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Treatment of STEMI in 2011:Treatment of STEMI in 2011:

Management of PatientsManagement of PatientsPresenting to NonPresenting to Non- -PCI CentersPCI Centers

Stephen G. Ellis, M.D.Professor of Medic ine

Direc tor Invasive Servic esCo-Direc tor Card iac Gene Bank

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

How do you tell?How do you tell?

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

Which one?Which one?

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

How highHow highrisk?risk?

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

Who shouldWho shouldget lytics?get lytics?

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI--Less emphasis on difference between DTNLess emphasis on difference between DTNand DTB per seand DTB per se

-- m u ance y cs or presen a on m nm u ance y cs or presen a on m n--Otherwise PCI except for high risk, early presentingOtherwise PCI except for high risk, early presenting

pts with long DTB delay and low risk of bleedingpts with long DTB delay and low risk of bleeding--Kee decision tree sim le thinkinKee decision tree sim le thinkin - ->dela s>dela s

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

Which one?Which one?

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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SSENT IV SSENT IV - - Trial Desi n Trial Desi n ASSENT IV Study Design ASSENT IV Study Design

STEMI patients < 6 hrs, PCI within 1-3 hrsN=4000

Randomization 1:1, Open Label

Clopidogrel only after angiogram when decision for stent implantation is made

Primary PCI

IIb/IIIa investigator discretionPre-treatment with Full Dose TNK followed

by Primary PCI

Primary Endpoint * : Composite of Death or Cardiogenic Shock or Congestive Heart

(clopidogrel if stent)IIb/IIIa bail out only* (clopidogrel if stent)

Failure within 90 Days

* * Used in only 9.6% Used in only 9.6%

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Sto ed on Basis of Mortalit at 30 Da sSto ed on Basis of Mortalit at 30 Da s ASSENT IV Preliminary Data ASSENT IV Preliminary Data

1010

Mortality (%)Mortality (%)

TNK + PCITNK + PCI

88

P = 0.04P = 0.04

44 3.8

22

50/82850/828 32/83532/83500

6.7 vs 5.0% (p=.14) at 90 days6.7 vs 5.0% (p=.14) at 90 days

Van de Werf ESC 2005 18.8 vs 13.7% (p=.006) MACE at 90 days18.8 vs 13.7% (p=.006) MACE at 90 days

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cute MIcute MIPlatelet Activation by FibrinolyticsPlatelet Activation by Fibrinolytics

Normalized Maximal Aggregation RateNormalized Maximal Aggregation Rate

1.51.5 SK

1.01.0

0.50.5

Time (min)Time (min)00 5050 100100 150150 200200 250250

Rudd and Loscalzo, CircRes 90Rudd and Loscalzo, CircRes 90Rabbit model, .05mM ADP as agonistRabbit model, .05mM ADP as agonistSGE; 0802-3, 22

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FINESSE: Stud Desi nFINESSE: Stud Desi n Acute ST Elevation MI (or New LBBB*) within 6h pain onset Acute ST Elevation MI (or New LBBB*) within 6h pain onset

Presenting at Hub or Spoke with estimated time to PCI between 1 and 4 hoursPresenting at Hub or Spoke with estimated time to PCI between 1 and 4 hours

Randomize 1:1:1N=3000 *Only 5U if 75

*LocalizedIMI excluded

PlaceboPlacebo

Reteplase (5U+5U)*Abciximab

PlaceboAbciximab

Transfer To Cath LabASA, unfractionated heparin 40U/kg (max 3000u)

Abciximab Placebo Placebo

. .

Primary PCI with Abciximab Infusion (12 h)

Primary endpoint at 90 days: All-cause mortality, resuscitated VFoccurring > 48H, cardiogenic shock, or readmission/ED visit for CHF

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All Cause Mortalit Throu h 1 Year All Cause Mortalit Throu h 1 Year

7.4%

6.3%.

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FINESSE: 1 Year Mortality byFINESSE: 1 Year Mortality by

All Cause Mortality Through 1 Year

20%

25%

10.0%

15%

c e n t a g e

p=.093

4.6% 4.9%6.1% 6.5%

5%

10% P e

0%

Nonanterior (n=1279) Anterior (n=1173)

Primary PCI with In Lab AbciximabAbciximab Facililated PCI

Abciximab/Reteplase Facilitated PCI

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HORIZONS: ThreeHORIZONS: Three- -Year All Year All- -Cause MortalityCause Mortality

1010Bivalirudin alone (n=1800)Bivalirudin alone (n=1800)

Heparin + GPIIb/IIIa (n=1802)Heparin + GPIIb/IIIa (n=1802)

7.7%7.7%

l i t y ( %

l i t y ( %

77

88

33--yr HR [95%CI]=yr HR [95%CI]=

..

