a magdy when 2 pci after mi

Ahmed Magdy, MD, FACC, FSCAINational Heart Institute, Cairo

Optimizing Optimizing ReperfusionReperfusion for for STEMISTEMI Rapid deliveryRapid delivery of reperfusion therapy is of reperfusion therapy is

essential whether PPCI or thrombolyticsessential whether PPCI or thrombolytics Each of these reperfusion methods has Each of these reperfusion methods has

its its merits and shortcomings.merits and shortcomings. The The idealideal reperfusion strategy would reperfusion strategy would

deliver deliver rapid, complete and rapid, complete and sustained reperfusion with sustained reperfusion with normalization of micro-normalization of micro-vascular flow.vascular flow.

Assessing Reperfusion Options for Assessing Reperfusion Options for Patients with STEMIPatients with STEMI11

STEP 1:STEP 1: Assess Assess time time from symptom onset, from symptom onset, risk of STEMIrisk of STEMI, , risk of risk of thrombolysisthrombolysis, , time for transporttime for transport to PCI lab to PCI lab

STEP 2:STEP 2: Determine whether fibrinolysis or invasive Determine whether fibrinolysis or invasive strategy is preferred*strategy is preferred*

Fibrinolysis preferred if:Fibrinolysis preferred if: Invasive strategy preferred if:Invasive strategy preferred if: Early presentation (<3 hours)Early presentation (<3 hours) Invasive strategy not an optionInvasive strategy not an option Delay to invasive strategyDelay to invasive strategy

Skilled PCI lab with surgical backup Skilled PCI lab with surgical backup availableavailable

High risk (i.e. cardiogenic shock)High risk (i.e. cardiogenic shock) Contraindications to fibrinolysisContraindications to fibrinolysis Late presentation (>3 hours)Late presentation (>3 hours) Diagnosis of STEMI is in doubtDiagnosis of STEMI is in doubt

*If presentation is <3 hours from onset and no delay to an invasive strategy, there is no preference for either strategy

JACC 44: 671, 2004

Patients Transported by EMS After Calling 9-1-1

Onset of STEMI

Symptoms

Call 9

11Cal

l Fas

t

9-1-1 EMS

Dispatch

EMS on-scene•Encourage 12-lead ECG

•Consider prehospital fibrinolytic if capable and EMS-to-needle <

30 min

EM

S T

riag

e P

lan

Not PCICapableHospital

PCICapableHospital

Interhospital

TransferHospital Fibrinolysis:Door-to-needle within<30 min

EMS transport:EMS to Balloon within 90 min

Patient self-transport: Hospital Door-to-Balloon within 90 min

EMS transportEMS on

scene Within 8 min

Dispatch

1 min

Patient

5 min afterSymptom onset

Goals

Total ischemic time: Within 120 min*

* Golden hour = First 60 min Adapted from Panel A Figure 1

Antman et al. JACC 2004;44:676.

Gersh, B. J. et al. JAMA 2005;293:979-986.

1)Time is myocardium 2)Infarct size is outcome

Relationship Between Duration of Symptoms of MI Before Reperfusion Relationship Between Duration of Symptoms of MI Before Reperfusion Therapy, Mortality Reduction, and Extent of Myocardial SalvageTherapy, Mortality Reduction, and Extent of Myocardial Salvage



Modified by collaterals,ischemic preconditioning,myocardial oxygen uptake, other vessels

Gersh, B. J. et al. JAMA 2005;293:979-986.





