Clinical outcomes of State-of-the-Art percutaneous...
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Clinical outcomes of State-of-the-Art percutaneous coronary revascularisation in patients with de novo three vessel disease. Results of the SYNTAX II Trial. Javier Escaned MD, PhD, FESC Hospital Clínico San Carlos / Madrid / Spain on behalf of the SYNTAX II Investigators.
Transcript of Clinical outcomes of State-of-the-Art percutaneous...
Clinical outcomes of State-of-the-Art percutaneous coronary revascularisation in patients with
de novo three vessel disease.
Results of the SYNTAX II Trial.
Javier Escaned MD, PhD, FESC Hospital Clínico San Carlos / Madrid / Spain on behalf of the SYNTAX II Investigators.
Poten&alconflictsofinterest
Speaker'sname:JavierEscanedIhavethefollowingpoten6alconflictsofinteresttoreport:Speakerateduca6onaleventsandconsultancies:Abbo>,AstraZeneca,Biosensors,BostonScien6fic,Medtronic,OrbusNeich,PhilipsHealthcareTheSYNTAXIIstudywasfundedthroughunrestrictedgrantsfromBostonScien6ficandPhilipsVolcano.
Background• Themanagementofpa6entswith3-vessel
disease(3VD)accordingtoESCguidelinesislargelyinfluencedbytheresultsofthepivotalSYNTAXtrial.
• However,sincethecomple6onofthattrialmajortechnicalandproceduraladvances,influencingPCIoutcomes,havetakenplace:• Newriskstra6fica6ontools.• 2ndgenera6onDES.• Physiology-andimagingPCIguidance.• ImprovedCTOPCItechniques.
WindeckerSetal.EHJ2014;35:2541-619EscanedJetal.EuroInterven6on.2016Jun12;12(2):e224-34
3VDwithaSYNTAXScore>32
3VDwithaSYNTAX
Score23-32
3VDwithaSYNTAXScore>32
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III
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A
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B
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ExtentofCAD PCI CABG
Objec&veoftheSYNTAXIIstudy
Toinves6gateifrecenttechnicalandproceduraldevelopmentsinPCI(incorporatedtoformtheSYNTAXIIstrategy)significantlyinfluenceoutcomesinappropriatelyselectedpa6entswiththree-vessel(3VD)coronaryarterydisease.
ComponentsoftheSYNTAXIIstrategy
• SYNTAX Score II (incorpora6ng clinical and anatomical variables) to guideHeartTeamdecisionsonmyocardialrevascularisa6on.
• Physiology-basedrevascularisa6on(hybriduseofiFRandFFR).• Second genera6on DES (thin strut, biodegradable polymer, everolimus-
elu6ngSynergy™stent[EES]).
• IVUS-guidedop6misa6onofstentdeployment(modifiedMUSICcriteria).
• ContemporaryCTOrevasculariza6ontechniques.
• Guideline-directedmedicaltherapy. EscanedJetal.EuroInterven6on.2016Jun12;12(2):e224-34
Designandeligibility• Mul6center,prospec6ve,single-arm,open-labeltrialofpa6entswithde-
novo3VDwithoutleh-mainsteminvolvement
• InclusioniftheSYNTAXscoreIIrecommendseitherCABGorPCI(equipoisein4-yearmortality)orPCI,irrespec6veofanatomicSYNTAXscore.
• Samplesize:450pa6ents(90%powertoshowsuperiorityintermsofuseof2ndgenera6onEESoverPES+a>ri6on).
• Controlgroup:Matchedpa6entswith3VDfromtheSYNTAXItrialwithaSYNTAXScoreIIshowingequipoisebetweenPCIandCABG.
Studydesign:EscanedJetal.EuroInterven6on.2016Jun12;12(2):e224-34.ClincalTrials.goviden6fier:NCT02015832.
