This is a repository copy of Comparison of P2Y12 inhibitors for mortality and stent thrombosis in patients with acute coronary syndromes: Single center study of 10 793 consecutive ‘real-world’ patients.
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Version: Accepted Version
Article:
Gosling, R., Yazdani, M., Parviz, Y. et al. (5 more authors) (2017) Comparison of P2Y12 inhibitors for mortality and stent thrombosis in patients with acute coronary syndromes: Single center study of 10 793 consecutive ‘real-world’ patients. Platelets. ISSN 0953-7104
https://doi.org/10.1080/09537104.2017.1280601
This is an Accepted Manuscript of an article published by Taylor & Francis in Platelets on 07/03/2017, available online: http://www.tandfonline.com/10.1080/09537104.2017.1280601.
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1
ComparisonofP2Y12inhibitorsformortalityandstentthrombosisinpatientswithacute
coronarysyndromes:singlecentrestudyof10,793consecutive‘real-world’patients
Authors:RebeccaGosling1,2,MominaYazdani
2,YasirParviz
1,IanRHall
1,EverDGrech
1,
JulianPGunn1,2,RobertFStorey
1,2,JavaidIqbal
1
Authors’affiliations:
1SouthYorkshireCardiothoracicCentre,NorthernGeneralHospital,Sheffield,UK
2DepartmentofInfection,ImmunityandCardiovascularDisease,UniversityofSheffield,UK
RunningTitle:ComparisonofP2Y12inhibitorsinACSpatients
Keywords:acutecoronarysyndromes,clopidogrel,ticagrelor,prasugrel,percutaneous
coronaryintervention,stentthrombosis
CorrespondingAuthor:
ProfessorRobertF.Storey,
CardiovascularResearchUnit,
CentreforBiomedicalResearch,
NorthernGeneralHospital,
HerriesRoad,Sheffield,S57AU,UnitedKingdom
Tel:+441142159554
Fax:+441142711863
Email:[email protected]
2
ABSTRACT
Threeoral platelet P2Y12 inhibitors, clopidogrel, prasugrel and ticagrelor, are available for
reducing the risk of cardiovascular death and stent thrombosis in patients with acute
coronarysyndromes(ACS).Wesoughttocomparetheefficacyoftheseantiplateletdrugsin
contemporarypractice.
Datawerecollectedfor10,793consecutiveACSpatientsundergoingcoronaryangiography
at Sheffield, UK (2009-2015). Since prasugrel use was mostly restricted to the STEMI
subgroup,clopidogrelandticagrelorwerecomparedforallACSpatientsandallthreeagents
were compared in the STEMI subgroup. Differences in outcomes were evaluated at 12
monthsbyKMcurvesandlog-ranktestafteradjustmentforindependentriskfactors.
Of 10,793 patients with ACS (36% STEMI), 43% (4653) received clopidogrel, 11% (1223)
prasugreland46%(4917)ticagrelor,withaspirinforall.Intheoverallgroup,ticagrelorwas
associatedwithlowerall-causemortalitycomparedwithclopidogrel(adjustedhazardratio
(adjHR)0.82,95%confidenceintervals(CI)0.71-0.96,p=0.01).IntheSTEMIsubgroup,both
prasugrelandticagrelorwereassociatedwithalowermortalitycomparedwithclopidogrel
(prasugrelvsclopidogrel:adjHR0.65,CI0.48-0.89,p=0.007;ticagrelorvsclopidogrel:adjHR
0.70, CI 0.61-0.99, p = 0.05). Of the 7,595 patients who underwent PCI, 78 (1.0%) had
definite stent thrombosis by 12 months. Patients treated with ticagrelor had a lower
incidence of definite stent thrombosis compared with clopidogrel (0.6% vs. 1.1%; adjHR
0.51, CI 0.29-0.89, p=0.03). In the STEMI subgroup, there was no significant difference
betweenthethreegroups(ticagrelor1.0%,clopidogrel=1.5%,prasugrel=1.6%;p=0.29).
