www.revportcardiol.org
Revista
Portuguesa
de
Cardiologia
Portuguese
Journal
of
Cardiology
ORIGINAL
ARTICLE
Adjuvant
antithrombotic
therapy
in
ST-elevation
myocardial
infarction:
Contemporaneous
Portuguese
cross-sectional
data
Daniel
Caldeira
a,b,∗,
Hélder
Pereira
a,
Ana
Marques
a,
Sofia
Alegria
a,
João
Calisto
c,
Pedro
Canas
da
Silva
d,
Vasco
Gama
Ribeiro
e,
João
Carlos
Silva
f,
Filipe
Seixo
g,
Pedro
Farto
e
Abreu
h,
Rui
Campante
Teles
i,
Renato
Fernandes
j,
Henrique
Cyrne
Carvalho
k,
on
behalf
of
investigators
of
the
Portuguese
Registry
of
Acute
Coronary
Syndromes
(ProACS),
investigators
of
the
Portuguese
Registry
on
Interventional
Cardiology
(PRIC)
aCardiologyDepartment,HospitalGarciadeOrta,Almada,Portugal
bLaboratóriodeFarmacologiaClínicaeTerapêutica,CCUL,CAML,FaculdadedeMedicina,UniversidadedeLisboa,Portugal cCentroHospitalareUniversitáriodeCoimbra---HUC,Coimbra,Portugal
dHospitaldeSantaMaria,CentroHospitalardeLisboaNorteEPE,Lisboa,Portugal
eCentroHospitalardeVilaNovadeGaia/Espinho-HospitalEduardoSantosSilva,Porto,Portugal fCentroHospitalardeSãoJoão,Porto,Portugal
gHospitaldeSãoBernardo,CentroHospitalardeSetúbal,Portugal hHospitalProfessorDoutorFernandodaFonseca,Amadora,Portugal
iHospitaldeSantaCruz,CentroHospitalardeLisboaOcidental,Lisboa,Portugal jHospitaldoEspíritoSanto,Évora,Portugal
kHospitaldeSantoAntónio,CentroHospitalardoPorto,Porto,Portugal
Received1January2018;accepted27February2019 Availableonline29January2020
KEYWORDS Myocardialinfarction; Antiplatelet; Anticoagulant; Antithrombotic; Adjuvant Abstract
Introduction:ThestandardofcareforacuteST-elevationmyocardialinfarction(STEMI)includes theactivationofaSTEMIcarenetwork,theadministrationofadjuvantmedicaltherapy,and reperfusion throughprimarypercutaneouscoronaryintervention (PCI).While primaryPCI is nowadaysthefirst optionforthetreatmentofpatients withSTEMI,antithrombotictherapy, includingantiplateletandanticoagulantagents,isthecornerstoneofpharmacological treat-menttooptimizetheirclinicaloutcomes.
Objective: Theaimofthisstudywastodescribecontemporaneousreal-worldpatternsofuse ofantithrombotictreatmentsinPortugalforSTEMIpatientsundergoingprimaryPCI.
∗Correspondingauthor.
E-mailaddress:dgcaldeira@hotmail.com(D.Caldeira).
https://doi.org/10.1016/j.repc.2019.02.015
0870-2551/©2020SociedadePortuguesadeCardiologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Methods:An observational, retrospective cross-sectional study was performed for the year 2016,basedondatafromtwonationalregistries:thePortugueseRegistryonAcuteCoronary Syndromes(ProACS)andthePortugueseRegistryonInterventionalCardiology(PRIC).Dataon oralantiplateletandproceduralintravenousantithromboticdrugswereretrieved.
Results:In2016,theProACSenrolled534STEMIpatientstreatedwithprimaryPCI,whilethe PRICregistryreporteddataon2625STEMIpatients.Ofthese,99.6%weretreatedwithaspirin and75.6% withdual antiplatelet therapy(mostly clopidogrel).GPIIb/IIIa inhibitors(mostly abciximab)wereusedin11.6%ofcases.Heparinswereusedin80%ofcases(78%unfractionated heparin [UFH]and2%low molecularweight heparin). Noneofthepatients includedinthe registryweretreatedwithcangrelor,prasugrelorbivalirudin.Missingdataareoneofthemain limitationsoftheregistries.