• BelfastHealth&SocialCareTrust,UK• HospitalClínicoSanCarlosIDISSC,Spain• JohnRadcliffeHospital,Oxford,UK• HospitalClinicIProvincialdeBarcelona,Spain• ImperialCollegeHealthcareNHSTrust,UK• SzpitalKliniczny,Poland• HospitalUniversitarioLaPaz,Spain• HospitalClinicoSalamanca,Spain• PapworthHospital,UK• AcademischMedischCentrum,TheNetherlands• LiverpoolHeartandChestHospital,UK• ManchesterRoyalInfirmary,UK• FreemanHospitalNewcastle,UK• ErasmusMC,TheNetherlands• TheRoyalInfirmaryofEdinburgh,UK• HospitalUniversitarioMarquésdeValdecilla,Spain• AmericanHeartofPoland(PAK),Poland• HospitalMeixoeiro,Spain• HospitalPuertadeHierro,Spain• Brighton&SussexUniversityHospitalsNHSTrust,UK• GornoslaskieCentrumMedycnze,Poland• StRaphaelHospital,Poland
Par&cipa&ngsites
*Centerslistedbynumberofenrolledpa6ents
454pa6entsenrolledin22Europeancentres
PrincipalInves&gatorsandStudyChairmen
AdrianBanningMBBSMDJohnRadcliffeHospital,Oxford
UniversityHospitals,UnitedKingdomPrincipalInves&gator
JavierEscanedMDPhDHospitalClínicoSanCarlosIDISCC
Madrid,SpainPrincipalInves&gator
VasimFarooqMBChBPhDManchesterRoyalInfirmaryManchester,UnitedKingdom
DeputyChairman
PatrickW.SerruysMDPhDImperialCollegeLondonLondon,UnitedKingdom
Chairman
Studyflowchart:pa&entinclusionScreeningwithSYNTAXScores(SS)I&II
SSIIfavoursPCI SSIIshowsequipoiseforPCIorCABG SSIIfavoursCABG
HeartTeamDiscussionEquivalentanatomicrevascularisa6onachievable?
Yes No
CABGregistry
Pa6ent“signedoff”byHeartTeamforPCI
InformedConsent
Pa6entincludedinthestudy
Studyflowchart:PCIprocedurePa6entincludedintheSYNTAXIIstudy
iFRinallintendedtotreatstenoses
iFR0.86–0.93
FFR≤0.80
FFR
iFR<0.86 iFR>0.93
StenosistreatedwithSYNERGYTMEES
FFR>0.80
Stenosisnottreated
IVUSop&miza&on
Op&malmedicaltherapywithstrictLDLcontrol(≤1.8mmol/L)
Primaryendpoint:comparisonwithPCI
• Primaryendpoint:Compositeofmajoradversecardiacandcerebrovascularevents(MACCE)atone-yearfollow-up.
• Comparator:PredefinedPCIcohort(n=315)fromtheoriginalSYNTAX-Itrialselectedonthebasisofequipoise4-yearmortalitybetweenCABGandPCI
Exploratoryendpoint:comparisonwithCABG
• Exploratoryendpoint:Compositeofmajoradversecardiacandcerebrovascularevents(MACCE)atone-yearfollow-up.
• Comparator:PredefinedCABGcohort(n=334)fromtheoriginalSYNTAX-Itrialselectedonthebasisofequipoise4-yearmortalitybetweenCABGandPCI.