In conclusion, ticagrelor was superior to clopidogrel for reduction of both mortality and
stent thrombosis in unselected invasively-managed ACS patients. In STEMI patients, both
3
ticagrelor and prasugrelwere associatedwith lowermortality comparedwith clopidogrel
buttherewasnosignificantdifferenceintheincidenceofstentthrombosis.
4
INTRODUCTION
Antiplateletagentsarethemainstayoftreatmentforpatientswithacutecoronary
syndromes(ACS)[1].ThemajorityofpatientswithACSundergocoronaryrevascularization
withpercutaneouscoronaryintervention(PCI)or,lessfrequently,coronaryarterybypass
graftsurgery(CABG)[2,3].Antiplatelettherapyisvitalinthesepatientstopreventfuture
ischaemiceventsand,inPCI-treatedpatients,stentthrombosis[4-8].Thechoiceof
antiplateletagentsforpatientswithACS,especiallythosewithST-segmentelevation
myocardialinfarction(STEMI),remainsdebatable.Itisrecommendedthatallthesepatients
shouldreceivedualantiplatelettherapyforatleast12months[1].Aspirinshouldbe
continuedindefinitelyandlowdose(75-100mgdaily)ispreferredoverhigherdoses.
Clopidogrel,aP2Y12inhibitor,wasthecommonlyused2ndantiplateletagentinthelast
decade.However,itisapro-drugwhichrequireshepaticactivationbythecytochromeP450
systemandsomepatientsproduceineffectivelevelsofactivemetaboliteleadingtopoor
pharmacodynamicresponseor‘resistance’[9].Consequently,newerP2Y12inhibitors,
prasugrelandticagrelor,havebeendevelopedinrecentyears[9].Prasugreltherapy,
comparedwithclopidogrel,inACSpatientsundergoingPCIhassignificantlyreducedratesof
ischaemicevents,includingstentthrombosis,butwithanincreasedriskofbleedingandno
significanteffecton1-yearmortality[10].Ticagrelor,anon-thienopyridineP2Y12inhibitor,is
anactivedrug,which,followingintestinalabsorption,canrapidlyachieveadequatelevelsof
plateletinhibition.ThePLATOtrialhasshownthatticagrelorreduces1-yearmortalityin
patientswithACS,comparedwithclopidogrel[11].InPLATO,therewasnodifferencein
CABG-relatedbleedingwithticagrelorcomparedwithclopidogrelbuttherelativeincreasein
non-CABG-relatedbleeding,includingthosemanagedwithplannedinvasivestrategy,was
similartothatseenpreviouslywithprasugrel[11,12].However,thereisverylimiteddataon
5
comparisonofnewerP2Y12inhibitorswithclopidogrelinunselectedACSpatients[13].
Furthermore,onlyoneclinicaltrialwithamodestsamplesize(1230patients)hasdirectly
comparedprasugrelwithticagrelorandthishasshownnodifferenceinoutcomes,althoughit
wasterminatedearlyforfutility[14],andtheresultsoffurthercomparativeefficacystudies
areawaited[15].Weaimedtoinvestigatetheeffectoftheintroductionofprasugreland
ticagreloronall-causemortalityandstentthrombosisinthislargesingle-centre,all-comers
registry.