Conclusions:In2016,accordingtodatafromthesenationalregistries,almostallpatientswith STEMIwere treatedwith aspirinand76%with dual antiplatelet agents,mostlyclopidogrel. GPIIb/IIIainhibitorswereusedinfewpatients,andUFHwasthemostprevalentparenteral anticoagulantdrug.
©2020SociedadePortuguesadeCardiologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBY-NC-NDlicense (http://creativecommons.org/licenses/by-nc-nd/4.0/). PALAVRAS-CHAVE Enfartedomiocárdio; Antiagregante; Anticoagulante; Antitrombótico; Adjuvante
Terapêuticaantitrombóticaadjuvantenoenfartedomiocárdiocomelevac¸ão dosegmentST:dadosportuguesestransversaiscontemporâneos
Resumo
Introduc¸ão:Otratamentodoenfarteagudodomiocárdiocomelevac¸ãodosegmentST (EAM-CSST)baseia-senaativac¸ãodaviaverdecoronária,naadministrac¸ãodeterapêuticamédica adjuvanteenareperfusãoatravésdeangioplastiaprimáriapercutânea.Aangioplastiaprimária constitui o tratamento de primeira linha para o EAMCSST e a terapêutica antitrombótica, incluindoantiagreganteseanticoagulantes,abasedotratamentofarmacológico,contribuindo paraamelhoriadoprognóstico.
Objetivo:Descreverdadoscontemporâneosdavidarealdautilizac¸ãodeterapêutica antitrom-bóticaemPortugal,emdoentescomEAMCSSTsubmetidosaangioplastiaprimária.
Métodos: Foirealizadoumestudoobservacionalretrospetivobaseadonosdadosdedoisregistos nacionaisreferentesaoanode2016:oRegistoNacionaldeSíndromesCoronáriasAgudas(RNSCA) eoRegistoPortuguêsdeCardiologiadeIntervenc¸ão(RPCI).Foramcolhidosdadosrelativosà utilizac¸ãodeantiagregantes plaquetárioseterapêuticaantitrombóticaendovenosa utilizada naangioplastiaprimária.
Resultados: Duranteoanode2016foramincluídos534doentesnoRNSCAe2625doentesno RNCIcom odiagnóstico de EAMCSSTsubmetidos aangioplastia primária.Aproximadamente 99,6% dosdoentes foramtratadoscom ácido acetilsalicílico(AAS) e75,6% comterapêutica antiagregantedupla(principalmenteclopidogrel).OsinibidoresdorecetordaGpIIbIIIaforam utilizadosem11,6%dasangioplastiasprimárias(principalmenteabxicimab).Relativamenteà terapêuticaanticoagulante,em78%doscasosfoiutilizadaheparinanãofracionada(HNF)eem 2%heparinadebaixopesomolecular.Nenhumdosdoentesincluídonoregistofoitratadocom cangrelor,prasugreloubivalirrudina.Osdadosomissossãoumadasprincipaislimitac¸õesdos registos.
Conclusões:Em2016,deacordocomdadosdosregistosnacionais,quasetodososdoentesforam tratadoscomAASe76%comterapêuticaantiagregantedupla,namaioriadoscasosincluindo oclopidogrel.OsinibidoresdosrecetorsdaGpIIbIIIaforamutilizadosnumnúmeroreduzidode doenteseaHNFfoioprincipalanticoagulanteadministrado.
©2020SociedadePortuguesadeCardiologia.PublicadoporElsevierEspa˜na,S.L.U.Este ´eum artigoOpen Accesssobumalicenc¸aCCBY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
The standard of care for acute ST-elevation myocardial infarction(STEMI)1,2includestheactivationofaSTEMIcare
network, the administrationof adjuvant medicaltherapy, and reperfusion through primary percutaneous coronary intervention(PCI).
Advances in the organizational aspects of health care (suchastheStentForLifeinitiative3,4)andreperfusion
ther-apymeanthatprimaryPCIisnowtheestablishedfirstoption for the treatment of patients with STEMI withimpact on prognosis.