Baselinecharacteris&cs SYNTAXII(n=454) SYNTAXIPCIarm(n=315) Pvalue
Age(years) 66.7±9.7 66.7±9.1 0.99Male 93.2% 93.0% 0.93BMI(kg/m2) 28.9±4.7 28.2±4.4 0.032DM 30.3% 29.2% 0.75CurrentSmoker 14.7% 17.8% 0.26PreviousMI 12.5% 28.7% <0.001PreviousStroke 5.6% 1.9% 0.010Hypertension 77.0% 73.4% 0.26Hyperlipidemia 77.3% 74.4% 0.35
ClinicalPresenta&on <0.001SilentIschemia 5.5% 13.3% Stableangina 68.8% 61.6% Unstableangina 25.6% 25.1%
SYNTAXII SYNTAXIPCIarm Pvalue
ComponentsoftheSYNTAXScoreIIAge 66.7±9.7 66.7±9.1 0.99Gender(Male) 93.2% 93.0% 0.93
CrClearance(ml/min) 82.0±26.9 87.3±28.5 0.008Ejec6onFrac6on(%) 58.1±8.3 61.8±11.3 <0.001PeripheralVascularDisease 7.7% 9.5% 0.37COPD 10.8% 12.7% 0.42AnatomicSYNTAXScore 20.3±6.4 22.8±8.7 <0.001
SYNTAXScoreII
SYNTAXScoreIIPCI 30.2±8.6 30.6±8.7 0.528
Predicted4-yrmortalityPCI(%) 8.9±8.8% 9.2±8.7% 0.640
SYNTAXScoreIICABG 29.1±10.4 29.1±9.6 1.0
Predicted4-yrmortalityCABG(%) 9.0±9.3 8.5±8.1 0.440
Anatomictargetlesions(n=1559)(3.49lesions/pa6ent)
iFRperformed(n=1150;73.8%)
OnlyFFRperformed(n=27;1.7%)
Lesionsnotassessedwithphysiology
(n=382;24.5%)
Pressurewirecrossingnota>empted/indicated*:221Unabletocrossthelesionwithapressurewire**:127Otherreasons:26
*UseofpressureguidewireinCTOswasnotindicated.**Physiologicalinterroga6onwaspromptedirrespec6veofangiographiclesionseverity.
Physiologicalstenosisinterroga&on
Anatomictargetlesions(n=1559)(3.49lesions/pa6ent)
iFRperformed(n=1150)
iFR<0.86(n=603;52%)
iFR0.86-0.93(n=264;23%)
iFR>0.93(n=283;25%)
Treated(n=600;99.5%)
Treated(n=179;67.8%)
Deferred(n=262;92.6%)
FFR16(2.6%) FFR252(95.4%) FFR41(14.4%)
OnlyFFRperformed(n=27)
Physiologicalstenosisinterroga&on
2,64
4,02
0
1
2
3
4
5
SYNTAXII SYNTAXI
37,2
83,3
0
20
40
60
80
100
SYNTAXII SYNTAXI
ImpactofintracoronaryphysiologyonPCICasesofthree-vesselPCI(%)inSYNTAXIIandSYNTAXI
LesiontreatmentateriFR/FFRinterroga&on(n=1177)
P<0.001 P<0.001
Lesionstreatedperpa&ent(n)inSYNTAXIIandSYNTAXI
PCIdeferred31% PCI
performed69%
2.64
4.02
37.2%
83.3%
SYNTAXII
Treatmentofchronictotalocclusions(CTO)
Success
Failed
CTOPCIproceduralsuccessrateinSYNTAXII:87%
n=94
n=14
SYNTAXIICTOPCI
CTOrevascularisa&oninSYNTAXIIandSYNTAXI
0%
20%
40%
60%
80%
100%
SYNTAXII SYNTAXI
87%
53%
p<0.0001
Post-implanta6onIVUSledtofurtherop6misa6onofthestentedlesionin30.2%.