e M o r t

e M o r t

44

55

664.8%

P=0.03P=0.030.75 [0.58, 0.97]0.75 [0.58, 0.97]

l l l l - - C a u C a u 22

33

11--yr HR [95%CI]=yr HR [95%CI]=3.4%

00

00 1212 1515 1818 2121 2424 2727 3030 3333 363633 66 99

. . , .. . , .P=0.04P=0.04

1611161115681568

166016601689168916701670

18001800Bivalirudin aloneBivalirudin alone 1098109818021802 16431643

MonthsMonthsNumber at riskNumber at risk

Heparin+GPIIb/IIIaHeparin+GPIIb/IIIa1633163315931593

1574157415251525 10431043

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Impact of PreImpact of Pre- -randomization Heparin inrandomization Heparin in

--

1010

8.5

Bivalirudin

Heparin + GP IIb/IIa

1010

66

8 7.5

66

8

5.6

7.2

444.8

.

444.6

.

2222

Pre-treatment=

Pre-treatment=

NoPre-treatment

=

NoPre-treatment

=Pre-treatment

=Pre-treatment

=

NoPre-treatment

=

NoPre-treatment

=

Astroulakis Z, Hill JM, Eur Heart J Suppl 2009;11:C13Astroulakis Z, Hill JM, Eur Heart J Suppl 2009;11:C13- -C18C18SGE; 0310-3, 71

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Impact of PreImpact of Pre- -randomization Heparin inrandomization Heparin in

--

1010

8.5

Bivalirudin

Heparin + GP IIb/IIa

1010

66

8 7.5

66

8

5.6

7.2

444.8

.

444.6

.

2222

Pre-treatment=

Pre-treatment=

NoPre-treatment

=

NoPre-treatment

=Pre-treatment

=Pre-treatment

=

NoPre-treatment

=

NoPre-treatment

=

Astroulakis Z, Hill JM, Eur Heart J Suppl 2009;11:C13Astroulakis Z, Hill JM, Eur Heart J Suppl 2009;11:C13- -C18C18SGE; 0310-3, 71

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STEMISTEMIImportance of Early Heparin Administrative/HorizonsImportance of Early Heparin Administrative/Horizons

3.03.0

P = 0.006P = 0.006

Pre Randomization HeparinPre Randomization Heparin

2.02.0

2.52.5. es

No

1.51.5%% P = 0.02P = 0.02AcuteAcuteStentStent

ThrombosisThrombosis

0.50.5

.. . 0.8

BivalirudinBivalirudin Randomized+

RandomizedHe arin + GP I

0.00.0.

Dangas, ACC 2009Dangas, ACC 2009SGE; 0310-3, 72

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Triton TIMI 38 STEMI Triton TIMI 38 STEMI

All ACS/PCIAll ACS/PCIpatientspatients

N=13,608N=13,608 2 patients were missing data2 patients were missing datafor primary or secondaryfor primary or secondaryUA/NSTEMIUA/NSTEMI

STEMI patientsSTEMI patients

pa en spa en sN=10,074N=10,074

Within 14Within 14days for days for

= ,= ,

STEMISTEMI

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STEMI CohortSTEMI Cohort== TRITON TIMI TRITON TIMI- -3838

15

12.4%Clopidogrel

10

n t ( % ) 9.5% 10.0%

HR 0.79-

P e r c e 6.5%

HR 0.68-

. .

P=0.02rasugre

NNT = 42

. .P=0.002 TIMI Major

NonCABG Bleeds Prasugrel 2.4

0

Clopidogrel.

Days From RandomizationMontalescot et al Lancet 2008.Adapted with permission from Antman EM.SGE; 0410-8, 31

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Triton TIMI 38: Stent Thrombosis: Triton TIMI 38: Stent Thrombosis:

3.03.0Stent Thrombosis (%)Stent Thrombosis (%)

2.8%

2.4%

2.02.0

p=0.02RRR=42%p=0.008

RRR=51%

1.0

1.6%1.2%

Clopidogrel

Prasugrel

HR=0.58 (0.360.93)NNT=83

Time (Days)

0.0

Time (Days)

0.00 450300 350 40025020015050 1000 450300 350 40025020015050 100

Montalescot G et al. Lancet 2009;373:723Montalescot G et al. Lancet 2009;373:723 3131SGE; 0411-1, 10

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

ASA, Prasugrel*,ASA, Prasugrel*,heparin, BB, statinsheparin, BB, statins

*May give with PCI*May give with PCI(clopidogrel needs(clopidogrel needsloadinloadin

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

How highHow highrisk?risk?