METHODS
Studydesignandpopulation
Datawerecollectedprospectivelyforconsecutivepatientsattendingthecardiac
catheterizationlaboratoryofSouthYorkshireCardiothoracicCentreandundergoing
coronaryangiographybetweenJan2009andJune2015forthemanagementofACS.This
centreistheonlyoneprovidingaPCIandCABGservicetothepopulationinandaround
Sheffield,atotalof1.8millionpeople.ForpatientsundergoingPCI,theprocedureand
adjunctivepharmacotherapywasatthediscretionoftheoperator,butadheredtorelevant
local,national,andinternationalguidelines.Consequently,therewasagradualevolutionof
treatmentduringthecourseofthestudyfromuseofclopidogrelastheonlyP2Y12inhibitor
in2009tointroductionoftheoptionofprasugrelin2010,predominantlyforSTEMI,
followedbytheintroductionofticagrelorasfirst-linetherapyinFebruary2012,accordingto
ourpreviouslypublishedprotocolsthatincludedtheprescriptionofhigh-intensitystatin
therapy,angiotensinpathwayinhibitorsandbeta-blockersthroughoutthestudyperiod
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[16].Ofparticularnote,dualantiplatelettherapyfor12monthsforallACSpatientswasthe
defaultapproachthroughoutthestudyperiod.After12months,patientswereprescribed
aspirinindefinitelyandso,tostudytheimpactofdualantiplatelettherapyonclinical
outcomes,follow-upwaslimitedto12months.Dataonadherenceandswitchingof
antiplatelettherapywerenotcollectedandthereforeouranalysiswasbasedonthe
intentiontotreatpatientswithdualantiplatelettherapyfor12months.Thegroupswere
definedaspertheantiplateletagentprescribedonadmissiontothecatheterlaboratory.
Anypatientwhohadaneventwhilstinhospitalresultinginachangeofantiplateletwere
definedaspertheoriginalantiplateletprescribed.Intra-proceduralunfractionatedheparin,
andnotbivalirudin,wasthedefaultanticoagulationtherapy,alongwithselectiveuseofa
glycoproteinIIb/IIIainhibitor,attheoperators’discretion.Allpatientsweretreatedwith2nd
generationdrug-elutingstentsorbare-metalstents,attheoperators’discretion.Therewere
noexclusioncriteria.TherewasincreasingprovisionofaprimaryPCIservicetothe
populationduringthecourseofthestudy,accountingforahigherproportionofpatients
withSTEMIinthelateryears.
DataCollection
Demographic,clinical,andangiographicdatawerecollectedprospectively.Renalfailurewas
definedascreatininelevelof>200μmol/Landcardiogenicshockassystolicbloodpressure
<100mmHgalongwithsignsorsymptomsofhypoperfusion.Theoutcomedatawere
collectedusingthenationalmortalitydatabaseandthehospitalelectronicdatabaseand
patientrecordsforSouthYorkshireCardiothoracicCentre.Otherpatientrecordswerenot
availableforthisanalysisandsowewerenotabletoassessnon-fatalischaemicand
bleedingoutcomes.TheAcademicResearchConsortium(ARC)criteriawereusedtodefine
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definitestentthrombosis[17]andourdatawerebasedontheassumptionthatsurvivorsof
stentthrombosiswouldpresentorbereferredbacktoourcatheterlaboratorysincethisis
theonlyPCIcentrefortheregionandtherewasnochangeinthisarrangementduringthe
courseofthedatacollection.Thecaseswereadjudicatedbyreviewoftheangiographyfilms
bytwocardiologistsindependentlyand,incasesofdifferenceofopinion,byathird
cardiologistasareferee.
Dataanalysis
Dataarepresentedasmean±SDoraspercentages(proportions)unlessstatedotherwise.
AnalysiswascarriedoutusingStudent’st-testorone-wayANOVAforcontinuousvariables
andChi-squaredorFisher’sexacttestforcategoricalvariables.Variableswithsignificant
trend(p≤0.1)wereenteredinaCoxproportionalhazardsmodeltoidentifyfactors
independentlyassociatedwithmortalityandstentthrombosis.Differenceinoutcomes
amongpatientsreceivingdifferentP2Y12inhibitorswasevaluatedbyKaplan-Meiersurvival
curvesandlog-ranktest.ClopidogrelandticagrelorwerecomparedforallACSpatientsand
allthreeagentswerecomparedintheSTEMIsubgroup.Allstatisticalanalyseswere
performedusingSPSSversion21(IBMSPSSInc.,NewYork,USA)andRsoftwareversion-
2.13.1(RFoundationforStatisticalComputing,Vienna,Austria).
