S

ize

% S

PE

CT

In

farc

t S

ize

Angiographic Perfusion ScoreAngiographic Perfusion Score

35.5%35.5%

16.2%16.2%

12.5%12.5%

p=0.002p=0.002

0

5

10

Failed Partial Full

0

5

10

Failed Partial Full

11.1%11.1%

1.9%1.9%

0.0%0.0%

p=0.01p=0.01

% D

eath

by

30 d

ays

% D

eath

by

30 d

ays

Gibson CM. Am Heart J. 2004 Aug;148(2):336-40. Gibson CM. Am Heart J. 2004 Aug;148(2):336-40.

Page 10: Time to Integrilin Therapy in Acute myocardial infarctioN

Global Perfusion Score MethodologyGlobal Perfusion Score MethodologyGlobal Perfusion Score MethodologyGlobal Perfusion Score Methodology

Flow Grade: □ 0 □ 1 □ 2 □ 3Flow Grade: □ 0 □ 1 □ 2 □ 3

Blush Grade: □ 0 □ 1 □ 2 □ 3Blush Grade: □ 0 □ 1 □ 2 □ 3

Flow Grade: □ 0 □ 1 □ 2 □ 3Flow Grade: □ 0 □ 1 □ 2 □ 3

Blush Grade: □ 0 □ 1 □ 2 □ 3Blush Grade: □ 0 □ 1 □ 2 □ 3

Flow Grade: □ 0 □ 1 □ 2 □ 3Flow Grade: □ 0 □ 1 □ 2 □ 3

Blush Grade: □ 0 □ 1 □ 2 □ 3Blush Grade: □ 0 □ 1 □ 2 □ 3

Flow Grade: □ 0 □ 1 □ 2 □ 3Flow Grade: □ 0 □ 1 □ 2 □ 3

Blush Grade: □ 0 □ 1 □ 2 □ 3Blush Grade: □ 0 □ 1 □ 2 □ 3

Flow Grade: □ 0 □ 1 □ 2 □ 3Flow Grade: □ 0 □ 1 □ 2 □ 3

Blush Grade: □ 0 □ 1 □ 2 □ 3Blush Grade: □ 0 □ 1 □ 2 □ 3

Total Potential Score: 54 points© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 11: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Top 10 Enrolling SitesTITAN-TIMI 34: Top 10 Enrolling Sites

Site NameSite Name Principal Principal InvestigatorInvestigator

Research Research CoordinatorCoordinator EnrollmentEnrollment

11 Mount Clemens General HospitalMount Clemens General Hospital Samer KazzihaSamer Kazziha Rebecca Rebecca RichmondRichmond 3737

22 Carolina Cardiology Associates, PACarolina Cardiology Associates, PA Steve RohrbeckSteve Rohrbeck Tammy HedrickTammy Hedrick 3232

33 University of North CarolinaUniversity of North Carolina Mauricio CohenMauricio Cohen Kim WoodKim Wood 3131

44 Northridge HospitalNorthridge Hospital Ivan RokosIvan Rokos Kanchana Kanchana KarunaratneKarunaratne 3030

55 Tri-State Medical Group, CardiologyTri-State Medical Group, Cardiology Jeffrey LinsJeffrey Lins Gretchen Gretchen KalenakKalenak 2727

66 Genesis Medical CenterGenesis Medical Center Nicolas ShammasNicolas Shammas Caroline SloaneCaroline Sloane 2020

77St. Joseph's Regional Medical St. Joseph's Regional Medical CenterCenter Mahesh BikkinaMahesh Bikkina Karen TurnbullKaren Turnbull 1616

88 University Of CincinnatiUniversity Of Cincinnati Saeb KhourySaeb Khoury Cindy WernerCindy Werner 1515

99 Brigham and Women's HospitalBrigham and Women's Hospital Daniel SimonDaniel Simon Rachel Rachel MonbouquetteMonbouquette 1414