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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CARESSCARESS--ININ--AMI: Desi n AMI: Desi n

pts for whom primary PCI not readilypts for whom primary PCI not readilyavailableavailable

Comparison, after half doseComparison, after half doserete lase+abciximab between routinerete lase+abciximab between routine

immediate referral for cath/PCI and selectiveimmediate referral for cath/PCI and selectiverescue PCI approach in pts who do notrescue PCI approach in pts who do notqualify for primary angioplastyqualify for primary angioplasty

High risk patients only (Killip class > 2, EFHigh risk patients only (Killip class > 2, EF 15 mm)

Di Mario et al. Lancet 2008;371.559

SGE; 0410-8, 61

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CARESSCARESS--ININ--AMI: Primary Outcome AMI: Primary Outcomeprimary outcome (composite of all cause mortality, reinfarction, & refractory MI within 30 days)occurred significantly less often in the immediate PCI group vs. standard care/rescue PCI group

10.7%

4.4%

HR=0.40 (0.21-0.76)

Di Mario et al. Lancet 2008;371:559.SGE; 0410-8, 64

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Transfer AMI Transfer AMI

Cath/PCI After Lysis: Routine or Rescue?Cath/PCI After Lysis: Routine or Rescue?

1,059 pts STEMI 100, Killip 2- -3 or 3 or RVMl rxd with TenecteplaseRVMl rxd with TenecteplaseRR routine or routine or

0.10

0.150.80.8

-10 -

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Intervention After Fibrinol sisIntervention After Fibrinol sisProbability of death, non-fatal reinfarction, or ischemia-driven revascularization

30

500 Patients

-

20Conservative

intervention.

ST elevation in 2 leads

Number at riskTime since randomization (months)

0 2 4 6 8 10 120

dependency

Randomized to either routine

Intervention 248 230 228 226 223 222 221Conservative 251 225 217 211 208 202 195

Probability of death, non-fatal reinfarction

30

Ischemia only driven cath(20% crossover)

10

20

Conservative

1 end pt: death, MI or ischemia reg revasc at 12months

Number at riskTime since randomization (months)

0 2 4 6 8 10 120

intervention

SGE; 0411-11, 1

Fernandez-Aviles Lancet 04Intervention 248 236 235 232 229 228 227Conservative 251 235 230 226 225 221 217

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Clinical Outcome at 30 DaysClinical Outcome at 30 Days

2525

conservative21%21% RR 0.49 (0.27RR 0.49 (0.27- -0.89)0.89)

1515

invasiveP=0.03P=0.03

--

1010 10%10% 9.8%9.8%

P=0.14P=0.14(%)(%)

55 4.5%4.5%2.3%2.3% 2.2%2.2%

Death, reDeath, re- -MI,MI,stroke, newstroke, new

ischemiaischemia

Death, reDeath, re- -MI,MI,strokestroke

DeathDeath

SGE; 0410-1, 13Bohmer E. JACC 55:102, 2010 n=266 patients > 90 min from FMCBohmer E. JACC 55:102, 2010 n=266 patients > 90 min from FMC- ->PCI, rxd with>PCI, rxd withtenecteplase (not selected for high risk) Invasivetenecteplase (not selected for high risk) Invasive- - PCI (89%) 163 min, Cons (71%)PCI (89%) 163 min, Cons (71%)3 da s after TNK3 da s after TNK

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2009 ACC Guidelines: Triage and Transfer for PCI2009 ACC Guidelines: Triage and Transfer for PCI

All but veryAll but veryLow riskLow risk

SGE; 0410-1, 48FJ Kushner et al., 2009 STEMI Guideline UpdatesFJ Kushner et al., 2009 STEMI Guideline Updates

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STEMI: Summar + ConclusionsSTEMI: Summar + Conclusions

PCI trumps primary lytics exceptPCI trumps primary lytics exceptsx < 90 min if lytics given quickly (ambulance)sx < 90 min if lytics given quickly (ambulance)

very long transfer times (time depends onvery long transfer times (time depends onpa en r s pro epa en r s pro e No role for routine facilitated PCINo role for routine facilitated PCI

,,should be transferred for cath/PCI immediately =>should be transferred for cath/PCI immediately =>pharmacopharmaco- -invasive strategy with adequate antiinvasive strategy with adequate anti- -p a e e erapyp a e e erapy

DAP with prasugrel (except when contraindicated),DAP with prasugrel (except when contraindicated),--

SGE; 1109-9, 32

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STEMI Triage for Non Cath Lab HospitalsSTEMI Triage for Non Cath Lab Hospitals

Final WordFinal Word Have protocol for patient transfer in good weather Have protocol for patient transfer in good weather

and bad (eg helicopter, ground transport) worked outand bad (eg helicopter, ground transport) worked outwith receiving hospital(s)with receiving hospital(s)

os r age pro oco n eos r age pro oco n e-- should be relatively simpleshould be relatively simple-- ,,

that can be given iv push)that can be given iv push)

Post contraindications to lytics alsoPost contraindications to lytics also

SGE; 1109-9, 32