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Emergent Transfer of Acute Emergent Transfer of Acute MI Patients for Facilitated MI Patients for Facilitated
AngioplastyAngioplastyRationale and DHMC ExperienceRationale and DHMC Experience
Nathaniel Niles, MDNathaniel Niles, MDAssociate Professor of MedicineAssociate Professor of Medicine
Dartmouth-Hitchcock Medical CenterDartmouth-Hitchcock Medical Center
Androscoggin Valley HospitalAndroscoggin Valley Hospital October 7October 7thth 2003 2003
Presumed prognosis: very high Presumed prognosis: very high risk of in-hospital deathrisk of in-hospital death
Treatment goal: Treatment goal: prevent death by restoring prevent death by restoring
coronary blood flowcoronary blood flow
FibrinolyticFibrinolyticTherapyTherapy
Primary/Primary/Facilitated PCIFacilitated PCI
Restore flow to Restore flow to epicardial vesselepicardial vessel
MyocardialMyocardial
perfusionperfusion
Current Management Current Management Goals Goals
for Treating Acute STEMIfor Treating Acute STEMI
OcclusionOcclusion PenetrationPenetration Slow FlowSlow Flow Normal FlowNormal Flow
TIMI 0TIMI 0 TIMI 1TIMI 1 TIMI 2TIMI 2 TIMI 3TIMI 3
9.3%9.3%
6.1%6.1%
3.7%3.7%
p<0.0001 vs TIMI 0/1p<0.0001 vs TIMI 2
p<0.0001 vs TIMI 0/1p<0.0001 vs TIMI 2
P=0.003 vs TIMI 0/1P=0.003 vs TIMI 0/1
Tea
m 2
Tea
m 2
Tea
m 2
Tea
m 2
Tea
m 2
Tea
m 2
Ger
man
Ger
man
Ger
man
Ger
man
Ger
man
Ger
man
GU
ST
O 1
GU
ST
O 1
GU
ST
O 1
GU
ST
O 1
GU
ST
O 1
GU
ST
O 1
TA
M I
1-7
TA
M I
1-7
TA
M I
1-7
TA
M I
1-7
TA
M I
1-7
TA
M I
1-7
TIM
I 1
,45,
10B
TIM
I 1
,45,
10B
TIM
I 1
,45,
10B
TIM
I 1
,45,
10B
TIM
I 1
,45,
10B
TIM
I 1
,45,
10B
CM Gibson 1998 in Acute Coronary SyndromesCM Gibson 1998 in Acute Coronary SyndromesSample Size of Pooled Analysis: 5,498Sample Size of Pooled Analysis: 5,498
0
2
4
6
8
10
12
Epicardial Flow and Mortality OutcomesEpicardial Flow and Mortality OutcomesEpicardial Flow and Mortality OutcomesEpicardial Flow and Mortality Outcomes
GUSTO-I: 90’ TIMI Flow and GUSTO-I: 90’ TIMI Flow and Ventricular FunctionVentricular Function
1822
27
39
0
5
10
15
20
25
30
35
40
TIMI 0 TIMI 1 TIMI 2 TIMI 3
Preservation of Regional Wall Motion at 5-7 daysPreservation of Regional Wall Motion at 5-7 days
% o
f G
roup
% o
f G
roup
p=0.007p=0.007
p=0.001p=0.001
N=N= 171171 6363 212212 284284
The GUSTO Angiographic Investigators. N Engl J Med 1993; 329:1615-1622.The GUSTO Angiographic Investigators. N Engl J Med 1993; 329:1615-1622.
