time to integrilin therapy in acute myocardial infarction
DESCRIPTION
TRANSCRIPT
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
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
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
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
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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
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
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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
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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
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.
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
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
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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
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TITAN-TIMI 34: Baseline CharacteristicsTITAN-TIMI 34: Baseline Characteristics
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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
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
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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
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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
TITAN-TIMI 34: Pre-PCI Flow Throughout HeartTITAN-TIMI 34: Pre-PCI Flow Throughout Heart
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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)
© © 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
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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
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.
TITAN-TIMI 34: Treated as Intended in Protocol Analysis
TITAN-TIMI 34: Treated as Intended in Protocol Analysis
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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
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
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
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)
© © 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
© © 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
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
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.