RESULTS
PatientCharacteristics
Duringthestudyperiod,10,793patientswithACSunderwentcoronaryangiography.The
meanagewas63.6±12.7years;70%ofthepatientsweremalesand15%haddiabetes.
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Abouttwo-thirds(64%)oftheprocedureswereperformedfornon-STelevationacute
coronarysyndrome(NSTE-ACS)andtheremaining(36%)wereforSTEMI.OfallACS
patients,43%(n=4653)receivedclopidogrel,46%(n=4917)receivedticagrelorand11%
(n=1223)receivedprasugrel.Oftheprasugrel-treatedpatients,93%(n=1136)hadSTEMI
andonly7%(n=87)hadNSTE-ACSsoonlytheSTEMIcohortwasincludedintheanalyses.
ACSpatientstreatedwithclopidogrelwereslightlyolderbutlessfrequentlyhadSTEMIor
renalfailurecomparedtothosetreatedwithticagrelor(Table1).Thispartlyreflectedan
increasingprovisionofprimaryPCIforSTEMIduringtheyearsinwhichprasugrelandthen
ticagrelorwereintroducedasoptions.
Ofthe3920(36%)ofpatientswhounderwentcoronaryangiographyforSTEMI,themean
agewas62.9±12.9,73%weremaleand12%haddiabetes.29%(n=1130)received
clopidogrel,29%(n=1136)prasugreland42%(n=1654)ticagrelor.Differenceswerenotedin
someclinicalcharacteristicsbetweenthethreegroups(Table2):prasugrel-treatedpatients
wereyoungerandclopidogrel-treatedpatientsolderthanthosetreatedwithticagrelor;
priorhistoryofstroke/TIAwasmorecommoninclopidogrel-treatedpatients;and
cardiogenicshockwasmorecommoninticagrelor-treatedpatients.
All-causemortalityatoneyear
Ofthe10,793patientswithACS,787(7.3%)diedwithinoneyear.Theuseofticagrelorwas
associatedwithsignificantlylowerall-causemortalityat1-yearcomparedwithclopidogrel
(Figure1A).Theuseofclopidogrelwasanindependentriskfactorformortalityinmultiple
regressionanalysis(Table3).Afteradjustmentfortheindependentriskfactors,therewas
stilllowermortalityinpatientstreatedwithticagrelor(Figure1B).
9
Ofthe3920patientswithSTEMI,340(8.7%)diedwithinoneyear.Theuseofprasugreland
ticagrelor(vsclopidogrel)wasassociatedwithsignificantlylowerall-causemortalityat1-
year(Figure1C).Afteradjustmentforindependentriskfactors,therewasstilllower
mortalityinpatientstreatedwithprasugrelandticagrelorcomparedwithclopidogrel
(Figure1D).
Incidenceofdefinitestentthrombosis
OutofallACSpatients,7595(70%)weretreatedwithPCI.Outofthesepatients,2880(38%)
patientsreceivedclopidogreland3493(46%)ticagrelor.Theremaining1222(16%)received
prasugrel.
AmongPCI-treatedACSpatients,78(1.0%)developeddefinitestentthrombosiswithin12
months.Ofthese,24(31%)wereacute(<24hours),32(41%)subacute(1-30days)and22
(28%)late(31-365days).Halfofthestentthrombosiseventsinpatientstreatedwith
prasugrelorticagrelorwereacutewhereasaboutone-quarteroftheseeventswereacutein
clopidogrel-treatedpatients(Table4).
Theuseofticagrelorwasassociatedwithalowerincidenceofdefinitestentthrombosisat
oneyearcomparedwithclopidogrel(Figure2A).Clopidogrelwasanindependentriskfactor
fordefinitestentthrombosisinmultipleregressionanalysis(Table5).Afteradjustmentfor
independentriskfactors,therewasstilllowerriskofstentthrombosisinticagrelor-treated
patients(Figure2B).