Paradigm for Mechanism of Benefit Paradigm for Mechanism of Benefit of Reperfusion Therapy for AMIof Reperfusion Therapy for AMI
Earlier Myocardial ReperfusionEarlier Myocardial Reperfusion
Limitation of Infarct SizeLimitation of Infarct Size
Better LV FunctionBetter LV Function
Improved SurvivalImproved Survival
60% 60% 57%63%
0%
20%
40%
60%
80%
100%
tPA rPA nPA TNK
ASSENT-2 ResultsASSENT-2 ResultsTNKTNK t-PAt-PA
nn 8,4628,462 8,4888,488DeathsDeaths 521521 524524
6.16%6.16% 6.17%6.17%ICHICH 7979 8080
0.93%0.93% 0.94%0.94%Mod BleedsMod Bleeds 26.0%26.0% 28.1%28.1%TransfusionTransfusion 4.3%4.3% 5.5%5.5%
90-minute TIMI 3 Flow90-minute TIMI 3 Flow
TIMI Flow & Mortality in Recent Lytic TrialsTIMI Flow & Mortality in Recent Lytic Trials——Ceiling of Reperfusion with FibrinolyticsCeiling of Reperfusion with Fibrinolytics
TIMI Flow & Mortality in Recent Lytic TrialsTIMI Flow & Mortality in Recent Lytic Trials——Ceiling of Reperfusion with FibrinolyticsCeiling of Reperfusion with Fibrinolytics
Rationale for Combination Rationale for Combination Therapy For Acute ST Elevation MITherapy For Acute ST Elevation MI
Gibson, Circulation 2001Gibson, Circulation 2001
GP IIb/IIIa Inhibitor + Reduced-Dose LyticGP IIb/IIIa Inhibitor + Reduced-Dose Lytic
ThrombusThrombus
% Stenosis% Stenosis
Luminal DiameterLuminal Diameter
Epicardial PerfusionEpicardial Perfusion
Myocardial PerfusionMyocardial Perfusion
ST ResolutionST Resolution
Reduces Reduces ReinfarctionReinfarction
Facilitates Early PCIFacilitates Early PCI
3945 47
40
49
66 68
54 5662
0
20
40
60
80
Full-Dose LyticFull-Dose Lytic
GP IIb/IIIa +GP IIb/IIIa +½½LyticLytic
% T
IMI 3
Flo
w (
60-9
0 m
ins
)%
TIM
I 3 F
low
(60
-90
min
s)
% T
IMI 3
Flo
w (
60-9
0 m
ins
)%
TIM
I 3 F
low
(60
-90
min
s)
IMPACT-AMIIMPACT-AMI TIMI-14 SPEED TIMI-14 SPEED INTRO-AMI INTRO-AMI INTEGRITYINTEGRITYFull-Dose t-PA +Full-Dose t-PA + ½½ t-PA + t-PA + ½½ r-PA + r-PA + ½½ t-PA + t-PA + ½ Dose TNK½ Dose TNK Eptifibatide Abciximab Abciximab EptifibatideEptifibatide Abciximab Abciximab Eptifibatide EptifibatideEptifibatide
IMPACT-AMIIMPACT-AMI TIMI-14 SPEED TIMI-14 SPEED INTRO-AMI INTRO-AMI INTEGRITYINTEGRITYFull-Dose t-PA +Full-Dose t-PA + ½½ t-PA + t-PA + ½½ r-PA + r-PA + ½½ t-PA + t-PA + ½ Dose TNK½ Dose TNK Eptifibatide Abciximab Abciximab EptifibatideEptifibatide Abciximab Abciximab Eptifibatide EptifibatideEptifibatide
Early TIMI 3 Flow with Early TIMI 3 Flow with Combination TherapyCombination Therapy
00
2020
4040
6060
8080
100100
00 1010 2020 3030 4040 5050 6060 7070 8080 9090 100100Corrected TIMI Frame CountCorrected TIMI Frame Count
100% --- 103 40100% --- 103 40
50% 180/180 154 3450% 180/180 154 34
TNK Eptifibatide NTNK Eptifibatide NTNK Eptifibatide NTNK Eptifibatide NMedian Median CTFCCTFC
%%%%
INTEGRITY TrialINTEGRITY TrialCorrected TIMI Frame CountCorrected TIMI Frame Count
TIMI 14 TIMI 14 Complete (>70%) ST-Segment ResolutionComplete (>70%) ST-Segment Resolution
485556
65
0
20
40
60
80
100Standard r-PA
Reduced dose r-PA + Abciximab
n=54 n=108 n=42 n=82
% of % of PatientsPatients
All PatientsAll Patients Patients with Patients with TIMI 3 flow at 90’TIMI 3 flow at 90’
EHJ 2000;21:1944-53EHJ 2000;21:1944-53
ST ST , lytic eligible, < 6 , lytic eligible, < 6 hh
ST ST , lytic eligible, < 6 , lytic eligible, < 6 hh ASAASAASAASA
No Abciximab
2 x 10 U bolus (30’)Reteplase
Abciximab*
Low Dose Heparin: 60 U/kg bolus followed
by a 7 U/kg/h infusion
1º endpoint: mortality at 30 days2º endpoint: clinical and safety events at 30 days
1º endpoint: mortality at 30 days2º endpoint: clinical and safety events at 30 days
2 x 5 U bolus (30’)Reteplase
Standard Heparin: 5,000 U bolus followed by either
800 U/hr (pts < 80 kg) or 1,000 U/hr (pts > 80 kg) infusion
Lancet 2001; 357:1905-14Lancet 2001; 357:1905-14
GUSTO V - Trial Schematic (n = 16,588)GUSTO V - Trial Schematic (n = 16,588)
Primary Endpoint: 30 Day MortalityPrimary Endpoint: 30 Day Mortality
Lancet. 2001;357:1905-1914.