Modified by collaterals,ischemic preconditioning,myocardial oxygen uptake, other vessels

Symptom onset to hospArrival 2 hr

Thrombolysis given, 2 ½ hr

Symptom onset to balloon3 ½ hrThrombolysis induced reperfusion 3 ½ hr

Importance of Rapid Time toImportance of Rapid Time to Treatment With Treatment With FibrinolysisFibrinolysis in in STEMISTEMI

Time from onset of symptoms to treatment (hours)Time from onset of symptoms to treatment (hours)

Abs

olut

e %

diff

eren

ce

Abs

olut

e %

diff

eren

ce

in m

orta

lity

at 3

5 da

ysin

mor

talit

y at

35

days 3.5% 3.5%

2.5% 2.5%

1.8%1.8% 1.6% 1.6%

0.5% 0.5% 0.00.0

1.01.0

3.03.0

2.02.0

4.04.0

0 – 10 – 1 2 – 32 – 3 4 – 64 – 6 7 – 127 – 12 12 – 2412 – 24

The Fibrinolytics Therapy Trialists’ collaborative group. The Fibrinolytics Therapy Trialists’ collaborative group. LancetLancet. 1994; 343:311. . 1994; 343:311.

PCIPCI In-hospital Mortality In-hospital Mortality vs Door to Balloon Timevs Door to Balloon Time

4.96.1

8

12.2

0

2

4

6

8

10

12

14

Door to Balloon Time (hours)

In-hospDeathRate

0-1.4 1.5-1.9 2.0-2.9 >3.0

N= 2,322

Brodie BR, JACC 47, 2006

N=384 N=493 N=750 N=673

Recent Influences of Recent Influences of PracticePracticeSalvage is Time Salvage is Time Dependant Dependant

Superiority of PPCI over fibrinolysis Superiority of PPCI over fibrinolysis if if Door-to-Balloon Door-to-Balloon completed in a completed in a timely fashiontimely fashion

Acknowledgement that Time Matters in PPCIAcknowledgement that Time Matters in PPCI– Recommendations for time to reperfusion Recommendations for time to reperfusion

updatedupdated

Mortality rates with primary PCI as a function of PCI-related time

delay

P = 0.006

0 20 40 60 80 100

PCI-Related Time Delay (door-to-balloon - door to needle)

Ab

solu

te R

isk D

iffere

nce in

A

bsolu

te R

isk D

iffere

nce in

D

eath

D

eath

(%

)(%

)

-50

510

15

Circle sizes = sample size of the individual study.

Solid line= weighted meta-regression.

Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6

62 min62 min BenefitFavors PCIBenefitFavors PCI

HarmFavors LysisHarmFavors Lysis

For Every 10 min delay to PCI: 1% reduction in mortality difference towards lytics

Causes of Time WasteCauses of Time Waste Many patients are not educated, may Many patients are not educated, may

wait clinic hourswait clinic hours Bias of Initial diagnosisBias of Initial diagnosis Long rush hours, difficult transportLong rush hours, difficult transport Availability of beds in CCUAvailability of beds in CCU Availability of cath labs, ready staff and Availability of cath labs, ready staff and

experienced doctorsexperienced doctors Cost of interventionCost of intervention

Thrombolytics are Frequently Used During Off Hours

PCI post thrombolysis in PCI post thrombolysis in STEMISTEMI

Prehospital TLPrehospital TL+ immediate transfer+ immediate transfer

Rescue PCIRescue PCI for failed TL for failed TL

Immediate post-Immediate post-lysislysis

« facilitated PCI « facilitated PCI »»

<24h post <24h post lysis lysis ESC PCI ESC PCI GL 05GL 05

Delayed PCIDelayed PCI before discharge before discharge

PCI post thrombolysis in PCI post thrombolysis in STEMI:STEMI:

Prehospital TLPrehospital TL+ immediate transfer+ immediate transfer

Rescue PCIRescue PCI for failed TL for failed TL

Immediate post-Immediate post-lysislysis

« facilitated PCI « facilitated PCI »»

<24h post <24h post lysis lysis ESC PCI GL ESC PCI GL 0505

Delayed PCIDelayed PCI before discharge before discharge

CAPTIM

RESCUE, REACT

PACT PRAGUE GRACIA 2 ASSENT-4 FINESSE

SIAM IIIGRACIA 1CAPITAL AMIWESTCARESS

« Open artery hypothesis »OAT SWISSI II

Following Following successfulsuccessful thrombolytic thrombolytic therapy, patients should undergo therapy, patients should undergo early early angiography and PCI of their IRAangiography and PCI of their IRA

PCI post thrombolysis in PCI post thrombolysis in STEMI:STEMI:

Defined: more than 50% reduction in Defined: more than 50% reduction in ST elevation in 60 to 90 min post TL ST elevation in 60 to 90 min post TL RxRx

Defined: less than 24hours post TL Defined: less than 24hours post TL RxRx

PCI postPCI post thrombolysis thrombolysis in STEMI: RATIONALE in STEMI: RATIONALE

1.1. Risk of Risk of reocclusionreocclusion high high

2. Early angiographic 2. Early angiographic risk risk stratificationstratification

3.3. High likelihood of High likelihood of residual complex residual complex stenosisstenosis despite successful TL Rx despite successful TL Rx

Rescue PCI

Impact of TIMI Flow Pre-PCI on Infarct Size

Facilitated Angioplasty

Primary, secondary and bleeding end Primary, secondary and bleeding end points in FINESSEpoints in FINESSE

End pointsEnd points Primary Primary PCI (%) PCI (%)

AbciximaAbciximabb

+PCI%) +PCI%)

(abcixima/(abcixima/

reteplase)reteplase)

-facilitated -facilitated PCI (%) PCI (%)

p, p, combined+ combined+ PCI vs PCI vs primary PCI primary PCI

p, combin p, combin +PCIvs +PCIvs abciximab-abciximab-facilitate facilitate

Primary end Primary end point* point*

10.710.7 10.510.5 9.89.8 NSNS NSNS

All-cause All-cause mortality mortality

4.54.5 5.55.5 5.25.2 NSNS NSNS

ComplicationComplications of MI s of MI

8.98.9 7.57.5 7.47.4 NSNS NSNS

Death Death 4.54.5 5.55.5 5.25.2 NSNS NSNS

TIMI major TIMI major bleeding bleeding

2.62.6 4.14.1 4.84.8 0.0250.025 NSNS

TIMI minor TIMI minor bleeding bleeding

4.34.3 6.06.0 9.79.7 <0.001<0.001 0.006 0.006

(Earlier ) Delayed PCI

OAT Occluded Artery TrialOAT Occluded Artery Trial

OAT Occluded Artery OAT Occluded Artery TrialTrial

Disadvantages of OAT

Comments on CARESSComments on CARESS

Again use of Again use of potent antiplateletpotent antiplatelet agent (abciximab), platelets agent (abciximab), platelets inactivated at time of PCI, (In ASSENT inactivated at time of PCI, (In ASSENT IV < 10% use!!)IV < 10% use!!)

Bleeding reassuring as pts > 75yo Bleeding reassuring as pts > 75yo excludedexcluded

Median time from TL Rx to PCI Median time from TL Rx to PCI 212 212 minmin

Post-Lysis PCI studiesPost-Lysis PCI studies

25.6

50.6

9

21

11.6

24.4

4.1

11.1

0

10

20

30

40

50

60

refractIs/D/MI/TLR

D/MI/Revasc D/MI/UA/stoke refract Is/D/MI

PCI

"Conservative"

GRACIA-1GRACIA-1SIAM IIISIAM III CAPITAL MICAPITAL MI CARESSCARESS

P=0.001 P=0.0008 P=0.04 P=0.001

N=1436N=1436

TTrial of rial of RRoutine outine ANANgioplasty and gioplasty and SStenting after tenting after FFibrinolysis to ibrinolysis to EEnhance nhance RReperfusion in eperfusion in AAcute cute

MMyocardial yocardial IInfarctionnfarction

The TRANSFER-AMI trialThe TRANSFER-AMI trial

Warren J. Cantor, David Fitchett, Bjug Warren J. Cantor, David Fitchett, Bjug Borgundvaag, Michael Heffernan, Eric A. Borgundvaag, Michael Heffernan, Eric A.