Ofthe3881patientsundergoingPCIforSTEMI,51(1.3%)developedstentthrombosis
within12months.Therewasnosignificantdifferenceintheincidenceofstentthrombosis
betweenclopidogrel-,prasugrel-andticagrelor-treatedpatientsinunadjusted(Figure2C)or
10
adjustedanalysis(Figure2D).
DISCUSSION
Inthis'real-world'registryof10,793patientswithACS,wefoundthatticagrelorwas
associatedwithareductioninmortalitycomparedwithclopidogrelininvasively-managed
ACSpatients,includingafterwehadadjustedfordifferencesinbaselinecharacteristicsthat
wereattributabletoincreasingprovisionofprimaryPCIforSTEMIduringthestudyperiod
andcontraindicationstotheuseofticagrelororprasugrel.Additionally,bothticagrelorand
prasugrelwereassociatedwithareductioninmortalitycomparedtoclopidogrelinthe
STEMIcohort.InallACSpatients,ticagrelorwasalsoassociatedwithlowerratesofstent
thrombosiscomparedtoclopidogrel;however,therewasnosignificantdifferenceinthe
STEMIsubgroup.
DualantiplatelettherapyintheformofaspirinandaP2Y12inhibitordecreasestherisksof
myocardialinfarction,recurrentischaemiaandcardiovasculardeathinabroadspectrumof
ACSpatientsandreducestheriskofstentthrombosisanditssequelaeinPCI-treated
patients[18,19].Theoriginaldualantiplateletregimenconsistedofaspirinplusticlopidine,
whichshowedsuperioritytoaspirinaloneoraspirinpluswarfarin[20,21].Ticlopidinefell
outoffavourduetohaematologicalside-effectsandwasreplacedbythesaferandequally
effectivealternativeofclopidogrel[18,22].However,morecontemporaryconcernsof
resistanceanddrug-druginteractionswithclopidogrelhaveledtothedevelopmentofthe
neweroralP2Y12antagonists,prasugrelandticagrelor[23,24].Prasugrelisapro-drug
metabolizedtoitsactiveformbyCYP3A4andCYP2B6withamorerapidonsetandhigher
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meanlevelofplateletinhibitioncomparedtoclopidogrel.PatientswithACSundergoingPCI
andtreatedwithdualantiplateletincludingprasugrelhadlowerratesofmyocardial
infarction,urgenttarget-vesselrevascularization,andstentthrombosisascomparedtodual
antiplatelettherapywithclopidogrelat15-monthsfollow-upoftheirindexPCIinTRITON-
TIMI-38[10].Thisbenefitwasmostlyrelatedtoareductionintheratesofnon-fatal
myocardialinfarction(7.4%withprasugrelvs9.7%withclopidogrel;HR0.76;95%CI0.67to
0.85;P<0.001)andlowerratesofstentthrombosis(1.1%vs2.4%;P<0.001).Ticagrelorisa
direct-acting,reversibly-bindingagentwithsimilarlyrapidonsetofactioncomparedto
clopidogrelandrequirestwice-dailyadministration.InthePLATOstudy,amongpatients
withACStreatedwithorwithoutaninvasivestrategy,therewasareductioninthe
compositeendpointofdeathfromvascularcauses,myocardialinfarctionorstrokewhen
ticagrelorwasincludedinthedualantiplatelettherapyregimenascomparedtoclopidogrel
(9.8%forticagrelorvs11.7%withclopidogrel;HR0.84;95%CI0.77to0.92;p<0.001)[11].
Ticagreloralsosignificantlyreducedtherateofstentthrombosis[25].Arecentmeta-
analysisoftherandomizedtrialshasalsoshownthebeneficialeffectofnewP2Y12inhibitors
overclopidogrel[26].TheSWEDEHEARTregistryconfirmedthebenefitofticagrelor(vs
clopidogrel)inareal-worldregistryof45,073patientsalbeitwithahigherbleedingrate
[13].Ourdatafromalargeall-comerspopulationhavefurtherconfirmedthebenefitof
ticagrelorinallACSpatientsonbothmortalityandstentthrombosisthatwasseeninthe
clinicaltrialsandrecentregistry.