0
% M
orta
lity 4
6
2
Days0 5 10 15 20 25 30
P=0.43 for superiority
Non-Inferiority RR 0.95(95% CI, 0.84-1.08)
5.6%
Abciximab + Dose Reteplase (n = 8328)
5.9%
Std. Dose Reteplase (n = 8260)
Death30 DaysDeath
30 DaysRe-MI7 DaysRe-MI7 Days
Urgent PCI6 Hrs
Urgent PCI6 Hrs
00
33
66
99% of Patients% of Patients
5.95.95.65.6
3.53.5
2.32.3
8.68.6
5.65.6
Reteplase
Abciximab + Reteplase
OR = 0.95p = 0.43
OR = 0.67p < 0.0001
OR = 0.64p < 0.0001
Lancet, 2001Lancet, 2001Lancet, 2001Lancet, 2001
GUSTO-V: Ischemic GUSTO-V: Ischemic EndpointsEndpoints
UFH IV bolusUFH IV bolusUFH IV bolusUFH IV bolus enoxaparin IV bolusenoxaparin IV bolusLow Dose UFH IV bolusLow Dose UFH IV bolusLow Dose UFH IV bolusLow Dose UFH IV bolus
Wt adj TNK-tPA Wt adj TNK-tPA full-dose IV bolusfull-dose IV bolusWt adj TNK-tPA Wt adj TNK-tPA
full-dose IV bolusfull-dose IV bolusWt adj TNK-tPA
full-dose IV bolusWt adj TNK-tPA
full-dose IV bolusabciximab IV bolusabciximab IV bolusabciximab IV bolusabciximab IV bolus
UFH IV infusion for UFH IV infusion for up to 48 hoursup to 48 hours
UFH IV infusion for UFH IV infusion for up to 48 hoursup to 48 hours
enoxaparin SC injections
every 12 hours up to discharge or
revascularization (max of 7 days)
enoxaparin SC injections
every 12 hours up to discharge or
revascularization (max of 7 days)
Wt adj TNK-tPA Wt adj TNK-tPA half-dose IV bolushalf-dose IV bolusWt adj TNK-tPA Wt adj TNK-tPA
half-dose IV bolushalf-dose IV bolus
abciximab IV infusion abciximab IV infusion for 12 hoursfor 12 hours
abciximab IV infusion abciximab IV infusion for 12 hoursfor 12 hours
Low Dose UFH IV Low Dose UFH IV infusion infusion
for up to 48 hoursfor up to 48 hours
Low Dose UFH IV Low Dose UFH IV infusion infusion
for up to 48 hoursfor up to 48 hours
randomization 1:1:1randomization 1:1:1randomization 1:1:1randomization 1:1:1
ASSENT 3: Trial DesignASSENT 3: Trial DesignASSENT 3: Trial DesignASSENT 3: Trial Designpatients with ST-elevation AMI presenting within 6 hours of patients with ST-elevation AMI presenting within 6 hours of
symptom onsetsymptom onset
Days to Death or Reinfarction or Refractory IschemiaDays to Death or Reinfarction or Refractory IschemiaDays to Death or Reinfarction or Refractory IschemiaDays to Death or Reinfarction or Refractory Ischemia
Pro
babili
ty (
%)
Pro
babili
ty (
%)
Pro
babili
ty (
%)
Pro
babili
ty (
%)
0000
2222
4444
6666
8888
10101010
14141414
12121212
16161616
18181818
20202020
5555 10101010 15151515 20202020 25252525 30303030
Log-rank test: Log-rank test: PP=0.0001=0.0001Log-rank test: Log-rank test: PP=0.0001=0.0001
0000
UnfractionatedUnfractionatedHeparinHeparinUnfractionatedUnfractionatedHeparinHeparin
15.4%
EnoxaparinEnoxaparinEnoxaparinEnoxaparin 11.4%
AbciximabAbciximabAbciximabAbciximab 11.1%
ASSENT 3ASSENT 3Days to Death or Reinfarction or Refractory IschemiaDays to Death or Reinfarction or Refractory Ischemia
10.9 0.9 0.9 0.9
1.7
0.3
0
0.4
0.8
1.2
1.6
2
Full Dose r-PA
1/2 dose r-PA+A
bciximab
Full Dose TN
K1/2 D
ose TNK
+Abcixim
ab
Full Dose TN
K+Enox
Full Dose TN
K1/2 D
ose TNK
+Eptifibatide
N= 8328 8260 2038 2017 2040 118 291N= 8328 8260 2038 2017 2040 118 291
GUSTO VGUSTO V ASSENT IIIASSENT III INTEGRITYINTEGRITY
ICH with ½Dose Lytics + GP ICH with ½Dose Lytics + GP 2b3a Inh.2b3a Inh.Risk compared with Full Dose LyticRisk compared with Full Dose Lytic
ICH with ½Dose Lytics + GP ICH with ½Dose Lytics + GP 2b3a Inh.2b3a Inh.Risk compared with Full Dose LyticRisk compared with Full Dose Lytic
1.1%0.7%
2.1%
2.6%
0%
1%
2%
3%
4%
GUSTO V ASSENT 3
1.1%0.7%
2.1%
2.6%
0%
1%
2%
3%
4%
GUSTO V ASSENT 3
ICH Rates for Age > 75 yrsICH Rates for Age > 75 yrs
p=0.07p=0.07p=0.07p=0.07