It is clear that the improved results in STEMI care are largelyduetothedevelopmentofadjuvantmedicaltherapy overrecentdecades,inparticularantithrombotictherapy, including antiplatelet and anticoagulant agents, which is nowthecornerstoneofpharmacologicaltreatmentto opti-mizeclinical outcomesin patients withSTEMI undergoing primaryPCI.5
2017 markedthe21stanniversaryof thepublicationof thefirstrandomizedclinicaltrialestablishingthe superior-ityof dualantiplatelettherapy (DAPT) overanticoagulant therapy among patients undergoing PCI.6 The subject of
over 35 randomized clinical trials, including more than 225000patients,DAPTisamongthemostintensively inves-tigated treatment options in the field of cardiovascular medicine.7
DAPTwithaspirinandanoralP2Y12-receptorinhibitoris
pivotal forthe acuteandlong-termtreatment ofpatients withSTEMIundergoingprimaryPCI.Prasugrelandticagrelor provideamoreprompt,potent,andpredictableantiplatelet effectthanclopidogrel,whichtranslatesintobetterclinical outcomes.Therefore,theseagentsarethefirst-line treat-mentinprimaryPCI.However,patientscanstillexperience adverseischemicevents,whichmaybeinpartdueto alter-nativepathwaystriggeringthrombosis.
Intravenous anticoagulant drugs available for primary PCI include the indirect thrombin inhibitors unfraction-ated heparin (UFH) and low molecular weight heparin (LMWH), and the direct thrombin inhibitor bivalirudin. The main intravenous antiplatelet drugs are glycoprotein (GP)IIb/IIIa inhibitors,whichshouldonlybeconsideredin bailouttherapy,intheeventofangiographicevidenceofa large thrombus,slow- or no-reflow, and other thrombotic complications,andtheP2Y12-receptorinhibitorcangrelor.5
Since several new antithrombotic therapies have emerged in recent decades for the treatment of acute coronarysyndromes (ACS),we aimedtodescribe contem-poraneous real-world patterns of use of antithrombotic treatments in Portugal for STEMI patients undergoing pri-mary PCI, through a cross-sectional observational study, basedondatafromnationalregistries.
Methods
An observational, retrospective cross-sectional study was performedfor2016inordertoassessthecontemporaneous useofadjuvantantithrombotictherapyinpatientstreated withprimaryPCIinPortugal.
Data on oral antiplatelet and procedural intravenous antithrombotic drugs were retrieved from two registries:
the Portuguese Registry on Acute Coronary Syndromes (ProACS;ClinicalTrials.govidentifierNCT01642329)andthe PortugueseRegistryonInterventionalCardiology(PRIC; Clin-icalTrials.govidentifierNCT01867801).
The PRIC database is a prospective observational reg-istryofPCIininterventionalcardiologyunitsinPortugalthat includesdatafrom25centers.TheProACSdatabaseisalsoa multicenterprospectiveobservationalregistry,andincludes dataonpatientshospitalizedduetoACSin49centers.
The ProACS registry was used to assess data on oral antithrombotic drugs (prescribed and taken throughout hospital stay) and the PRIC registry was used to assess dataon procedural intravenous antithrombotic treatment (antiplateletandanticoagulantdrugs).
This was a descriptive study and all variables were presented as frequencies and percentages. No inference analysis was performed. The plots were derived from MicrosoftExcel®.
Alldatacollectionfor thePortugueseSociety of Cardi-ology’s National Center for Data Collection in Cardiology (http://www.spc.pt/CNCDC/) and the registryprocedures areinaccordancewiththerulesofthePortugueseNational DataProtectionAuthority.Theregistrywasapprovedbythe PortugueseSociety of Cardiology’sethics committee. This reportwasapprovedbythecoordinatorsofPRICandProACS.
Results
In2016,ProACSenrolled534STEMIpatientstreatedby pri-maryPCI,whilePRICreporteddataon2697STEMIpatients.
Table1showsthecharacteristicsofpatientsenrolledinthe tworegistries.