Bothprasugrelandticagrelorwereassociatedwithreducedmortalitycomparedto
clopidogrelinpatientswithSTEMI,howevertherewasnosignificantdifferencebetweenthe
twoneweragents(Figures1Dand2D).ForpatientswithNSTE-ACS,ticagreloris
12
recommendedinpreferencetoclopidogrelregardlessoftreatmentstrategy[1].Inthe
PLATOtrial,ticagrelorwassuperiortoclopidogrelforpatientswithNSTE-ACSwhether
treatedmedicallyorwithrevascularization[27,28].WhereastheTRITON-TIMItrialshowed
benefitsofprasugrelcomparedtoclopidogrelinpatientswithNSTE-ACStreatedwithPCI,
theTRILOGYACStrialfoundnobenefitwithprasugrelcomparedtoclopidogrelinpatients
withmedically-treatedACS[29].Consequently,prasugrelisonlyrecommendedforNSTE-
ACSmanagedwithPCI.ForpatientswithSTEMImanagedwithprimaryPCI,bothprasugrel
andticagrelorarerecommendedinpreferencetoclopidogrelforpatientswithout
contraindications[3,30].StudiesofplateletreactivityinSTEMIpatientshaveshownsimilar
onsetsofactionofprasugrelandticagrelorloadingdoses,withevidenceofbothbeing
delayedinsomeofthesepatients,atleastpartlyduetomorphinetreatment[31-34].We
foundnosignificantdifferenceinstentthrombosisratesintheSTEMIgroupwiththenewer
P2Y12inhibitors(prasugrelandticagrelor)comparedtoclopidogrel.Furthermore,ahigher
proportionofthestentthrombosisseeninSTEMIoccurredacutely(<24hours)(STEMI45%,
allACS31%).Thismayinpartbeexplainedbytheincreasedadministrationofmorphinein
thesepatients.TheremaypotentiallybearoleofintravenousP2Y12inhibitorsinthese
patients[35,36].
OurresultsarealsoconsistentwiththePRAGUE-18study[14],where1230patients
undergoingprimaryPCIforACSwererandomlyassignedtoprasugrelorticgarelor.There
wasnosignificantdifferenceintheprimaryoutcomecomprisingdeath,re-infarction,urgent
targetvesselrevascularization,stroke,orseriousbleedingobservedat30days.Currently
mostcentresareusingoneorothernewerP2Y12inhibitorforpatientswithSTEMItreated
withprimaryPCI;however,itmaybeappropriatetohavebothdrugsavailableanduseone
13
ortheotherbasedonclinicalprofileofindividualpatientsandrelativecontraindicationsor
sideeffectsofthesedrugs.Prasugrelisgenerallynotrecommendedinolder(>75years)
patientsandiscontraindicatedinthosewithahistoryofstroke,whereasticagrelormaybe
avoidedinpatientswithsinoatrialnodedysfunctionuntreatedwithpermanentpacemaker
orwithintolerabledyspnoearelatedtoticagrelor.
Studylimitations:Thisisanobservationalstudy,withthedataderivedfromaprospectively
compiledregistry.Dataforbleedingcomplications,myocardialinfarctionorstrokewerenot
availableandwereliedonreferralofsurvivorsofstentthrombosisbacktoourPCIcentre
forrecordingofthiscomplication.Inaddition,someaspectsofthedatawereunconfirmed;
forexample,wedidnotevaluatepatients’adherencetotheirantiplatelettreatmentand
ourresultsarebasedonantiplateletprescriptionatindexadmission.Ratesofstent
thrombosisintheSTEMIsubgroupwerelowmakinginterpretationdifficult.Becauseofthe
natureoftheregistry,wedidnotincludeACSpatientswhodidnotundergocoronary
angiographyandsoourresultsonlyprovidedataonACSpatientswhoaremanaged
invasively.