p=0.26p=0.26p=0.26p=0.26 lytic lytic + Abciximab lytic lytic + Abciximab
ICH with ½Dose Lytics + ICH with ½Dose Lytics + AbciximabAbciximabIncreased Risk in Elderly PatientsIncreased Risk in Elderly Patients
Mechanical Mechanical Reperfusion for Acute Reperfusion for Acute MIMI• Primary Percutaneous InterventionPrimary Percutaneous Intervention • Meta-analysis →Better than lytics alone (Meta-analysis →Better than lytics alone ( death, death, ICH) ICH)• 10–20% patients unsuitable for PCI10–20% patients unsuitable for PCI• Time to PCI important (delay Time to PCI important (delay CHF, CHF, death) death)• Stents probably better than balloon angioplastyStents probably better than balloon angioplasty
• Facilitated Percutaneous InterventionFacilitated Percutaneous Intervention (=treating the blockage (=treating the blockage pharmacologically before the procedure)pharmacologically before the procedure)• Faster reperfusion before mechanically treating culprit lesionFaster reperfusion before mechanically treating culprit lesion• TIMI 3 flow pre-PCI (TIMI 3 flow pre-PCI ( success, success, EF, EF, death) death)• Extend window of “eligibility” for procedureExtend window of “eligibility” for procedure• ? Optimal adjunctive antithrombotics ? Optimal adjunctive antithrombotics
30-Day 1-Year
p = 0.02p = 0.02 p p << 0.001 0.001 p = 0.014p = 0.014
Weaver WD, JAMA 1997;278Weaver WD, JAMA 1997;278Weaver WD, JAMA 1997;278Weaver WD, JAMA 1997;278
p = 0.001p = 0.001
Primary PCI versus Lysis for ST Primary PCI versus Lysis for ST AMI AMI
balloon"
Primary angioplasty
10% spontaneousreperfusion
73%
"Door-to-
time114 min
0
25
54%"Door-to-needle"
time30 min
t-PA
39%50
75
100
0 30 60 90 120 150
Time from presentation (min)
Reperfusion Strategy Reperfusion Strategy and TIMI-3 Flow Rateand TIMI-3 Flow Rate
(30 min angio) (60 min angio) (90 min angio)
TIM
I 3
Flo
w (
%)
TIM
I 3
Flo
w (
%)
Influence of Ultimate TIMI Flow Influence of Ultimate TIMI Flow on mortalityon mortality
0
2
4
6
8
10
0 20 40 60 80 100Ultimate TIMI 3 Flow (%)
Mor
tali
ty (
%)
1
23
4
5
8
6
77
8
99
ThrombolysisThrombolysis1.1. OccludedOccluded2.2. SK/SQ heparinSK/SQ heparin3.3. SK/t-PASK/t-PA4.4. SK/IV heparinSK/IV heparin5.5. Acc. T-PAAcc. T-PA
Primary PCIPrimary PCI6. GUSTO-2b6. GUSTO-2b7. PAMI-17. PAMI-18. PAMI Reg.8. PAMI Reg.9. PAMI-29. PAMI-2
ExpandedExpanded Paradigm for Mechanism of Paradigm for Mechanism of Benefit of Reperfusion Therapy for AMIBenefit of Reperfusion Therapy for AMI
Earlier Pharmacologic Earlier Pharmacologic Myocardial ReperfusionMyocardial Reperfusion
Limitation of Infarct SizeLimitation of Infarct Size
Better LV FunctionBetter LV Function
Improved SurvivalImproved Survival
Later Mechanical Later Mechanical Myocardial ReperfusionMyocardial Reperfusion
Open Infarct ArteryOpen Infarct Artery
••↓↓Recurrent MIRecurrent MI •• PreventPrevent LV Remodeling LV Remodeling • •Improve Electrical StabilityImprove Electrical Stability • •Provide Source of CollateralsProvide Source of Collaterals
Improved SurvivalImproved Survival
0.2
0.6
1
1.4
1.8
2.2
0-60 61-90 91-120 121-150 151-180 >180
Door-to-Balloon Time (minutes)
P=0.01 P=0.0007 P=0.0003P=NSP=NS
1.14 1.15
1.41
1.62 1.61
N=2,230 5,734 6,616 4,461 2,627 5,412
NRMI-2: Primary PCI Door-to-Balloon time vs. Mortality
Multivariate Adjusted Odds of DeathMultivariate Adjusted Odds of Death
14.6
6.1
N: 64 392/83 200 403 300Random: No No Yes Yes Yes
PCI: PTCA PTCA Stent PTCA StentP: 0.06 0.04 0.03 <0.05 <0.05
26.1
4.5
9.7
3.6
9.2
2
11.2
5.8
0
10
20
30ControlAbciximab
30-d Mortality, MI, Urgent ReV
Primary PCI with Adjunctive GP IIb/IIIaP
erce
nt
Trial EPIC GUSTO-III Neumann RAPPORT ADMIRAL
Herrmann HC. Am J Cardiol. 2000;85:10C-16C.