Cohen, Laurie J. Morrison, John Ducas, Anatoly Cohen, Laurie J. Morrison, John Ducas, Anatoly Langer, Shamir Mehta, Charles Lazzam, Brian Langer, Shamir Mehta, Charles Lazzam, Brian Schwartz, Vladimir Dzavik, Amparo Casanova, Schwartz, Vladimir Dzavik, Amparo Casanova, Paramjit Singh, Shaun G. Goodman on behalf Paramjit Singh, Shaun G. Goodman on behalf

of the TRANSFER-AMI Investigatorsof the TRANSFER-AMI Investigators

BackgroundBackground Treatment delays can reduce or eliminate Treatment delays can reduce or eliminate

benefits of primary PCIbenefits of primary PCI STEMI pts presenting to non-PCI centres often STEMI pts presenting to non-PCI centres often

cannot undergo primary PCI in timely manner, cannot undergo primary PCI in timely manner, and therefore receive thrombolysisand therefore receive thrombolysis

The role and optimal timing of routine early The role and optimal timing of routine early PCI after fibrinolysis remains controversialPCI after fibrinolysis remains controversial

ObjectiveObjective

To compare: To compare:

Pharmacoinvasive strategy (transfer to PCI Pharmacoinvasive strategy (transfer to PCI centre for routine early PCI within 6 hrs) centre for routine early PCI within 6 hrs) with with

Standard treatment (early transfer only for Standard treatment (early transfer only for failed reperfusion, otherwise cath > 24 failed reperfusion, otherwise cath > 24 hrs) hrs)

for for high-riskhigh-risk STEMI patients receiving STEMI patients receiving thromboysis at thromboysis at non-PCI centresnon-PCI centres..

PCI CentrePCI CentreCath LabCath Lab

CommunityCommunityHospitalHospitalEmergencyEmergencyDepartmentDepartment

Cath / PCI within 6 Cath / PCI within 6 hrs regardless of hrs regardless of

reperfusion statusreperfusion status

Cath and Cath and Rescue PCI Rescue PCI

GP IIb/IIIa GP IIb/IIIa InhibitorInhibitor

TNK + ASA + Heparin / Enoxaparin + TNK + ASA + Heparin / Enoxaparin + ClopidogrelClopidogrel

““PharmacoinvasivePharmacoinvasiveStrategy”Strategy”

UrgentUrgent Transfer to PCI Transfer to PCI CentreCentre Assess chest pain, STAssess chest pain, ST

resolutionresolution at 60-90 minutes after at 60-90 minutes after

randomizationrandomization

‘‘High Risk’ ST Elevation MI within 12 hours of symptom onsetHigh Risk’ ST Elevation MI within 12 hours of symptom onset

Failed Reperfusion*Failed Reperfusion*Successful ReperfusionSuccessful Reperfusion

Elective Cath Elective Cath PCIPCI

> 24 hrs later> 24 hrs later

““Standard Standard Treatment”Treatment”

* ST segment resolution < 50% & persistent chest pain, or hemodynamic instability* ST segment resolution < 50% & persistent chest pain, or hemodynamic instability

Repatriation of stable patients within 24 hrs of PCI

Randomization stratified by age (≤75 vs. > 75) and by enrolling siteRandomization stratified by age (≤75 vs. > 75) and by enrolling site

ProceduresProcedures

Cardiac Cath performed (%)Cardiac Cath performed (%)

Time- TNK to Cath (hrs)Time- TNK to Cath (hrs)

PCI performed (%)PCI performed (%)

Stent used (% of PCI cases)Stent used (% of PCI cases)

Time- TNK to PCI (hrs)Time- TNK to PCI (hrs)

PCI within 6 hrs of TNK (%)PCI within 6 hrs of TNK (%)

PCI within 12 hrs of TNK (%)PCI within 12 hrs of TNK (%)

GP IIb/IIIa inhibitor use (%)GP IIb/IIIa inhibitor use (%)

Time- TNK to GP IIb/IIIa inhib. (hrs) Time- TNK to GP IIb/IIIa inhib. (hrs)

IABP use (%)IABP use (%)

CABG performed (%)CABG performed (%)

Standard Standard

TreatmentTreatment

(n=508)(n=508)8282

27 (4, 69)27 (4, 69)

6262

9898

18 (4, 73)18 (4, 73)