Conclusion:Ticagrelorisassociatedwithimprovedsurvivalandareductioninstent
thrombosiscomparedwithclopidogrelininvasively-managedACSpatients.Bothticagrelor
andprasugrelareassociatedwithreducedmortalityintheSTEMIcohortcomparedwith
clopidogrelbutnosignificantdifferenceinstentthrombosiswasseeninthisgroup.Further
head-to-headcomparisonofprasugrelandticagrelorforSTEMIpatientsiswarrantedinan
adequatelypoweredclinicaltrial.
14
ACKNOWLEDGMENTS
WearegratefultoalltheinterventionalcardiologistsatSouthYorkshireCardiothoracic
Centre.WewouldalsoliketothankLouisaAlcockforhelpwithdataextraction.
DECLARATIONOFINTERESTSTATEMENT
RFStoreyreportsresearchgrants,consultancyfees,andhonorariafromAstraZeneca;
researchgrantsandconsultancyfeesfromPlaqueTec;andconsultancyfeesfromAspen,
Bayer,ThermoFisherScientific,Bristol-MyersSquibb/Pfizeralliance,andTheMedicines
Company.Theotherauthorsreportnoconflictsofinterest.
15
FIGURELEGENDS
Figure1.Cumulativeincidenceofall-causemortalityover1yearshowing(A)unadjusted
ratesinallACSpatientstreatedwitheitherclopidogrelorticagrelor,(B)adjustedratesinall
ACSpatientstreatedwitheitherclopidogrelorticagrelor,(C)unadjustedratesinSTEMI
patientstreatedwithclopidogrel,prasugrelorticagrelor,and(D)adjustedratesinSTEMI
patientstreatedwithclopidogrel,prasugrelorticagrelor.HR:hazardratio;CI:confidence
intervals.
Figure2.Cumulativeincidenceofdefinitestentthrombosisover1yearshowing(A)
unadjustedratesinallACSpatientstreatedwitheitherclopidogrelorticagrelor,(B)
adjustedratesinallACSpatientstreatedwitheitherclopidogrelorticagrelor,(C)
unadjustedratesinSTEMIpatientstreatedwithclopidogrel,prasugrelorticagrelor,and(D)
adjustedratesinSTEMIpatientstreatedwithclopidogrel,prasugrelorticagrelor.HR:hazard
ratio;CI:confidenceintervals.
16
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Table1:ClinicalcharacteristicsofallACSpatientsstratifiedbyantiplatelet.
Characteristic Clopidogrel
N=4653
Ticagrelor
N=4917
P
Age(years) 64.4(+/-12.9) 63.5(+/-12.7) <0.001
Male 3166(68%) 3466(70%) 0.009
STEMI 1130(24%) 1654(34%) <0.001
Renalimpairment 45(1%) 107(2%) <0.001
Diabetesmellitus 687(15%) 798(16%) 0.05
Previousstroke/TIA 143(3%) 144(3%) 0.68
PreviousPCI 320(7%) 359(7%) 0.42
PreviousCABG 149(3%) 141(3%) 0.34
GPIIb/IIIainhibitor 581(12%) 634(13%) 0.55
LMS>50% 340(7.3%) 226(4.6%) <0.001
Hypertension 1882(40%) 2140(44%) 0.002
Dyslipidaemia(treated) 2144(46%) 1903(39%) <0.001
3-vesseldisease 1002(22%) 745(15%) <0.001
PCI 2880(62%) 3353(68%) <0.001
No.ofvesselsattempted 1.2+/-0.48 1.2+/-0.47 0.801
No.ofstentsused 1.59+/-0.92 1.47+/-0.87 <0.001
ReferredforCABG 458(10%) 292(6.2%) <0.001
STEMI:ST-elevationmyocardialinfarction;TIA:transientischaemicattack;PCI:
percutaneouscoronaryintervention;CABG:coronaryarterybypassgraftsurgery;
GP:glycoprotein;LMS:Leftmainstem
21
Table2:ClinicalcharacteristicsofST-elevationmyocardialinfarctionpatientsaccordingto
antiplatelettherapy.