IVUSnoIVUS
Pa&entlevel
84.1%
15.9%
23.6%
76.4%
Lesionlevel
SYNTAXII IVUSuseinSYNTAXIIandSYNTAXI(pa&entlevel,%ofcases)
Useofintravascularultrasound(IVUS)
84.1%
p<0.0001
0%
20%
40%
60%
80%
100%
SYNTAXII SYNTAXI
84.1%
4.8%
Oneyearfollowupresults
ComparisonwithPCI
SYNTAXIPCI
SYNTAXII
Primaryendpoint:MACCE
10.6%
17.4%HR0.58(95%CI0.39-0.85),p=0.006
All-causedeath
2.0%
2.9%
HR0.69(95%CI0.27-1.73),p=0.43
Myocardialinfarc&on
1.4%
4.8%
HR0.27(95%CI0.11-0.70),p=0.007
Stroke
0.4%0.7%
HR0.69(95%CI0.10-4.89),p=0.71
Anyrepeatrevascularisa&on
8.2%
13.7%HR0.57(95%CI0.37-0.90),p=0.015
Definitestentthrombosis
3.8%
HR0.26(95%CI0.0.7-0.97),p=0.045
0.7%
2.7%
OneyearfollowupresultsComparisonwithCABG
ExploratoryEnd-Point:MACCEPCIvs.CABG
CABG
10.6%
11.2%
HR0.91(95%CI0.59-1.41),p=0.684P<0.001fornon-inferiority*
*Non-inferioritymarginof5%withaone-sidedalphaof5%
MACCESYNTAXIIandSYNTAXIPCI/CABGVs.PCIHazardra6o,0.58(95%CI0.39-0.85)
p-value=0.006
SYNTAXIPCI
SYNTAXII
SYNTAXICABG
10.6%
11.2%
17.4%
Oneyearfollowupresults
InfluenceofanatomicSSonMACCE
SYNTAXIIMACCEinSSI≤22and>22
HR0.26(95%CI0.0.7-0.97),p=0.045
SS≤22
SS>22
SYNTAXIIpa6entsonly
SYNTAXSCORE≤22SYNTAXSCORE>22
Conclusions(I)
• Inpa6entswith3VDtheuseoftheSYNTAX-IIstrategywasassociatedwithimprovedclinicaloutcomesatoneyear,comparedtomatchedpa6entstreatedpercutaneouslyintheoriginalSYNTAX-Itrial.
• Theone-yearexploratorycomparisonbetweenSYNTAXIIandmatchedCABGpa6entsfromtheoriginalSYNTAX-Itrialsuggestsnon-inferiorityofPCIwhentheSYNTAX-IIstrategyisfollowed.
Conclusions(II)
• ComparedtoSYNTAXI,contemporarystate-of-artPCIinSYNTAXIIledtosignificantlyfewerlesionstreatedwithPCI,andsignificantlyhighersuccessratesinCTOrevascularisa6on.
• One-year outcomes of pa6ents with SYNTAX score >22, treated withPCIusing the SYNTAX score II risk stra6fica6on,were similar to thoseobservedinpa6entswithlowanatomicalrisk(SYNTAXscore≤22).
PrincipalInves&gatorsPIs:ABanning,JEscanedStudyChairman:PWSerruysDeputyChairman:VFarooqCo-PIs:APKappetein,DTaggart(Surgeons)
SteeringCommiueeABanning,JEscaned,VFarooq,APKappetein,PWSerruys,DTaggart,GAvanEs
SponsorECRI-EuropeanCardiovascularResearchIns6tute
GrantgiversVolcanoandBostonScien6fic
Data&SafetyMonitoringBoardFWMohr,KOldroyd,JTijssen
ClinicalEventsCommiueeJPHerrman,EMcFadden,VThijs,PVranckx
ClinicalResearchOrganiza&onCardialysisBV,Ro>erdam,TheNetherlandsTrialManager:S.LeeflangSta6s6cs:TdeVries,C.Collet,R.Cavalcante
CoreLaboratoryCoronaryphysiology:N.RyanIVUS:G.DeMariaCoronaryCTA:C.Collet,Y.Miyazaki
SYNTAXIItrialorganisa&on
Thankyouforyoura0en1on
PublishedonlinetodayinEHJ(OpenAccess)
academic.oup.com/eurheartjdoi:10.1093/eurheartj/ehx512
