AMI Intervention · Isala klinieken Primary PCI vs Thrombolysis for STEMI Zijlstra et al. Eur Heart J 2002 Boersma et al. EHJ 2006 Mortality at 30 days Pooled Analysis: PCI vs Lytics

IsalaIsala kliniekenklinieken

Harry SuryapranataISALA Klinieken

Hosp. De WeezenlandenZwolle, The Netherlands

Harry SuryapranataHarry SuryapranataISALA KliniekenISALA Klinieken

HospHosp. De . De WeezenlandenWeezenlandenZwolle, The Zwolle, The NetherlandsNetherlands

AMI Interventionin DES Era and Beyond

AMI Interventionin DES Era and Beyond

AngioplastyAngioplasty SummitSummit: April 26, 2007: April 26, 2007


ReperfusionReperfusion TherapyTherapy forfor STEMISTEMI

PCI has never been shown to reduce mortality, except in subsets PCI has never been shown to reduce mortality, except in subsets of pts with AMIof pts with AMI

AMI AMI MortalityMortality in in NetherlandsNetherlands

0

5

10

15

20

25

1950-1960 1960-1970 1980-1990 1990-2000PrePre--CCUCCU CCUCCU

ThrombolysisThrombolysisPrimaryPrimary

PCIPCI

%

ReperfusionReperfusionEraEra

30-Day Mortality

CAPTIM(n=840)

USIC(n=614)

PREMIR(n=1449)

0

2

4

6

8

3.8

4.8

3.3

6.7

5.5

4.4

ThrombolysisThrombolysisPrimaryPrimary PCIPCI 7.9

5.3

PrePre--hospitalhospital ThrombolysisThrombolysis

PCAT(n=6763)

%


PrimaryPrimary PCI PCI vsvs ThrombolysisThrombolysis forfor STEMISTEMI

Boersma et al. EHJ 2006ZijlstraZijlstra et al. et al. EurEur HeartHeart J 2002J 2002

Mortality at 30 daysMortality at 30 daysPooled Analysis: PCI vs Lytics

0

3

6

9

12

EarlyEarly (<2h)(<2h) MediumMedium (2(2--4h)4h) LateLate (>4h)(>4h)

PCIPCILyticsLytics

5.05.03.93.9

6.36.3

4.14.1

12.112.1

4.74.7

%%

TimeTime--delay & 30delay & 30--d Mortalityd Mortality

ThrombolysisThrombolysis

PrimaryPrimary PCIPCI3

5

7

9

11

13

15

00--11 11--22 33--66 66--12h12h22--33

%%

PCAT Meta-Analysis (n=6763)

Are time-delays to P-PCI really NOT that important?


Zwolle Zwolle RandomizedRandomized TrialTrialSymptomSymptom--toto--BalloonBalloon andand OneOne--yearyear MortalityMortality (%)(%)

De Luca et al. JACC 2003De Luca et al. JACC 2003

Every minute delay does count: not only for Every minute delay does count: not only for LyticsLytics, but also for P, but also for P--PCIPCI

0

3

6

9

12

15

4.4 4.7

8.59.7

1.5 1.2 0.80

5.76.3

1213

P = 0.02

P = NSP = NS

P = 0.006

AllAll PatientsPatients LowLow--RiskRisk HighHigh--RiskRisk(n=545)(n=545)(n=1791)(n=1791) (n=1246)(n=1246)

<< 2 h2 h 22--4 h4 h > 6 h> 6 h44--6 h6 h

7.5% increased risk of death for each 30-min delay

Y = 2.86 (Y = 2.86 (++ 1.46) + 0.0045X1.46) + 0.0045X11 + 0.000043X+ 0.000043X22

IschemicIschemic Time Time (min)(min)360360300300240240180180120120606000

1212

1010

88

66

44

22

00p < 0.001p < 0.001

RR death increased by7.5% for each 30-min

Adjusted RR [95% CI]:Adjusted RR [95% CI]:1.0751.075 [1.01[1.01--1.16]1.16]

De Luca, Suryapranata Circulation 2004De Luca, Suryapranata Circulation 2004


Zwolle Zwolle PrePre--hospitalhospital TriageTriage in Transferring in Transferring patientspatients forfor PCIPCI

Symptom-Ambulance 91 min

Ambulance-Admission 49 min

Door-Balloon 38 min

TotalTotal178178’’

ZwolleZwolle PHIATPHIAT protocolprotocol (1998 (1998 -- ))PPrere--HHospitalospital IInfarctnfarct AAngioplastyngioplasty TTriageriage