3838

4747

5353

11 (4, 63)11 (4, 63)

66

88

PharmacoinvasivePharmacoinvasive

StrategyStrategy

(n=522)(n=522)9797

3 (2, 4)3 (2, 4)

8484

9898

4 (3, 5)4 (3, 5)

8989

9797

7373

4 (3, 5)4 (3, 5)

77

66

Selected Medications Selected Medications UsedUsed

ASA 1ASA 1stst 6 hrs 6 hrs

Clopidogrel 1Clopidogrel 1stst 6 hrs * 6 hrs *

HeparinHeparin

EnoxaparinEnoxaparin

Beta Blocker 1Beta Blocker 1stst 6 hrs 6 hrs

ASA at dischargeASA at discharge

Clopidogrel at dischargeClopidogrel at discharge

Beta Blocker at dischargeBeta Blocker at discharge

ACE Inhibitor at dischargeACE Inhibitor at discharge

Lipid Lowering at dischargeLipid Lowering at discharge

Standard Standard

TreatmentTreatment

(n=508)(n=508)

9797

6969

5757

5555

6161

8585

7373

7979

7474

8080


StrategyStrategy

(n=522)(n=522)

9898

8787

5757

5151

5555

8585

7979

8181

7373

8181

* p< 0.05* p< 0.05

00

22

44

66

88

1010

1212

1414

1616

1818

00 55 1010 1515 2020 2525 3030

10.610.6

16.616.6

Days from RandomizationDays from Randomization

% of Patients% of Patients

Standard PCI > 24 hrs (n=496)Standard PCI > 24 hrs (n=496)Invasive < 6 hrs (n=508)Invasive < 6 hrs (n=508)

n=496n=496n=508n=508

422422468468

415415466466

415415463463

414414461461

414414460460

412412457457

Primary Endpoint: 30-Day Death, re-MI, Primary Endpoint: 30-Day Death, re-MI, CHF, Severe Recurrent Ischemia, CHF, Severe Recurrent Ischemia,

Shock Shock

OR=0.537 (0.368, 0.783); p=0.0013

Components of Primary Components of Primary EndpointEndpoint

DeathDeath

ReinfarctionReinfarction

Recurrent IschemiaRecurrent Ischemia

Death/MI/IschemiaDeath/MI/Ischemia

New / worsening CHFNew / worsening CHF

Cardiogenic ShockCardiogenic Shock

Standard Standard

TreatmentTreatment

(n=498)(n=498)

3.63.6

6.06.0

2.22.2

11.711.7

5.25.2

2.62.6


StrategyStrategy

(n=512)(n=512)

3.73.7

3.33.3

0.20.2

6.56.5

2.92.9

4.54.5

P-ValueP-Value

0.940.94

0.0440.044

0.0190.019

0.0040.004

0.0690.069

0.110.11

Safety Endpoints - Safety Endpoints - BleedingBleeding

Intracranial hemorrhageIntracranial hemorrhage

TIMI scaleTIMI scale

MajorMajor

Major (non-CABG-Major (non-CABG-related)related)

GUSTO scaleGUSTO scale

ModerateModerate

SevereSevere

Severe (non-CABG-Severe (non-CABG-related)related)

TransfusionsTransfusions

Standard Standard

TreatmentTreatment

(n=498)(n=498)1.21.2

4.64.6

3.23.2

2.22.2

1.41.4

1.21.2

5.55.5


StrategyStrategy

(n=512)(n=512)0.20.2

4.34.3

2.22.2

3.53.5

0.60.6

0.60.6

7.17.1

P-ValueP-Value

0.0660.066

0.880.88

0.330.33

0.260.26

0.220.22

0.340.34

0.310.31

SummarySummary Compared with ‘Standard

Treatment’, a ‘Pharmacoinvasive Strategy’ of routine early PCI within 6 hrs after thrombolysis is associated with a 6% absolute (46% relative) reduction in the composite of death, reinfarction, recurrent ischemia, heart failure and shock