% o
f p
atie
nts
Stone GW. CADILLAC trial. TCT XI: October 18-22, 2000.
No P valuegiven
Death, re-MI, ischemic TVR, or disabling stroke
0
5
10
15
20
25
15.2
10.9 10.8
19.3
P=0.001
Stenting in AMI - Stenting in AMI - CADILLAC Trial Primary End Point—MACE Through 6 Months
PTCA PTCASTENT STENT
No AbciximabNo Abciximab AbciximabAbciximab
44%44%29%29%
balloon"
Primary angioplasty
10% spontaneousreperfusion
73%
"Door-to-
time114 min
0
25
54%"Door-to-needle"
time30 min
t-PA
39%50
75
100
0 30 60 90 120 150
Time from presentation (min)
Reperfusion Strategy Reperfusion Strategy and TIMI-3 Flow Rateand TIMI-3 Flow Rate
(30 min angio) (60 min angio) (90 min angio)
TIM
I 3
Flo
w (
%)
TIM
I 3
Flo
w (
%)
17% with early Abciximab17% with early Abciximab
95%95%
Average Average “Door-to-“Door-to-
stent” time stent” time 120 min120 min
Primary Stent with early AbciximabPrimary Stent with early Abciximab
65%t-PA + abciximab
77%
0
25
50
75
100
0 30 60 90 120 150
Time from presentation (min)
Reperfusion Strategy Reperfusion Strategy and TIMI-3 Flow Rateand TIMI-3 Flow Rate
65%t-PA + abciximab
77%
(30 min angio) (60 min angio) (90 min angio)
17% with early Abciximab17% with early Abciximab
95%95%
Average Average “Door-to-“Door-to-
stent” time stent” time 120 min120 min
Primary Stent with early AbciximabPrimary Stent with early Abciximab
TIM
I 3
Flo
w (
%)
TIM
I 3
Flo
w (
%)
3%3%1%1% 2%2%
6%6%
4%4%5%5%
9%9%
16%16%
0%0%
5%5%
10%10%
15%15%
20%20%
DeathDeath Re-MIRe-MI UrgentUrgent
RevascRevasc
CompositeComposite
Early PCIEarly PCI
No Early PCINo Early PCI
Facilitated PCI in SPEEDFacilitated PCI in SPEED(All Lytic treated patients)(All Lytic treated patients)
p=1.0p=1.0 p=0.03p=0.03 p < 0.001p < 0.001
Hermann H, JACC 2000Hermann H, JACC 2000Hermann H, JACC 2000Hermann H, JACC 2000
6-Month Mortality6-Month Mortality
4.44.4
2.82.8
0.50.5
0
1
2
3
4
5
TIMI 0-1 TIMI 2 TIMI 3
TIMI Flow Prior to Direct TIMI Flow Prior to Direct PCI:PCI:Pooled PAMI Trials Pooled PAMI Trials (n=2327)(n=2327)
Stone G, Circulation 2001Stone G, Circulation 2001Stone G, Circulation 2001Stone G, Circulation 2001
Potential Benefit with Facilitated Potential Benefit with Facilitated PCI in AMIPCI in AMI
Eptifibatide + 50% TNK Placebo
Primary Endpoint: Death or New or Worsening Primary Endpoint: Death or New or Worsening Severe CHF at 30 daysSevere CHF at 30 days
Primary Endpoint: Death or New or Worsening Primary Endpoint: Death or New or Worsening Severe CHF at 30 daysSevere CHF at 30 days
UFH LMWH LMWH UFH
ST ST AMI AMISx Sx 6 hours 6 hoursLytic EligibleLytic Eligible
Planned Primary PCIPlanned Primary PCI(n = 5640)(n = 5640)
Primary PCIPrimary PCIPrimary PCIPrimary PCI
Eptifibatide + 50% TNK
ADVANCE MIADVANCE MIStudy DesignStudy DesignADVANCE MIADVANCE MIStudy DesignStudy Design
How Should We Manage the How Should We Manage the Transfer Patient with AMI?Transfer Patient with AMI?