TIA:transientischaemicattack;PCI:percutaneouscoronaryintervention;CABG:coronary
arterybypassgraftsurgery;LMS:Leftmainstem;GP:Glycoprotein
Characteristic Clopidogrel
N=1130
Prasugrel
N=1136
Ticagrelor
N=1654
P
Age(years) 65.2+/-13.7 60.8+/-11.7 62.8+/-12.9 <0.001
Male 804(71%) 870(77%) 1189(72%) 0.005
Renalimpairment 12(1%) 7(1%) 23(1%) 0.144
Diabetesmellitus 141(13%) 121(11%) 216(13%) 0.147
Hypertension 413(37%) 388(34%) 593(36%) 0.477
Dyslipidaemia 444(39%) 419(37%) 470(29%) <0.001
Previousstroke/TIA 57(5%) 32(2.8%) 40(2%) <0.001
PreviousPCI 76(7%) 78(7%) 139(8%) 0.172
PreviousCABG 19(2%) 16(1%) 24(1%) 0.805
Cardiogenicshock 23(2%) 18(2%) 64(4%) <0.001
GPIIb/IIIainhibitors 391(35%) 364(32%) 529(32%) 0.299
LMS>50% 61(5.4%) 31(2.7%) 53(3.2%) 0.001
3-vesseldisease 234(21%) 181(16%) 208(13%) <0.001
PCI 1130(100%) 1135(100%) 1616(98%) <0.001
No.ofvesselsattempted 1.12+/-0.39 1.10+/-0.35 1.09+/-0.39 0.139
No.ofstentsused 1.54+/-0.81 1.50+/-0.82 1.35+/-0.77 <0.001
ReferredforCABG 0(0%) 0(0%) 7(0.4%) <0.001
22
Table3:Independentpredictorsofmortalityinallacutecoronarysyndromepatients
Variable HR 95%CI p
Cardiogenicshock 7.006 5.247-9.353 <0.001
Renalimpairment 3.048 2.199–4.226 <0.001
Emergencyprocedure 2.396 1.959–2.929 <0.001
LMSdisease 1.693 1.350–2.124 <0.001
3-vesseldisease 1.358 1.054-1.750 0.02
Clopidogrel 1.188 1.020-1.382 0.03
Age(years) 1.057 1.050–1.064 <0.001
STEMI 0.805 0.649-0.999 0.05
Dyslipidaemia(treated) 0.796 0.681–0.932 0.004
LMS:leftmainstem;STEMI:ST-elevationmyocardialinfarction
23
Table4:Incidenceandtimingofdefinitestentthrombosisaccordingtoantiplatelettherapy
Clopidogrel Prasugrel Ticagrelor Pvalue
AllPCI-treatedACSpatients,n 2880 - 3353
DefiniteST,n(%) 33(1.1%) - 21(0.6%) 0.02
Acute(%oftotal) 11(33%) - 6(29%)
Sub-acute(%oftotal) 15(45%) - 5(24%)
Late(%oftotal) 7(21%) - 10(48%)
AllPCI-treatedSTEMIpatients,n 1130 1136 1654
DefiniteST,n(%) 17(1.5%) 18(1.6%) 16(1%) 0.29
Acute(%oftotal) 6(26%) 11(61%) 6(38%)
Sub-acute(%oftotal) 7(48%) 5(28%) 4(25%)
Late(%oftotal) 4(26%) 2(11%) 6(38%)
PCI:percutaneouscoronaryintervention;ACS:acutecoronarysyndromes;ST:stent
thrombosis;STEMI:ST-elevationmyocardialinfarction
24
Table5:Independentpredictorsofdefinitestentthrombosiswithin12months
Variable HR 95%CI p
STEMI 2.232 1.286-3.872 0.004
Diabetes 2.191 1.189-4.037 0.01
Clopidogrel 2.057 1.187-3.565 0.01
Age 0.967 0.947-0.987 0.001
STEMI:ST-elevationmyocardialinfarction
25
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