Almostallpatientsweretreatedwithaspirin(99.6%)and thereportedproportionofpatientstreatedwithDAPTwas 75.6%.Besides aspirin,mostoftheincludedpatientswere stilltreatedwithclopidogrel(54.1%)despitethe evidence-basedefficacy of ticagrelorand prasugrel.Ticagrelor was usedin 36.3%of patients(Figure1).About 15%were pre-scribedbothclopidogrelandticagrelorinthesameepisode. Nopatientsweretreatedwithprasugrelorcangrelor.
About80%reportedtheuseofheparin,78%UFHand2% LMWH(Figure2).Inpatientsnottreatedwithheparin,1% weretreatedwithoralanticoagulantsandonly7%received GPIIb/IIIainhibitors.None ofthepatientsincluded inthe registryweretreatedwithbivalirudin.
GP IIb/IIIa inhibitors were used in 11.6% of cases and abciximab was the most frequently used drug (8.0%) (Figure3).
Discussion
Thiscross-sectionalstudyderivedfromregistrydatashows thatalmostallSTEMIpatientsaretreatedwithantiplatelet agents, and three-quarters with dualantiplatelet agents, mostly clopidogrel. The proportion receiving DAPT would beexpected to behigher (particularly in patients under-goingprimary PCI), and themain antiplatelet agent used wasalsosurprising.ThelowproportionreceivingDAPTmay beduetoincompleteregistrydata.The preponderanceof clopidogrelcanbeexplainedbythelategrantingof reim-bursement(December2013)for ticagrelorinPortugaland
Table1 CharacteristicsofST-elevationmyocardial infarc-tion patients treated by primary percutaneous coronary interventioninthetworegistries.
PRIC ProACS n 2697 534 Age,years 62.9(13.3) 62.3(13.4) Male 75.2% 77.3% Riskfactors Smoking 39.5% 38.0% Diabetes 21.5% 20.5% Hypertension 55.0% 55.8% Dyslipidemia 41.1% 50.0% Comorbidities PreviousMI 11.1% 7.9% Heartfailure 1.2% 1.5% Stroke 4.1% 4.3% PAD 2.1% 3.0%
Chronickidneydisease 3.7% 2.8% Previousinterventions
PreviousPCI 12.9% 7.5%
PreviousCABG 2.1% 0.6%
Timings
Pain-to-balloontime,mina 235(145-440) 252(166-394)
Pain-to-doortime,mina 250(157-458) 164(100-274)
Door-to-balloontime,mina 10(4-22) 54(20-135)
Admission
KillipclassI N/A 89.7% KillipclassII-IV N/A 10.3% LVEF<40% 28.2% 17.7% AdmittedtoaPCIcenter 92.3% 62.9% Transferredfromanon-PCI
center 7.7% 37.1% Culpritvessel LM 1.1% 0.4% LAD 42.6% 46.6% Circumflex 14.8% 11.3% Rightcoronary 37.4% 41.3% CABG 0.5% 0.2% Multivesseldisease 50.9% 39.5% Arterialaccess Radial 79.5% 87.3% Femoral 19.1% 12.7% Brachial 0.4% N/A
PCIwithstent 86.8% 99.8%
DESinatleast1lesion 92.5% 99.6%
Thrombusaspiration 27.1% 23.6%
Completerevascularization 37.7% 73.4%
CABG:coronaryarterybypassgrafting;DES:drug-elutingstent; LAD:leftanteriordescendingartery;LM:leftmain;LVEF:left ventricularejectionfraction;MI:myocardialinfarction;N/A:not available;PAD: peripheralarterial disease,PCI:percutaneous coronary intervention; ProACS: Portuguese Registry of Acute CoronarySyndromes;PRIC:PortugueseRegistryofInterventional Cardiology.
aResultspresentedasmedian(interquartilerange).
itsunavailability in some catheterizationlaboratories and prehospitalemergencytransport.Therewasalso15% conco-mitant useof clopidogreland ticagrelor,whichsuggests a switchinP2Y12inhibitors,movingtoticagrelor(toimprove
theantithromboticeffect)ortoclopidogrel(e.g.needfor DAPTandanticoagulation,inabilitytotolerateticagrelor,or patientpreference).