PRAGUE StudyPRAGUE Study
AMIAMIST ST or LBBB or LBBB
<6 hrs from onset<6 hrs from onsetOne femoral pulseOne femoral pulse
(n=300)(n=300)Randomized to:Randomized to:
GROUP AGROUP AASA+ASA+
1.5 MU SK1.5 MU SK
GROUP BGROUP BASA +ASA +
1.5 MU SK1.5 MU SKTransportTransport
For cath andFor cath andpossible PCIpossible PCI
GROUP CASA+Heparin
Transport for
primary PCI
DesignDesign
23
15
8
0
5
10
15
20
25
GroupA
GroupB
GroupC
p<0.02
Death/Reinfarction/StrokeDeath/Reinfarction/StrokeAt 30 days (%)At 30 days (%)
ResultsResults
Eur Heart J 2000;21:823-831Eur Heart J 2000;21:823-831
0
25
50
75
100
0 30 60 90 120 150
Reperfusion Strategy Reperfusion Strategy and TIMI-3 Flow Rateand TIMI-3 Flow Rate
Time from presentation (min)
(30 min angio) (60 min angio) (90 min angio)210 240
Primary angioplasty
12% spontaneousreperfusion
94%
Average “Door-Average “Door-to-balloon” time to-balloon” time
for transfer for transfer patientspatients
in PRAGUE in PRAGUE Study: ~100 minStudy: ~100 min
StreptokinaseStreptokinase
31%31%
(Transfer Patients in PRAGUE Study)(Transfer Patients in PRAGUE Study)
TIM
I 3
Flo
w (
%)
TIM
I 3
Flo
w (
%)
High-risk ST elevation MI patients (>4 mm elevation), Sx < 12 hrs5 PCI centers (n=443) and 22 referring hospitals (n=1,129), transfer in < 3 hrs
High-risk ST elevation MI patients (>4 mm elevation), Sx < 12 hrs5 PCI centers (n=443) and 22 referring hospitals (n=1,129), transfer in < 3 hrs
Lytic therapy
Front-loaded tPA 100 mg
(n=782)
Lytic therapy
Front-loaded tPA 100 mg
(n=782)
Death / MI / Stroke at 30 DaysDeath / MI / Stroke at 30 Days
DANAMI-2: Study DesignDANAMI-2: Study DesignDANAMI-2: Study DesignDANAMI-2: Study Design
Primary PCI
with transfer
(n=567)
Primary PCI
with transfer
(n=567)
Primary PCI
without transfer
(n=223)
Primary PCI
without transfer
(n=223)
Stopped early by safety and efficacy committeeStopped early by safety and efficacy committee
0 60 120 180 240
Non-transfer
Transfer
Non-transfer
Transfer Pre-hospital
Pre-hospital
Pre-hospital
Pre-hospital
Door-to-needle
Door-to-needle
In-door-out-doorDoor-to-Balloon
Door-to-Balloon
TransportationTransportation
DANAMI 2:Time From Onset of Symptoms to DANAMI 2:Time From Onset of Symptoms to Treatment Treatment n=1572n=1572
Hospital SiteHospital Site
PC
IP
CI
Thr
ombo
lysi
sT
hrom
boly
sis
www.danami-2.dk/Index.htmwww.danami-2.dk/Index.htm
14%
8%
0%
4%
8%
12%
16%
14%
8%
0%
4%
8%
12%
16%
Dea
th /
MI
/ Str
oke
(%)
Dea
th /
MI
/ Str
oke
(%)
LyticLytic 1° PCI1° PCI
P=0.0003P=0.0003CombinedCombined
DANAMI-2: Primary ResultsDANAMI-2: Primary Results
RRR 45%RRR 45%
14%
9%
0%
4%
8%
12%
16%
14%
9%
0%
4%
8%
12%
16%P=0.002P=0.002
Transfer SitesTransfer Sites
RRR 40%RRR 40%
LyticLytic 1° PCI1° PCI
12%
7%
0%
4%
8%
12%
16%
12%
7%
0%
4%
8%
12%
16%P=0.048P=0.048
Non-Transfer SitesNon-Transfer Sites
RRR 45%RRR 45%
LyticLytic 1° PCI1° PCI
0
25
50
75
100
0 30 60 90 120 150
Reperfusion Strategy Reperfusion Strategy and TIMI-3 Flow Rateand TIMI-3 Flow Rate
Time from presentation (min)
(30 min angio) (60 min angio) (90 min angio)210 240
(Transfer Patients in DANAMI 2)(Transfer Patients in DANAMI 2)
TIM
I 3
Flo
w (
%)
TIM
I 3
Flo
w (
%)
Primary angioplasty
10% spontaneousreperfusion
89%
54%"Door-to-needle"
time30 min
t-PA
39%
““Door-to-Door-to-BalloonBalloon
Time” inTime” inDANAMI 2DANAMI 2
114 min114 min
Transfer for PCI – Emerging Strategy?Transfer for PCI – Emerging Strategy?M
ort
alit
y %
54%
t-PA
39%
t-PA + abciximab 65%
77%
0
25
50
75
100
0 30 60 90 120 150
Reperfusion Strategy Reperfusion Strategy and TIMI-3 Flow Rateand TIMI-3 Flow Rate
Time from presentation (min)
(30 min angio) (60 min angio) (90 min angio)180 210
10% spontaneousreperfusion
95%
“ “Door-to-Door-to-balloon” time balloon” time for transfer for transfer
patientspatients~ 211 min~ 211 min
StreptokinaseStreptokinase
31%31%
(AVH to DHMC Transfer Patients)(AVH to DHMC Transfer Patients)
TIM
I 3
Flo
w (
%)
TIM
I 3
Flo
w (
%)
Primary angioplasty
DHMC AMI DatabaseDHMC AMI Database
DHMC Emergency DeptDHMC Emergency DeptAMI diagnosed:AMI diagnosed:
>30 min of CP and/or>30 min of CP and/orECG with 1mmST elevation or LBBBECG with 1mmST elevation or LBBB