35 Ambulances + computer35 Ambulances + computer--assisted assisted 1212--lead lead teletele--ECG, using algorithmECG, using algorithm

Identification of a large AMIIdentification of a large AMIAmbulance nurse only, no physicianAmbulance nurse only, no physician

Immediate transfer to Immediate transfer to CathlabCathlabRather than to nearest Hosp/CCU/ERRather than to nearest Hosp/CCU/ER

PCI Centre ZwolleReferral CenterAmbulance Transport

ZwolleZwolle

1.400.000

Amsterdam

Distance Range: 2 - 95 km


Primary PCI for STEMI: Primary PCI for STEMI: Zwolle ExperienceZwolle Experience (1994(1994--2004)2004)

0

1

2

3

4

5

6

7

1994 1996 1998 2000 2002 2004

In-Hospital Mortality (%)

0

5

10

15

20

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Patients > 75 yrs (%)

0

2

4

6

8

10

12

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Hospital Stay (day)

-0,1

0,1

0,3

0,5

0,7

0,9

1,1

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Door-to-Balloon Time (hrs)

0

100

200

300

400

500

600

700

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

Admitted STEMI(n=4732)

0

20

40

60

80

100

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

P C I C A B G C o ns e rv at iv e

Primary PCI

No Lytics used


Routine Routine StentStent vsvs Balloon in a consecutive series of unselected ptsBalloon in a consecutive series of unselected ptsZwolleZwolle--6 6 ““RealReal WorldWorld”” RandomizedRandomized TrialTrial

StentStent BalloonBalloonPostPost--PCI PCI ResultsResults (n=849)(n=849) (n=834)(n=834)

TIMITIMI--3 Post3 Post (%)(%) 8888 8888MBG IIMBG II--IIIIII (%)(%) 8181 8080Distal Distal emboliemboli (%)(%) 1414 1818ComplCompl STST--resres (%)(%) 5656 5454LVEFLVEF (%)(%) 4444 4545LDH Q48hLDH Q48h (U/L)(U/L) 12271227 12861286

0

10

20

30

DeathDeath ReRe--MIMI Death/Death/ReRe--MIMI

TVRTVR MACEMACE

7.17.16.66.68.48.4

6.86.8

141412.412.4

19.619.6

20.720.7

26.326.326.326.626.626.6

%%OneOne--year Clinical Outcomeyear Clinical Outcome

Balloon (n=834)Balloon (n=834)Stent (n=849)Stent (n=849)

Suryapranata et al. Heart 2005Suryapranata et al. Heart 2005

• StentStent doesndoesn’’t improve t improve epiepi--/myo/myo--cardialcardial reperfusion, unlike to reduce mortalityreperfusion, unlike to reduce mortality• StentStent has never been shown to reduce mortality, as compared to balloohas never been shown to reduce mortality, as compared to balloonn


STUDYSTENTING

n/N (%)BALLOON

n/N (%) OR (fixed) 95% CI Weight % OR 95% CI

CADILLAC 28/524 (5.3%) 16/528 (3.0%) 9.23 1.81 [0.97, 3.38] 0.061

CADILLAC 17/512 (3.3%) 28/518 (5.4%) 16.47 0.60 [0.32, 1.11] 1.0FRESCO 1/75 (1.3%) 4/75 (5.3%) 2.42 0.24 [0.03, 2.20] 0.36Jacksch et al 5/231 (2.2%) 7/231 (3.0%) 4.19 0.71 [0.22, 2.26] 0.56PAMI 26/452 (5.8%) 14/448 (3.1%) 8.11 1.89 [0.97, 3.67] 0.056PASTA 3/67 (4.5%) 6/69 (8.7%) 3.46 0.49 [0.12, 2.05] 0.49PSAAMI 4/44 (9.1%) 8/44 (18.2%) 4.45 0.45 [0.12, 1.62] 0.35STENTIM-2 3/101 (3.0%) 2/110 (1.8%) 1.14 1.65 [0.27, 10.1] 0.58

STOPAMI-3 25/305 (8.2%) 28/306 (9.2%) 15.71 0.89 [0.50, 1.56] 0.67STOPAMI-4 7/90 (7.8%) 11/91 (12.1%) 6.21 0.61 [0.23, 1.66] 0.33

ZWOLLE-5 3/112 (2.7%) 4/115 (3.5%) 2.35 0.76 [0.17, 3.49] 1.0ZWOLLE-6 47/785 (6.0%) 45/763 (5.9%) 26.26 1.02 [0.67, 1.55] 0.94

