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JP Collet and G Monta l escot for the ARCTIC invest i gators

JP Collet and G Monta l escot for the ARCTIC invest i gators.

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JP Collet and G Monta l escot for the ARCTIC invest i gators

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  1. JPCollet andGMontalescot fortheARCTIC investigators ARCTIC:AssessmentbyadoubleRandomizationofaConventionalantiplateletstrategyversusamonitoring-guidedstrategyfor drug-elutingstentimplantationand,ofTreatmentInterruptionversusContinuationoneyear after stenting–ARCTIC-INTERRUPTION (NCT00827411)

  2. Affiliation/FinancialRelationship: Pr Montalescotreports:research grants tothe institutionor consulting/lecturefeesfromBayer, BMS, Boehringer-Ingelheim,DukeInstitute,Europa, GSK,Iroko, Lead-Up,Novartis, Springer,TIMI group, WebMD,Wolters,AstraZeneca,Biotronik,Eli Lilly,The MedicinesCompany,Medtronic,Menarini, Roche,Sanofi-Aventis,Pfizer,Accumetrics,Abbott Vascular,Daiichi-Sankyo,EliLilly,Fédération Française deCardiologie,Fondationde France, INSERM, Institutde France, Nanosphere,ReCor Medical,Stentys,SociétéFrançaise deCardiologie.

  3. Trialconduct • ACTIONStudy Group(AcademicResearchOrganization,Paris): • AcademicCoordinatingCenter:ACTION-InstituteofCardiology-Pitié- SalpêtrièreHospital,Paris • AcademicSponsor:ACTION-APHP-DRC -St-LouisHospital-Paris • AcademicGlobalTrial Operations:ACTION - URC–LariboisièreHospital,Paris • Funding:ACTION,FondationdeFrance,FondationSGAM,Sanofi-Aventis Group,Cordis,Boston-Scientific,Medtronic • SteeringCommittee:G. Montalescot,JPCollet,G.Cayla,T.Cuisset,S. Elhadad, • G. Rangé,E. Vicaut • Investigationsites: 38 FrenchInterventionCenters

  4. Centersandprincipalinvestigators CHUPitié-Salpêtrière,Paris,DrsMontalescot/Collet HôpitaldelaTimone,Marseille,Dr Cuisset,Dr Bonnet CHdeChartres,Dr Rangé CHUCarémeau,Nîmes,Drs Ledermann/Cayla CHdeLagny,Marne-la-Vallée,DrsElhadad/Cohen CliniqueSainte Clothilde,La Réunion,Dr Pouillot CHClermont-Ferrand, Dr Motreff HôpitalLariboisière,Paris,DrHenry HôpitaldeRangueil,Toulouse,Dr Carrié CHdela RégionAnnecienne,Annecy, Dr Belle CHdeBastia,Dr Boueri HôpitalCardiologiqueAlbertCalmette, Lille,Dr VanBelle GHduCentreAlsace,DrsLhoest/Levai HôpitalNordMarseille, Dr Paganelli CHUJeanMinjoz,Besançon,Dr Bassand Clinique duParc, Castelnau-le-Lez,DrShadfar PolycliniquedeBordeauxCaudéran, Bordeaux,DrCasteigt CHMarieLannelongue, LePlessis-Robinson,Dr Caussin HôpitalFrançoisMitterrand,Pau,DrDelarche HôpitalPasteur, Nice, DrFerrari Clinique duTonkin, Villeurbanne,Dr Champagnac CHU dePoitiers,Dr Christiaens HôpitalArnauddeVilleneuve,Montpellier,DrLeclercq HôpitalCardio-Vasculaire LouisPradel,Lyon,Dr Finet HôpitalSaint-Joseph,Marseille, Dr D’Houdain Cliniquedel’Europe,Amiens,Dr Py Hôpital privéBeauregard, Marseille,Dr Wittenberg CHdeCannes,Drs Tibi/Zemour CHRStrasbourg, Dr Ohlmann HôpitalCochin, Paris,Dr Varenne CHd’Avignon,DrsPansieri/Barney HôpitalCardiologiqueduHaut Lévêque,Pessac,Dr Coste CHLens,Dr Pecheux Clinique del'Orangerie,Strasbourg,Dr Aleil CliniqueNantaise,Nantes,Dr Brunel CHdeCompiègne,DrSayah HôpitalPontchaillou,Rennes,DrLe Breton CHDijon,Dr Cottin

  5. ACSpatients BMSin stablepatients DESinallpatients 1 month 6-12months 1 year

  6. Registriesquoted byguidelines Infavorof prolongedDAPTafter DES 18MonthEventsAfterClopidogrelDiscontinuationat6MonthsStratifiedbyStentType* 24MonthEventsinPatientswho DiscontinuedordidnotDiscontinueClopidogrel at6MonthsStratifiedbyStent P=0.02 P=0.50 %D/MI 73% RRR %D/MI 50%RRR 637 579 N=1,216 EisensteinEL etal,JAMA2007 244 499 417 1,976 *N=3 *N=24 PfistererMetal,J AmCollCardiol2006

  7. ClinicalImpactofExtendedDAPTafterPCI AmetanalysisofRandomizedtrials(n=8231) OddsRation M-HRandom95%CI Death 1.15|0.85,1.54] MyocardialInfarction 0.95[0.66,1.36] StentThrombosis 0.88[0.43,1.81] CerebrovascularAccident 1.51[0.92,2.47] TIMIMajorBleeding 2.64[1.31,5.30] 1/100 1/10 1 ExtendedBetter 10 100 ControlBetter N EnglJMed2010;362:1374–1382 Circulation2012;125:2015–2026 Circulation2012;125:505–513. JAm Coll Cardiol.2012Oct 9;60(15):1340-8. EuropeanHeartJournal2012;33:3078-3087