1010 Genesis Healthcare SystemGenesis Healthcare System Abdulhay AlbiriniAbdulhay Albirini Terri CampbellTerri Campbell 1414

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 12: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Top 11-20 Enrolling SitesTITAN-TIMI 34: Top 11-20 Enrolling Sites

Site NameSite Name Principal Principal InvestigatorInvestigator

Research Research CoordinatorCoordinator EnrollmentEnrollment

1111 Trinity Medical CenterTrinity Medical Center Aswartha PothulaAswartha Pothula Cynthia AntonioCynthia Antonio 1111

1212 Vanderbilt University Medical Vanderbilt University Medical CenterCenter David ZhaoDavid Zhao Dawn MyersDawn Myers 1010

1313 Cardiology Associates of Cardiology Associates of MississippiMississippi Barry BertoletBarry Bertolet Kelly GlennKelly Glenn 1010

1414 MedCentral MansfieldMedCentral Mansfield Greg EatonGreg Eaton Kathy JurdenKathy Jurden 99

1515 University Hospitals of ClevelandUniversity Hospitals of Cleveland Tom LassarTom Lassar Stacey MazzurcoStacey Mazzurco 99

1616 Decatur Memorial HospitalDecatur Memorial Hospital Peter KatsiyiannisPeter Katsiyiannis Rebecka SongerRebecka Songer 77

1717 West Chester CardiologyWest Chester Cardiology Mian JanMian Jan Cindy BrockwayCindy Brockway 77

1818 Seattle Cardiovascular ResearchSeattle Cardiovascular Research Thomas AmidonThomas Amidon Lynn RoyalLynn Royal 66

1919 Veterans Affairs Medical Center Veterans Affairs Medical Center (111C2)(111C2) Saeb KhourySaeb Khoury

Jackie EdwardsJackie Edwards 55

2020 Northeast Cardiology AssociatesNortheast Cardiology Associates Peter Ver LeePeter Ver Lee Cindy WhitedCindy Whited 55

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Page 13: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Baseline CharacteristicsTITAN-TIMI 34: Baseline Characteristics

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

CharacteristicCharacteristicER EptifibatideER Eptifibatide

n=174n=174

Cath Lab Cath Lab EptifibatideEptifibatide

n=142n=142P valueP value

Age (yrsAge (yrs++SD)SD) 59.1 +/- 13.1 yrs59.1 +/- 13.1 yrs 60.1 +/- 12.6 yrs60.1 +/- 12.6 yrs NSNS

MaleMale 74.7%74.7% 73.2%73.2% NSNS

HypertensionHypertension 42.2%42.2% 40.9%40.9% NSNS

HyperlipidemiaHyperlipidemia 32.2%32.2% 31.2%31.2% NSNS

Current smokerCurrent smoker 49.4%49.4% 40.1%40.1% NSNS

DiabetesDiabetes 15.5%15.5% 18.3%18.3% NSNS

Prior MIPrior MI 14.9%14.9% 10.6%10.6% NSNS

Anterior MIAnterior MI 35.2%35.2% 39.6%39.6% NSNS

Page 14: Time to Integrilin Therapy in Acute myocardial infarctioN

0%

20%

40%

0 50 100

% P

atie

nts

wit

h C

TF

C <

X a

xis

0%

20%

40%

0 50 100

% P

atie

nts

wit

h C

TF

C <

X a

xis

TITAN-TIMI 34 Primary Endpoint:Pre-PCI TIMI Frame Count

TITAN-TIMI 34 Primary Endpoint:Pre-PCI TIMI Frame Count

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

p < 0.05p < 0.05

p=0.046 adjusting for infarct locationp=0.046 adjusting for infarct location

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

Frame CountFrame Count

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

0

10

20

30

40

50

60

70

80

90

100

0

10

20

30

40

50

60

70

80

90

100

CT

FC

TF

CC

p < 0.05p < 0.05 84.3 84.3 ++ 30.7 30.7 (n=137)(n=137)