DHMC Emergency DeptDHMC Emergency DeptAMI diagnosed:AMI diagnosed:
>30 min of CP and/or>30 min of CP and/orECG with 1mmST elevation or LBBBECG with 1mmST elevation or LBBB
Oxygen, ASA, heparin, Oxygen, ASA, heparin, beta blocker, nitrates, beta blocker, nitrates,
Morphine, 2 IV lines, treat Morphine, 2 IV lines, treat pain, CHF, shock, pain, CHF, shock,
arrhythmiasarrhythmias
Oxygen, ASA, heparin, Oxygen, ASA, heparin, beta blocker, nitrates, beta blocker, nitrates,
Morphine, 2 IV lines, treat Morphine, 2 IV lines, treat pain, CHF, shock, pain, CHF, shock,
arrhythmiasarrhythmias
Weekday hoursWeekday hoursCall 5-7783,Call 5-7783,
Notify “charge-person”Notify “charge-person”
After hour or weekendsAfter hour or weekends(technician not on site)(technician not on site)
Page Cardiology fellow on callPage Cardiology fellow on call
Administer abciximabAdminister abciximabunless contraindication or unless contraindication or
significant cautionssignificant cautions
Administer abciximabAdminister abciximabunless contraindication or unless contraindication or
significant cautionssignificant cautions
No Cath lab readyNo Cath lab readyCath lab readyCath lab ready
Consent and transport to Catheterization Lab on CallConsent and transport to Catheterization Lab on CallConsent and transport to Catheterization Lab on CallConsent and transport to Catheterization Lab on Call
15 min15 min15 min15 min
25 min25 min 45 min45 min 75 min75 min
55 min55 min 75 min75 min 105 min105 min
Cath Lab timeCath Lab time
Door-to-balloonDoor-to-balloon
Transport to DHMC for Transport to DHMC for potential salvage PCI potential salvage PCI
ASAPASAP
Transport to DHMC Cath Lab Transport to DHMC Cath Lab ASAPASAP
Oxygen, ASA, low dose heparin, beta blocker, nitrates,
Morphine, 2 IV lines, treat pain, CHF, shock, arrhythmias
Non-DHMC Emergency DeptNon-DHMC Emergency DeptAMI diagnosedAMI diagnosed
>30 min of CP and/or>30 min of CP and/orECG with 1mmST elevation or LBBBECG with 1mmST elevation or LBBB
Primary or Possible Planned Rescue/Facilitated PCIPrimary or Possible Planned Rescue/Facilitated PCICall DHMC Cardiology fellow - activate Catheterization LabCall DHMC Cardiology fellow - activate Catheterization Lab Primary Thrombolytic TherapyPrimary Thrombolytic Therapy
Expected transferExpected transfertime to arrival at DHMCtime to arrival at DHMC
(Call-to-table time)(Call-to-table time)
>60 min>60 minAge <75yrsAge <75yrs
<60 min<60 minPrimary PCIPrimary PCI
If en route at 30’If en route at 30’give second bolus of give second bolus of
r-PA 5U IVr-PA 5U IV
Front-loaded t-PAFront-loaded t-PAoror
Double bolus r-PADouble bolus r-PAoror
Single bolus TNK +Single bolus TNK +enoxaparinenoxaparin
Administer Administer abciximababciximab
and r-PA 5U IVBand r-PA 5U IVB
Administer Administer abciximababciximab
Contraindication orContraindication orSignificant Cautions for Significant Cautions for Thrombolytic therapy/Thrombolytic therapy/
abciximababciximab
AMI DatabaseAMI Database
• 1/01-1/03 (1 year backward and 1 1/01-1/03 (1 year backward and 1 year forward from program year forward from program initiation)initiation)
• CardioMac query of all patients CardioMac query of all patients cathed with hx of MI within 24 hrs cathed with hx of MI within 24 hrs
AMI Database - AMI Database - Case Report Case Report FormForm• Emergency Room Emergency Room
• Presentation (Hx/PE)Presentation (Hx/PE)• ECGsECGs• TreatmentTreatment
• Cath LabCath Lab• TIMI FlowTIMI Flow• Timing of reperfusionTiming of reperfusion• InterventionIntervention• Extent of CADExtent of CAD
• Follow-upFollow-up• DeathDeath• StrokeStroke• Recurrent MIRecurrent MI• CHFCHF
325 charts reviewed325 charts reviewed
284 Confirmed caths after recent MI (<24 hours)284 Confirmed caths after recent MI (<24 hours)
228 lytic eligible ECGs and emergent caths228 lytic eligible ECGs and emergent caths
Presented to Presented to DHMC DHMC
Emergency Emergency Room (n=54)Room (n=54)
Presented to Presented to APD or VA APD or VA Emergency Emergency
Room (n=15)Room (n=15)