TOTAL (95% CI) 169/3298 (5.1%) 173/3298 (5.2%) 100.00 0.97 [0.78, 1.21] 0.81

STENT BETTERSTENT BETTER BALLOON BETTERBALLOON BETTER

ABCIXIMAB 60/919 (6.5%) 55/925 (5.9%) 31.25 1.10 [0.76, 1.61] 0.6CONTROL 109/2379 (4.6%) 118/2373 (5.0%)

0.1 0.2 0.5 1 2 5 10

68.75 0.92 [0.70, 1.20] 0.5

P value

WITHOUT ABCIXIMAB WITHOUT ABCIXIMAB

WITHWITH ABCIXIMAB ABCIXIMAB

De Luca, Suryapranata et al. JACC 2006De Luca, Suryapranata et al. JACC 2006

12-month MORTALITYMetaMeta--AnalysisAnalysis:: StentingStenting vsvs Balloon Balloon forfor STEMISTEMI (13 (13 RCTRCT’’ss; n=6921); n=6921)


Underlying Risk Profile

Log (OR) for 12-month Mortality

Sten

tBet

ter

| Bal

loon

Bet

ter

.20.16.12.08.040

1.0

0.5

0.0

-0.5

-1.0

-1.5

Beta=Beta=--00.61.61, , P=P=00.034.034

Underlying Risk Profile.10.08.06.04.020

1.5

1.0

0.5

0.0

-0.5

-1.0

-1.5Beta=-0.63, p=0.022

Log (OR) for 30-day Mortality

Sten

tBet

ter

| Bal

loon

Bet

ter

MetaMeta--RegressionRegression AnalysisAnalysis:: StentingStenting vsvs Balloon Balloon forfor AMI AMI (n=6921)(n=6921)

The higher the risk profile, the greater the benefits from The higher the risk profile, the greater the benefits from StentingStentingDe Luca, Suryapranata et al. JACC 2006De Luca, Suryapranata et al. JACC 2006


StudyStudy

DiDi LorenzoLorenzo

BASKETBASKET

HaamuHaamu--StentStent

PASSIONPASSIONSESAMISESAMI

STRATEGYSTRATEGY

TYPHOONTYPHOON

TOTALTOTAL (95% CI)(95% CI)

DESDES BMSBMS%% %%

0.80.84.94.93.73.7

5.35.3

1515

9.79.78.18.1

4.64.66.96.95.65.6

4.84.8 11.611.6

7.67.611.711.720.420.413.413.4

OROR (95% CI)(95% CI)

0.10.1 0.20.2 0.50.5 22 55 101011

FavorsFavors DESDES FavorsFavors BMSBMS

DESDES BMSBMS%% %%

2.52.52.12.19.79.7

4.64.6

55

4.94.95.45.4

1.91.988

2.22.2

3.73.7 4.84.8

6.66.65.45.49.19.12.22.2

OROR (95% CI)(95% CI)

0.10.1 0.20.2 0.50.5 22 55 101011

FavorsFavors DESDES FavorsFavors BMSBMS

TVR TVR @@ 66--12 12 MonthsMonths MortalityMortality @@ 66--12 12 MonthsMonths

MetaMeta--AnalysisAnalysis:: DES DES vsvs BMS BMS forfor STEMISTEMI (n=2360)(n=2360)

No No differencedifference in in StentStent ThrombosisThrombosis (1.2 (1.2 vsvs 1.91.9%%)) oror rere--MIMI (2.3 (2.3 vsvs 2.72.7%%))


RandomizedRandomized Trial: DES Trial: DES vsvs BMS BMS forfor STEMI STEMI @@ 11--year F/Uyear F/U

TYPHOONTYPHOON

StentStent ThrombosisThrombosis: : 3.43.4 vsvs 3.63.6%%

CYPHER (n=355)BMS (n=357)

0

4

8

12

16

Death

2.2 2.2

%

P=NS

MI TLR MACE

1.1 1.4P=NS

3.7

12.6

P < 0.001

5.9

14.6

P < 0.001

0

5

10

15

20

25

Restenosis TLR MACE

P<0.05 P<0.05 P<0.05

%BMS (n=230)CYPHER (n=230)

SESAMISESAMI

SpauldingSpaulding et al. NEJM 2006et al. NEJM 2006 Menichelli et al. EuroPCR 2006

No No differencedifference in in MortalityMortality oror rere--MI MI @@ 11--year F/Uyear F/U