GP IIb/IIIa inhibitors were used in almost 12% of the patients,presumablyasbailouttherapyorinpatientswith highthromboticburden.5Thechoiceofagentappearedto
berelatedtothegreaterquantityofevidenceavailableon abciximab,eventhoughthisisnotinthecontextof back-groundtreatmentofSTEMI.
UFHwasstillthemostusedanticoagulant,andnocases ofbivalirudinusewererecorded.Accordingtotheregistry data,about20%ofthepatientsdidnotreceiveintravenous anticoagulation,whichmaybeduetoincompletefillingof records(missingdatareached25%)ortocasesinwhich pre-viousadministrationoforalanticoagulantswasnotentered intotherecord.
EarlierdatafromProACSshowedthatintheperiod 2002-2008 the rate of DAPT was 47%, GP IIb/IIIa inhibitor use was20%,andUFHandLMWHwereusedin37%and83%of patients,respectively.8In2010-2011100%ofthe
subpopu-lation withSTEMI andmultivessel diseasein ProACS were prescribedDAPT.9InPRIC,theanalysisof2006-2012showed
useofGPIIb/IIIainhibitorsin31%ofSTEMIpatientstreated byprimaryPCI.10Fortheperiod2006-2012,thePRICshowed
a similar pattern of heparinuse to our contemporaneous analysis,with74%ofSTEMIpatientsusingUFHand3%using LMWH(unpublisheddata).
The rateof DAPT usewas lowerthanexpected, which maybeexplainedbymissingdataorincorrectsubmissionof information.Findingsfromsomeotherregistrieswere bet-terthantheresultsreportedhere.AccordingtothePolish ORPKI nationalregistry, in 2015/2016 therate of DAPT in STEMIpatientswas80%.11TheJapaneseJ-AMIregistry(2011)
revealedthat DAPTwasusedin85% ofSTEMIpatients,6% receivedtripleantiplatelettherapy(addingcilostazol),6% singleantiplatelettherapyand3%noantiplatelettherapy. In Australia(2009-2016),the rateofDAPT in patients dis-charged with ACS was70.4%, but the proportionreached 87%inSTEMIpatients.Infact,STEMIwasapredictorofDAPT prescription.12
IntheItalianEYESHOTregistry,theproportionofpatients receiving GP IIb/IIIa inhibitors, heparins and bivalirudin in the catheterization laboratory was 29%, 66% and 19%, respectively.13
Cross-sectional studies are limited by the methodolo-gies usedin the registries, and in this case the data are collectedonavoluntarybasisandarenotsubjectto exter-nal audit. Inmost centers,data areentered directly into the computersystem during the interventional cardiology procedure,whichresultsinreliabledemographic,clinical, angiographic, and logistic data. However, fewer data are entered onin-hospital course and follow-up, limiting any updateontheuseofdrugs.Therateofmissingdataonat leastonecharacteristic(demographicorriskfactors, medi-calhistory,orin-hospitalmedication)wassignificant,about 25%,andisabiasfactorthatshouldbeacknowledged.This mayexplainwhy24%ofthepatientswerenotreportedtobe
Figure1 Proportionsofpatientsreceivingoralantiplatelettherapyin2016,accordingtotheProACSregistry.
Figure2 Proportionsofpatientsreceivingparenteralanticoagulanttherapyin2016,accordingtothePRICregistry.LMWH:low molecularweightheparin;UFH:unfractionatedheparin.
Figure3 ProportionofpatientsreceivingglycoproteinIIb/IIIainhibitorsin2016,accordingtothePRICregistry.
onDAPT,andwhytherateofPCIperformedwithoutheparin orotherantithromboticdrugswassohigh.
Conclusions
Advances inantithrombotic treatment have ledto signifi-cantimprovementsintheprognosisofpatientswithSTEMI treatedwithprimaryPCI. In2016,accordingtodatafrom these national registries, the majority of STEMI patients
were treated with DAPT, GP IIb/IIIa inhibitors were used in 12% of thesepatients, and in most cases UFH wasthe parenteralanticoagulantdrugofchoiceforSTEMIpatients.
Conflicts
of
interest
References
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