Backupslides
BelfastHealth&SocialCareTrustSimonWalsh 70
HospitalClinicoSanCarlosJavierEscaned 50
JohnRadcliffeHospitalAdrianBanning 35
HospitalClinicIProvincialManelSabaté 32
ImperialCollegeHealthcareJus6nDavies 27
HolyTransfigura6onHospitalMaciejLesiak 20
HospitalUniversitarioLaPazRaulMoreno 20
HospitalClinicoSalamancaIgnacioCruz 20
PapworthHospitalNickWest 20
AcademischMedischCentrumJanPiek 20
LiverpoolHeartandChestHospitalClareAppleby&RodStables 19
ManchesterRoyalInfirmaryFarzinFath-Ordoubadi&VasimFarooq 19
FreemanHospitalNewcastleAzfarZaman 19
ErasmusMedicalCenterNicolasvanMieghem 16
TheRoyalInfirmaryofEdinburghNealUren 15
HospitalUniversitarioValdecillaJavierZueco 12
AmericanHeartofPoland(PAK),PawelBuszman 10
HospitalMeixoeiroAndresIñiguez
8
HospitalPuertadeHierroJavierGoicolea 8
Brighton&SussexUniversityHospitalsDavidHildick-Smith 6
GornoslaskieCentrumMedycnze,AndrzejOchala 4
StRaphaelHospitalDariuszDudek 3
Centres,siteinves&gatorsandenrolledpa&ents
Defini&ons• MACCE:All-causedeath,stroke,anymyocardialinfarc6on(MI)orany
revascularisa6on.
• PeriproceduralMI:CK-MB≥5xULN(orTn≥35ULNifCK-MBnotavailable)andnewpathologicalQ-wavesintheECGwithin7dayspostPCI.
• SpontaneousMI:NewQ-wavesoroneplasmalevelofCK-MB5xULN(orTn≥35ULNifCK-MBnotavailable)inthecontextofclinicalsyndromeconsistentwithACS.
• StentThrombosis:AccordingtotheAcademicResearchConsor6um.
SYNTAXII SYNTAXIPCIarm Pvalue
Aspirin
Atdischarge 99.8%(448/449) 96.2%(302/314) <0.001
At1Year 95.6%(413/432) 92.1%(278/302) 0.046
P2Y12inhibitor
Atdischarge 99.3%(446/449) 98.4%(309/314) 0.234
Clopidogrel 66.8%(298/446) N/A
Prasugrel 4.5%(20/446) N/A
Ticagrelor 28.7%(128/446) N/A
At1Year 61.8%(267/432) 72.2%(218/302) 0.0034
Beta-blockeratdischarge 75.7%(339/448) 77.1%(242/314) 0.6550
Sta&natdischarge 97.3%(437/449) 85.4%(268/314) <0.001
Medicaltherapy
SYNTAXII SYNTAXIPCIarm Pvalue
Stentsperpa&ent 3.78±1.92(440) 5.19±2.04(308) <0.001
Stentsperlesion 1.43±0.76(1165) 1.28±0.65(1251) <0.001
Meanstentlength(perstent,mm) 24.43±9.18(1663) 18.82±7.04(1599) <0.001
Totalstentlength(perpa&ent,mm) 92.32±52.78(440) 97.71±43.66(308) 0.13
Useofcoronarystents
SYNTAXTrial903pa6entsrandomisedtoPCI
546pa6entswith3VDSYNTAXScoreIIcalculated
315pa6ents
SYNTAX-IPCIreferencearm
357pa6entswithLehMainDiseaseexcluded
231pa6entsexcluded:SYNTAXScoreIIdidnotshowequipoiseforCABGandPCI
Selec&onoftheSYNTAXIPCIReferenceArm
SYNTAXTrial897pa6entsrandomisedtoCABG
549pa6entswith3VDSYNTAXScoreIIcalculated
334pa6ents
SYNTAX-ICABGreferencearm
348pa6entswithLehMainDiseaseexcluded
215pa6entsexcluded:SYNTAXScoreIIdidnotshowequipoiseforCABGandPCI
Selec&onoftheSYNTAXICABGReferenceArm