0

10

20

30

P=0.04

P=0.5 P=1 P=0.06

MACEDeath MI TVR

% BMS + AbciximabSES + Tirofiban

STRATEGYSTRATEGYPASSIONPASSION

StentStent ThrombosisThrombosis: : 11%%

0

4

8

12

Death/MI MACE

4.8

6.5

8.7

12.6%

P=NS P=NS

6.27.4

P=NS

TLR

TAXUS (n=309)BMS (n=310)

Laarman et al. NEJM 2006Laarman et al. NEJM 2006 Valgimigli et al. JAMA 2005

RandomizedRandomized Trial: DES Trial: DES vsvs BMS BMS forfor STEMI STEMI @@ 11--year F/Uyear F/U


Pittl et al. WCC 2006

DES DES vsvs BMS BMS forfor STEMI STEMI @@ 66--month F/Umonth F/U

The The safetysafety && efficacyefficacy of DES of DES forfor STEMI STEMI remainremain toto bebe establishedestablished

Kernis SJ et al. Am J Cardiol 2005

DESDES

BMSBMS

Survival (%)P=0.0427P=0.0427

monthmonth

PREMIER RegistryBASKET Trial

0

5

10

15

20

Death Re-MI TVR

P=NS P=NS

P=NS

2.1

5.4

2.84.1

4.9

8.1 7.6

16.7

P=0.053

MACE

BMS (n=74)CYPHER (n=76)TAXUS (n=67)

%%


TheThe HORIZONSHORIZONS TrialTrial

P.I: P.I: GreggGregg W. W. StoneStone

3400 STEMI patients 3400 STEMI patients at 200 International sitesat 200 International sitesAspirin 324 mg + Aspirin 324 mg + ClopidogrelClopidogrel 300 or 600 mg300 or 600 mg

Clinical F/U at 1, 6, and 12 months, then yearly for 5 yearsClinical F/U at 1, 6, and 12 months, then yearly for 5 yearsAngiographic F/U at 13 months: 1500 Angiographic F/U at 13 months: 1500 stentstent randomized ptsrandomized pts

Primary PCIPrimary PCI

1:11:1

Bare metal stentBare metal stent(n~750)(n~750)

3:13:1TAXUS SR stentTAXUS SR stent(n~2250)(n~2250)

UFH + UFH + RoutineRoutineIIb/IIIaIIb/IIIa inhibitorinhibitor

BivalirudinBivalirudin ++BailBail--outout IIb/IIIaIIb/IIIa

Eligible for Eligible for StentingStenting

IsalaIsala kliniekenkliniekenDES for AMI seems to be feasible and even more effective in reducing TVR Safety issue of DES on SAT, particularly in AMI’s, has yet to be established

TheThe CEZARCEZAR TrialTrialCypher vs Taxus drug-Eluting stent: A Zwolle AMI Randomized trial

Interim Interim AnalysisAnalysis as of August 31, 2006as of August 31, 2006 (n=269)(n=269)

MACE MACE @@ TAXUSTAXUS CYPHERCYPHER3030--day F/Uday F/U (n=134)(n=134) (n=135)(n=135)

DeathDeath 22 33ReRe--MIMI 44 33CABGCABG 11 00SAT/TLRSAT/TLR 44 554%

TAXUSTAXUS CYPHERCYPHERBaselineBaseline (n=134)(n=134) (n=135)(n=135)

AgeAge ((meanmean, , yrsyrs)) 6060 6161MaleMale (%)(%) 7272 7070DiabetesDiabetes (%)(%) 1212 1111PrevPrev MI/PCIMI/PCI (%)(%) 99 66


DrugDrug--ElutingEluting StentStent vsvs Bare Bare MetalMetal StentStentLate Late ThromboticThrombotic EventsEvents @@ 11--yr yr afterafter ClopidogrelClopidogrel DiscontinuationDiscontinuation

DES issue on Late Thrombosis: Due to Impaired Re-endothelialization?Spertus et al. Circulation 2006PfistererPfisterer et al. JACC 2006et al. JACC 2006

BASKET LATE

0

2

4

6

8

10

Death and/or MI

Thrombosis Events

TVR

P=0.01

1.3

4.9

1.3

2.6

6.7

4.5

7.9

9.3

MACE

BMS (n=244)DES (n=499)%% %

P<0.001

MortalityMortality @@ 11--yearyear

PREMIER Registry

ClopidogrelDiscontinuation

Continuation


GENOUS GENOUS Endothelial Progenitor CellsEndothelial Progenitor Cells Capture TechnologyCapture Technology