Summary Summary

The pharmacoinvasive strategy is not The pharmacoinvasive strategy is not associated with any increase in associated with any increase in transfusions, severe bleeding or transfusions, severe bleeding or intracranial hemorrhage despite high use intracranial hemorrhage despite high use of GP IIb/IIIa inhibitors during PCIof GP IIb/IIIa inhibitors during PCI

In contrast to older trials, routine early PCI after In contrast to older trials, routine early PCI after thrombolysis using stents and contemporary thrombolysis using stents and contemporary pharmacotherapy is safe and effectivepharmacotherapy is safe and effective– Benefit seen despite high cath/PCI rates Benefit seen despite high cath/PCI rates

in Standard Treatment group (including in Standard Treatment group (including ~40% rescue PCI)~40% rescue PCI)

ConclusionsConclusions For high-risk STEMI patients receiving For high-risk STEMI patients receiving

thrombolysis at non-PCI centres, urgent thrombolysis at non-PCI centres, urgent transfer and PCI within 6 hours is transfer and PCI within 6 hours is associated with significantly less ischemic associated with significantly less ischemic complications and no excess in bleedingcomplications and no excess in bleeding

Transfers to PCI centres should be initiated Transfers to PCI centres should be initiated immediately after thrombolysis without immediately after thrombolysis without waiting to see whether reperfusion is waiting to see whether reperfusion is successfulsuccessful

Regional systems should be developed to Regional systems should be developed to ensure timely transfers of STEMI patients to ensure timely transfers of STEMI patients to PCI centres PCI centres

Results• Early PCI within 6 hrs after thrombolysis was associated with a 6% absolute reduction in the primary study composite endpoint . Standard 16.6% vs Pharmacoinvasive 10.6% (OR = 0.0013 = 0.537 [.368, 0.783]: p = 0.0013 (Figure)

Conclusions• Challenges findings of older studies regarding timing of fibrinolysis and PCI• Pharmacoinvasive strategy was safe and effective•Findings provide important information for shaping future guidelines

16.6

10.6

0

2

4

6

8

10

12

14

16

18

20

16.6

10.6

0

2

4

6

8

10

12

14

16

18

20

TRANSFER-MITrial Design: TRANSFER-MI was a randomized study comparing

pharmacoinvasive strategy (transfer to PCI center for routine early PCI within 6 hrs) with standard treatment (early transfer only for failed reperfusion) for high-risk STEMI patients receiving thrombolysis at non-PCI centers (N=1,060). The primary endpoint was 30-day composite of death, reinfarction, recurrent Ischemia, CHF, shock.

Standard Pharmacoinvasive

30 Day Composite (death, reinfarction, recurrent ischemia,

CHF, shock) OR = 0.537p =0.0013

Kastrani, K et al. Presented at ACC, 2008 @2008, American Heart Association. All rights reserved.

% of pts

InterpretationInterpretation

PCI is the default strategyPCI is the default strategy for STEMI patients for STEMI patients admitted to centers without PCI facilities who admitted to centers without PCI facilities who were initially treated with reteplase, heparin and were initially treated with reteplase, heparin and abciximab, abciximab, transfer for PCItransfer for PCI was associated with was associated with a reduction in the primary endpoint of death, MI a reduction in the primary endpoint of death, MI or refractory ischemia at 30 days compared with or refractory ischemia at 30 days compared with continued medical management with continued medical management with revascularization only performed for rescue PCI. revascularization only performed for rescue PCI.

The message from the two studiesThe message from the two studies that that primary PCI does not need facilitation (FINESSE) primary PCI does not need facilitation (FINESSE) but if already received facilitation by lysis or IIb-but if already received facilitation by lysis or IIb-IIIa antagonists, immediate PCI rather than IIIa antagonists, immediate PCI rather than rescue PCI is better.rescue PCI is better.

PCI for AMI Strategies

In summary: European In summary: European GLGL

Egypt COMBATMI 2010 March 24-26, Cairo Sheraton Hotel

2010

4th. Acute Cardiac Care Course

EGYPT COMBAT MI 2010

Cairo Sheraton, March 24-26, 2010

a magdy when 2 pci after mi

Education