77.5 77.5 ++ 32.2 32.2 (n=168)(n=168)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

Page 15: Time to Integrilin Therapy in Acute myocardial infarctioN

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

0

5

10

15

20

25

30

0

5

10

15

20

25

30

Pre

- P

CI

TM

PG

3 (

%)

Pre

- P

CI

TM

PG

3 (

%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

24.3%24.3%

14.2%14.2%

p = 0.026p = 0.026

(41/169)(41/169) (20/141)(20/141)

p=0.025 adjusting for infarct locationp=0.025 adjusting for infarct location

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

TITAN-TIMI 34: Secondary Angiographic Endpoint TIMI Flow Grades

TITAN-TIMI 34: Secondary Angiographic Endpoint TIMI Flow Grades

0

5

10

15

20

25

30

35

40

45

50

0

5

10

15

20

25

30

35

40

45

50

Pre

- P

CI

TIM

I 2

or

3 F

low

(%

)P

re -

PC

I T

IMI

2 o

r 3

Flo

w (

%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

46.2%46.2%

36.6%36.6%

(79/171)(79/171) (52/142)(52/142)

TIMI 2 or 3TIMI 2 or 3p = 0.087p = 0.087

24%19%p=NSp=NS

TIMI 3TIMI 3

Page 16: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Pre-PCI Flow Throughout HeartTITAN-TIMI 34: Pre-PCI Flow Throughout Heart

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

4238

0

10

20

30

40

50

4238

0

10

20

30

40

50

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

Global Perfusion Global Perfusion ScoreScore

n=125n=125 n=99n=99

p = 0.008p = 0.00855.8

52.1

0

10

20

30

40

50

60

70

55.852.1

0

10

20

30

40

50

60

70

p = 0.03

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

Global Frame Count Global Frame Count (Ave. 3 Arteries)(Ave. 3 Arteries)

Page 17: Time to Integrilin Therapy in Acute myocardial infarctioN

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

Pre

- P

CI

ML

D (

mm

)P

re -

PC

I M

LD

(m

m)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

0.330.33

0.210.21

p = 0.026p = 0.026

(n=169)(n=169) (n=138)(n=138)80

82

84

86

88

90

92

80

82

84

86

88

90

92

Pre

- P

CI

% S

ten

osi

sP

re -

PC

I %

Ste

no

sis

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

87.5%87.5%

91.0%91.0%

p = 0.048p = 0.048

(n=169)(n=169) (n=139)(n=139)

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

TITAN-TIMI 34 Pre-PCI Quantitative AngiographyTITAN-TIMI 34 Pre-PCI Quantitative Angiography

Page 18: Time to Integrilin Therapy in Acute myocardial infarctioN

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

0

5

10

15

20

25

0

5

10

15

20

25

Po

st -

PC

I C

TF

CP

ost

- P

CI

CT

FC

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

20202222

p = 0.14p = 0.14

0

20

40

60

80

100

0

20

40

60

80

100

Po

st -

PC

I T

IMI

3 F

low

(%

)P

ost

- P

CI

TIM

I 3

Flo

w (

%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

86.7%86.7% 89.1%89.1%

p = NSp = NS

0

5

10

15

20

25

30

35

40

0

5

10

15

20

25

30

35

40

Po

st -

PC

I T

MP

G 3

(%

)P

ost

- P

CI

TM

PG

3 (

%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

37.0%37.0% 36.7%36.7%

p = NSp = NS

(47/128)(47/128)(57/154)(57/154)(n=138)(n=138) (n=116)(n=116) (137/158)(137/158) (122/137)(122/137)

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

TITAN-TIMI 34 Post-PCI FlowTITAN-TIMI 34 Post-PCI Flow

Page 19: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Full Angiographic PerfusionTITAN-TIMI 34: Full Angiographic Perfusion

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

0

5

10

15

20

25

0

5

10

15

20

25

Fu

ll A

ng

iog

rap

hic

F

ull

An

gio

gra

ph

ic

Per

fusi

on

(A

PS

10-

12)

%

Per

fusi

on

(A

PS

10-

12)

%

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

21.1%21.1%

12.5%12.5%

p = 0.059p = 0.059

(32/152)(32/152) (16/128)(16/128)

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

Full Angiographic Perfusion previously defined in Gibson CM. Am Heart J. 2004 Aug;148(2):336-40. Full Angiographic Perfusion previously defined in Gibson CM. Am Heart J. 2004 Aug;148(2):336-40.