BMS:BMS: Typical neo-intimal response to stent injury

GenousGenous:: Complete healing with mature neo-intima

BrachytherapyBrachytherapy

DrugDrug--Eluting StentEluting Stent

VirmaniVirmani et. al. et. al. HerzHerz 20022002M. M. KutrykKutryk, MD, PhD, St Michael, MD, PhD, St Michael’’s Hospital, Toronto, Canadas Hospital, Toronto, Canada

EEPPCsCs are bone marrow derived, present in the circulating blood, are bone marrow derived, present in the circulating blood, (First described by (First described by AsaharaAsahara in 1996)in 1996)They have the ability to differentiate into mature endothelial cThey have the ability to differentiate into mature endothelial cells, ells, which may which may accelerate Healing process, protect against thrombus, accelerate Healing process, protect against thrombus, and minimize and minimize restenosisrestenosis, with safety profile over current , with safety profile over current DESDES


ZwolleZwolle HEALINGHEALING--AMIAMI StudyStudyA pilot trial on safety A pilot trial on safety && feasibility of feasibility of GenousGenous RR--StentStent for AMI for AMI PrePre--treated with treated with statinstatin, aspirin, , aspirin, andand clopidogrelclopidogrel (for only 30(for only 30--d)d)

ClinicalClinical OutcomeOutcome @@ 3030--dd

CardiacCardiac DeathDeath 11ReRe--MIMI 11**SAT + ReSAT + Re--PCIPCI 11**CABGCABG 33**MACEMACE 44

Baseline Baseline CharacteristicsCharacteristics

AgeAge ((yrsyrs)) 5757 (35(35--81)81)MaleMale 3737 7474%%DiabetesDiabetes 77 1414%%HypercholHyperchol 1313 2626%%HypertensionHypertension 1717 3434%%

As of March 31, 2007 (n=50)

PreliminaryPreliminary ResultsResults

** Same patient due to edge dissectionsSame patient due to edge dissections


•• Routine Routine stentingstenting in in unselectedunselected STEMISTEMI pts does not seem pts does not seem to improve clinical outcome, when compared to balloonto improve clinical outcome, when compared to balloon

•• StentingStenting has never been shown to reduce mortality rate, has never been shown to reduce mortality rate, but it is only associated with a reduction in TVR/TLRbut it is only associated with a reduction in TVR/TLR

•• Although DES for AMI seems to be feasible Although DES for AMI seems to be feasible && effective effective in reducing TVR, safety issue remains to be establishedin reducing TVR, safety issue remains to be established

•• The potential role of The potential role of GenousGenous stentstent for for STEMISTEMI, to further , to further reduce SAT and ISR, is currently being investigatedreduce SAT and ISR, is currently being investigated

CONCLUSIONCONCLUSION

AMI AMI InterventionIntervention in DES Erain DES Era

IsalaIsala kliniekenkliniekenDedicatedDedicated PCI centers PCI centers withwith adequate adequate netnet--workingworking and expertiseand expertise

Reperfusion Therapy for STEMI in the Real World Reperfusion Therapy for STEMI in the Real World How to Extend the Benefits of Early PCI?How to Extend the Benefits of Early PCI?

√√ ReductionReduction in in totaltotal IschemicIschemic Time: Time: PrePre--hospitalhospital triagetriage(home/ambulance)(home/ambulance) forfor earlyearly identificationidentification of a of a largelarge MIMI

√√ ImmediateImmediate transfer of transfer of allall highhigh--riskrisk ptspts forfor primaryprimary PCIPCI

√√ ImproveImprove regionalregional logisticslogistics

√√ FastFast tracktrack in PCI centersin PCI centers

√√ ““The The EarlyEarly The The BetterBetter””““The The HigherHigher The Risk,The Risk,The The GreaterGreater The BenefitThe Benefit””

Cath labCath labPCI centerPCI center

NonNon--PCI PCI clinicclinic

AmbulanceAmbulance

ER/CCUER/CCU


The Golden The Golden HourHour in in CasualtiesCasualties of Warof War

Dominique-Jean Larrey1766 - 1842

1797 Italian Campaign:- Heaviest wounded First- Treatment < 15 minutes- On the spot at front line MASHMASH

(Mobile (Mobile ArmyArmy SurgicalSurgical HospitalHospital))Korea 1951Korea 1951--19531953

Lt. R. Adams Lt. R. Adams CowleyCowley

Documents

AMI Intervention · Isala klinieken Primary PCI vs Thrombolysis for STEMI Zijlstra et al. Eur Heart J 2002 Boersma et al. EHJ 2006 Mortality at 30 days Pooled Analysis: PCI vs Lytics