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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


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


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


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




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



65%t-PA + abciximab

77%


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



(30 min angio) (60 min angio) (90 min angio)210 240

Primary angioplasty


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%


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%


0

25

50

75

100

0 30 60 90 120 150




(Transfer Patients in DANAMI 2)(Transfer Patients in DANAMI 2)

TIM

I 3

Flo

w (

%)

TIM

I 3

Flo

w (

%)

Primary angioplasty


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





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:


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


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)


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


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


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


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 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?

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days death

bolus abciximab

abciximab dose reteplase

days urgent pci

primary pci

bolus ufh

hours low dose ufh

death stents