Page 20: Time to Integrilin Therapy in Acute myocardial infarctioN

TITAN-TIMI 34: Treated as Intended in Protocol Analysis

TITAN-TIMI 34: Treated as Intended in Protocol Analysis

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

ER Group: ER Group: Drug at least 15 minutes before 1Drug at least 15 minutes before 1stst

injection on angioinjection on angio (n=127)(n=127)

Cath Lab Cath Lab Group:Group:

Drug after 1Drug after 1stst injection on injection on angio (n=114)angio (n=114)

First Injection on Angio = Time 0First Injection on Angio = Time 0

0%

25%

50%

75%

100%

-60 -50 -40 -30 -20 -10 0 10 20

% P

atie

nts

wit

h T

ime

fro

m

Bo

lus

to C

ath

<X

axi

s

Page 21: Time to Integrilin Therapy in Acute myocardial infarctioN

0%

20%

40%

0 50 100

% P

ati

en

ts w

ith

CT

FC

<X

ax

is

0%

20%

40%

0 50 100

% P

ati

en

ts w

ith

CT

FC

<X

ax

is

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

p = 0.021p = 0.021

p=0.024 adjusting for infarct locationp=0.024 adjusting for infarct location

Secondary Analysis: Treated per ProtocolSecondary Analysis: Treated per Protocol

TITAN-TIMI 34 Primary Endpoint:Pre-PCI TIMI Frame Count

TITAN-TIMI 34 Primary Endpoint:Pre-PCI TIMI Frame Count

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

Frame CountFrame Count

0

10

20

30

40

50

60

70

80

90

100

0

10

20

30

40

50

60

70

80

90

100

75.3 75.3 ++ 32.1 32.1(n=124)(n=124)

84.4 84.4 ++ 30.7 30.7(n=109)(n=109)

CT

FC

p = 0.021p = 0.021

Cath Lab Cath Lab EptifibatideEptifibatide

EREREptifibatideEptifibatide

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60

80

100

60

80

100

FFAASSTTEERR

FFLLOOWW

TITAN-TIMI 34: Duration of Therapy and Pre-PCI TIMI Frame Count

TITAN-TIMI 34: Duration of Therapy and Pre-PCI TIMI Frame Count

n=165n=165 n=111n=111 n=17n=17

Mea

n T

IMI

Fra

me

Cou

ntM

ean

TIM

I F

ram

e C

ount

Duration of Therapy Before First InjectionDuration of Therapy Before First Injection

p = 0.003 for linear trendp = 0.003 for linear trend

In cath lab to In cath lab to 15 min prior15 min prior

15 min to 6015 min to 60min. priormin. prior

> 60 min. > 60 min. priorprior

85.685.685.685.6

76.676.676.676.6

68.668.668.668.6

Earlier TreatmentEarlier Treatment© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

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TITAN-TIMI 34: Pre-PCI TIMI Grade 2 or 3 Flow and Full PerfusionTITAN-TIMI 34: Pre-PCI TIMI Grade 2 or 3 Flow and Full Perfusion