  8. 2-yearKMPlotsofAny Discontinuation, Interruptionand Disruption (FromtheParis-Registry) 60 Discontinuation Disruption 50 Interruption 40.8% 40 30 20 14.4% 10.5% 10 0 0 6 12 TimefromPCI (months) 18 24 MehranR. etalLancet2013

  9. ARCTICtrialdesign Coronary angiogram Rd 1EP:Death,MI,stroke,stentthrombosis,UR Monitoring Conventional HR= 1.13[0.98-1.29] p= 0. 096 34.6% 31.1% VerifyNowand drug adjustment Standardofcare DES Stent-PCI Stent-PCI VerifyNowand drug adjustment Standardof care 200 0 100 300 12-monthFU

  10. ARCTIC-INTERRUPTIONdesign Coronary angiogram Rd VerifyNowanStandardofcaredrug adjustment Stent-PCI Stent-PCI VerifyNowand Standardof care drug adjustment 12-monthFU Rd#2 DAPT SAPT 6-18moremonthsofFU 1EP: Death,MI,stroke,stentthrombosis,urg.revasc.

  11. ExclusionforRd#2 • Anyichemiceventof theprimaryendpointduringthefirst yearof FU • Anyeventoftheprimarysafetyendpointduringthefirst • yearof FU • AnynewrevascularisationneedingDAPTprolongation • Contraindicationto aspirinwithdrawal: • e.g.HaemorragicGIulcer,aspirinresistance • – Physician’s(or patient’s)decision

  12. FlowChart Rd#1:2440patientsin ARCTIC 1181were excluded Rd#2:1259randomizedbyIVRSoneyear afterstenting 635DAPT*FORITTANALYSIS 624SAPT**FORITTANALYSIS 6-18monthsofFollow-Up death,myocardial infarction,stroke, stentthrombosis or urgent revascularization *Dual AntiplateletTherapy;**Singleantiplatelettherapy

  13. Randomizedvs. Non-Randomized Randomized (n=1259) Non-Randomized (n=1181) 63 64 Age- median 33 40* Diabetes- % 10 14* Prior PAD- % 41 45 PriorPCI -% 7 7 Prior CABG- % 31 33 Protonpumpinhibitors-% 99 95* Drug-elutingstentimplanted-% *p<0.05

  14. DAPTvs. SAPT:Baselinecharacteristics DAPT (n=635) SAPT (n=624) 64 64 Age - median 36 37 Diabetes- % 31 30 Prior MI-% 43 40 PriorPCI-% 7 6 Prior CABG - % 90 90 Clopidogrel-% 10 14 Clopidogrel150 mg- % 8.5 8.5 Prasugrel- % 33 29 Protonpumpinhibitors-% 98 99 Drug-elutingstentimplanted-%

  15. PRUAssessmentonmaintenance therapybeforeRd#2 200 P=ns 200 P=0.014 PRU usingVN-P2Y12Assay PRU usingVN-P2Y12Assay 146.84 143.82 145.31 150 100 50 0 PRU NON-RANDOMIZED ARCTIC-INTERRUPTION DAPT SAPT

  16. Treatmentat last F.U.visit P<0.012 97 100 90 80 70 60 50 40 30 20 10 0 94 P<0.0001 PercentofPatients 71.5 P=0.0019 15.2 5.7 2.2 Clopidogrel Prasugrel Aspirin DAPT SAPT

  17. Primary Endpoint upto18months Death,MI,stroke,stentthrombosis,urgentrevascularization DAPT SAPT ----- EventProbability HR =1.17[0.68-2.03] p= 0.5750 4.3% 3.8% Follow-up(days)

  18. AllischemicEndpoints DAPT SAPT HR [95%CI] P PrimaryEndPoint* 3.8 4.3 1.17[0.68; 2.03] 0.57 StentthrombosisorUrgentRevasc 1.3 1.6 1.30[0.51;3.30] 0.58 Deathor myocardialInfarction -% 2.2 2.7 1.26[0.62;2.55] 0.52 Anydeath-% 1.1 1.4 1.32[0.49;3.55] 0.58 Myocardialinfarction- % 1.4 1.4 1.04[0.41;2.62] 0.94 Stentthrombosis - % 0 0.5 Stroke orTIA- % 0.9 0.6 0.69[0.19;2.44] 0.56 Urgentrevascularization-% 1.3 1.4 1.17[0.45;3.04] 0.74 *Anydeath,Myocardial infarction,stentthrombosis,strokeortransientischemicattack,urgentrevascularization

  19. Key SafetyOutcome Wholepopulation DAPT SAPT HR [95%CI] P 1.1 0.2 Majorbleeding-% 0.073 0.15[0.02;1.20] 0.8 0.3 Minorbleeding-% 0.29 0.41[0.08;2.13] 1.9 0.5 Majororminor bleeding-% 0.035 0.26[0.07;0.91] 1.1 0.2 BARCIIIandV 0.073 0.15[0.02;1.20] STEEPLEdefinitions-MontalescotG,etal.NEnglJMed 2006;355:1006–17

  20. Pre-specifiedsubgroups PRIMARYENDPOINT SECONDARYENDPOINT DAPT Relative risk (95%CI) SAPT P Interaction

  21. ARCTIC-INTERRUPTION Halfofthepatientscould notberandomized1 yearafterstenting Therandomizedpatientswereatlowerrisk 3. NoischemicbenefitofDAPTcontinuationbeyondoneyear SignificantmoremajororminorbleedingswithDAPTcontinuation Findingsconsistentacrosspre-specifiedsubgroupsandwithpriorstudies Slidesavailableatwww.action-coeur.org

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