Presented to Presented to Emergency RoomEmergency Room
Outside area Outside area (n=159)(n=159)
AMI DatabaseAMI Database
DHMC DHMC ER (54)ER (54)
APD or VA APD or VA ER (15)ER (15)
Elsewhere Elsewhere (159)(159)
ER TreatmentER Treatment
Full dose lyticFull dose lytic 00 11 6262
Half dose lyticHalf dose lytic 22 11 4343
No lytic givenNo lytic given 5151 1212 4545
UnknownUnknown 11 11 99
In-hospital OutcomeIn-hospital Outcome
Death (%)Death (%) 8.78.7 11.911.9
Recurrent MI (%)Recurrent MI (%) 5.85.8 6.96.9
Stroke (%)Stroke (%) 0.00.0 0.60.6
CHF (%)CHF (%) 10.110.1 16.416.4
Subseq. Revasc. (%)Subseq. Revasc. (%) 7.27.2 5.05.0
Composite (%)Composite (%) 27.527.5 31.431.4
TIMI Major Bleeding (%)TIMI Major Bleeding (%) 2.92.9 3.83.8
AMI DatabaseAMI Database
211 Patients in Specific Strategy 211 Patients in Specific Strategy SubgroupsSubgroups
63 Presenting to DHMC, APD, VA – Treated with 63 Presenting to DHMC, APD, VA – Treated with Primary PCI, No lyticPrimary PCI, No lytic
60 Presenting elsewhere – Treated with Full dose 60 Presenting elsewhere – Treated with Full dose ThrombolyticThrombolytic
43 Presenting elsewhere – Treated with Half dose 43 Presenting elsewhere – Treated with Half dose ThrombolyticThrombolytic
45 Presenting elsewhere – Not Treated with 45 Presenting elsewhere – Not Treated with ThrombolyticThrombolytic
AMI DatabaseAMI Database
Group
PPCI FD TTx HD TTx No TTx
N 63 60 43 45
Mean Age (years) 61.6 61.0 59.2 61.8
Glycoprotien 2b3a inhibitor in ER (%) 38 3 93 36
ER Presentation to Cath Lab Time (min) 100 337 178 399
Shock on Arrival in Lab (%) 9.7 16.9 7.0 18.6
PCI attempted at cath (%) 98 95 88 98
Outcomes
Death (%) 7.9 10.0 2.3 24.4**
Stroke (%) 0 0 2.3 0
Composite* (%) 28.6 33.3 18.6*** 40.0
TIMI Major Bleeding (%) 3.2 3.3 4.7 2.2
*Any death, recurrent MI, stroke, clinical CHF, repeat revascularization**p<0.05 compared with any other group***p<0.05 compared with group 2 and group 4
AMI DatabaseAMI Database
PPCI HD TTx (FPCI)
p-value
n 63 43
Mean Age (years) 61.6 59.2 ns
Door-to-balloon time (minutes) 100 178 <0.0001
Shock on arrival in cath lab (%) 9.7 7.0 ns
Initial TIMI 2/3 flow (%) 39 73 .001
PCI attempted at cath (%) 98 88 .026
Outcomes
Procedural success (%) 97 97 ns
Ejection fraction (%) 49 52 ns
Death (%) 7.9 2.3 ns
Intracranial hemorrhage (%) 0 2.3 ns
Composite* (%) 28.6 18.6 ns
TIMI Major Bleeding (%) 3.2 4.7 ns
*Any death, recurrent MI, intra-cranial hemorrhage, clinical congestive heart failure, repeat revascularization
AMI DatabaseAMI Database
AMI Dtabase – ConclusionsAMI Dtabase – Conclusions
• Outcomes are not as good as those in RCTsOutcomes are not as good as those in RCTs• Higher risk patients?Higher risk patients?• Quality of Care?Quality of Care?
• Compared with Primary PCI pts, pts treated with a strategy of facilitated PCI (initial Compared with Primary PCI pts, pts treated with a strategy of facilitated PCI (initial HD lytics and GP IIb/IIIa inhibitor) had outcomes at least as favorable despite:HD lytics and GP IIb/IIIa inhibitor) had outcomes at least as favorable despite:• longer transfer times longer transfer times • no increased bleeding problems.no increased bleeding problems.
• In pts with an initial strategy of FD thrombolytic followed by emergent PCI, In pts with an initial strategy of FD thrombolytic followed by emergent PCI, outcomes were less favorable probably because of longer transfer times and outcomes were less favorable probably because of longer transfer times and greater morbidity by the time of cath lab arrival. greater morbidity by the time of cath lab arrival.
• Patients arriving late relative to the start of their MI who are not initially treated with Patients arriving late relative to the start of their MI who are not initially treated with any thrombolytic tended to have the greatest morbidity by the time cath was any thrombolytic tended to have the greatest morbidity by the time cath was initiated and did poorly following PCI. initiated and did poorly following PCI.
• Next StepsNext Steps• Broaden RegistryBroaden Registry
Questions?Questions?