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

0%

10%

20%

30%

40%

50%

0%

10%

20%

30%

40%

50%

Pre

- P

CI

TIM

I 2

or

3 F

low

(%

)P

re -

PC

I T

IMI

2 o

r 3

Flo

w (

%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

46.8%46.8%

34.2%34.2%

(59/126)(59/126) (39/114)(39/114)

p = 0.047p = 0.047

Secondary Analysis: Treated per ProtocolSecondary Analysis: Treated per Protocol

0%

10%

20%

30%

0%

10%

20%

30%

Fu

ll A

ng

iog

rap

hic

Per

fus

ion

(%

)F

ull

An

gio

gra

ph

ic P

erfu

sio

n (

%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

23.9%23.9%

13.2%13.2%

p = 0.041p = 0.041

Full Angiographic Perfusion previously defined in Gibson CM. Am Heart J. 2004 Aug;148(2):336-40. Full Angiographic Perfusion previously defined in Gibson CM. Am Heart J. 2004 Aug;148(2):336-40.

(28/117)(28/117) (14/106)(14/106)

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© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

2.32.1

0

1

2

3

2.32.1

0

1

2

3

Dea

th (

%)

Dea

th (

%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

DeathDeathp = NSp = NS

2.9

7.1

0

2

4

6

8

2.9

7.1

0

2

4

6

8

CH

F

(%)

CH

F

(%)

EREREptifibatideEptifibatide

Cath Lab Cath Lab EptifibatideEptifibatide

n=173n=173 n=142n=142

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

TITAN-TIMI 34 Clinical Endpoints at Discharge/Day 5

TITAN-TIMI 34 Clinical Endpoints at Discharge/Day 5

CHFCHFp = 0.082p = 0.082

n=173n=173 n=142n=142

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© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

OutcomeOutcomeER ER

Eptifibatide Eptifibatide (n=174)(n=174)

Cath Lab Cath Lab Eptifibatide Eptifibatide

(n=142)(n=142)P-valueP-value

TIMI Major TIMI Major (Hgb (Hgb >5 g/dL or ICH) >5 g/dL or ICH) 1.7%1.7% 3.5%3.5% NSNS

TIMI Minor TIMI Minor (Hgb (Hgb 3-5 g/dL) 3-5 g/dL) 5.2%5.2% 4.2%4.2% NSNS

TIMI Major or MinorTIMI Major or Minor 6.9%6.9% 7.8%7.8% NSNS

Transfusion PRBCTransfusion PRBC 9.8%9.8% 7.0%7.0% NSNS

Stroke or ICHStroke or ICH 0.0%0.0% 0.0%0.0% NSNS

Thrombocytopenia (Plt. < 100K)Thrombocytopenia (Plt. < 100K) 2.3%2.3% 1.4%1.4% NSNS

TITAN-TIMI 34: Bleeding EventsTITAN-TIMI 34: Bleeding EventsTITAN-TIMI 34: Bleeding EventsTITAN-TIMI 34: Bleeding EventsNon CABG Through Discharge; Site AssessmentNon CABG Through Discharge; Site Assessment

Primary Analysis: Modified Intent-to-TreatPrimary Analysis: Modified Intent-to-Treat

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TITAN-TIMI 34: ConclusionsTITAN-TIMI 34: Conclusions

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

A strategy of early initiation of A strategy of early initiation of eptifibatide in the emergency room eptifibatide in the emergency room prior to primary PCI for ST segment prior to primary PCI for ST segment elevation MI yields superior pre-PCI elevation MI yields superior pre-PCI TIMI frame counts (epicardial flow) and TIMI frame counts (epicardial flow) and superior TIMI myocardial perfusion superior TIMI myocardial perfusion compared to a strategy of initiating compared to a strategy of initiating eptifibatide in the cardiac eptifibatide in the cardiac catheterization laboratorycatheterization laboratory

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TITAN-TIMI 34: Clinical ImplicationsTITAN-TIMI 34: Clinical Implications

© © TIMI 2005. Duplication prohibited by lawTIMI 2005. Duplication prohibited by law

Among patients who are to undergo Among patients who are to undergo primary PCI for STEMI, GP IIbIIIa primary PCI for STEMI, GP IIbIIIa inhibition should be initiated as soon inhibition should be initiated as soon as possible prior to cardiac as possible prior to cardiac catheterization.catheterization.