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DUALANTIPLATELETTHERAPY(DAPT)
BHAVISHAH,DNP,APRN,ANP-CUNIVERSITYOFOKLAHOMAHEALTHSCIENCESCENTER
DEPARTMENTOFMEDICINECARDIOLOGYSECTION
WHATREALLYHAPPENS• Normalendotheliumregulatesbloodflow
• TissueInjury– Vasoconstriction– ReleaseofvonWillebrand Factor(vWF)
• Plateletadhesion–– GPIb IX/VandGPIIb/IIIa– vWF bindswithGPIb IX/V
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WHATREALLYHAPPENS…• PlateletActivation
– Degranulation• Releaseof
– FibrinogenandvWF– Serotonin– ADP– activatesotherplatelets– Calcium– Secondaryhemostasis
• ADPreceptors– P2Y1,P2Y12(Important)• FormationofThromboxaneA2(TXA2)usingCyclooxygenase(COX-
1)
• TXA2 promotes• Degranulationofplatelets• Increasesfibrinogenreceptors&• Stimulatesplateletaggregation
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WHATREALLYHAPPENS…
• Plateletaggregation– TXA2andADP
• Activate/expresstheGPIIb/IIIa receptorsontheplatelets
– GPIIb/IIIa bindswithfibrinogen• Bindswithreceptorsonotherplatelets
– PlateletmeshwithGPIIb/IIIa – Fibrinogenbond• GPIIb/IIIa – Fibrinogen– importanttargetforantiplateletmedications
ANTIPLATELETMEDICATIONSCOX-1INHIBITOR
• ASPIRINTHIENOPYRIDINE
• PLAVIX(CLOPIDOGREL)• EFFIENT(PRASUGREL)• TICLOPIDINE(TICLID)
P2Y12RECEPTORBLOCKER• BRILLINTA(TICAGRELOR)
DUALANTIPLATELETMEDICATIONSCOX-1INHIBITOR+ THIENOPYRIDINES/P2Y12
RECEPTORBLOCKER
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ASPIRIN
• IrreversiblyinactivatesCOX-1,whichdecreasesthesynthesisofTXA2andPGI2
• Decreaseinplateletactivation• Analgesic,Anti-inflammatoryandAntipyreticeffect
DOSEAntiplateletmaintenancedose– 81mgAcuteCoronarySyndrome/PCIloading– 160mg–325mg
DURATIONMaintenancedose- Indefinite
ASPIRIN…ADVERSEEFFECTS
COMMONBleedingDyspepsia
N/V/Abd painTinnitusDizziness
ConstipationDiarrhea
SERIOUSBleeding
BronchospasmGIulcers
AnaphylaxisAngioedema
AplasticanemiaAgranulocytosis
DICThrombocytopenia
PancytopeniaNephrotoxicityHepatotoxicity
SalicismReyeSyndrome
ASPIRIN….• Halflife– 15-20min(parentdrug)2-12h(active
metabolite)• Onset– NonEC- 30– 60min• Onset– EC- 3-4hours• PostD/C– 1-4days• Metabolism– GutCYP450system• Excretion– Urine• Pregnancy– Risksnotobservedwithlowdose• Askforanyexistingbleedingdisorders• AskforanyepisodesofGIbleeding,hematuria
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PATIENTEDUCATION
• TakethemedicationwithfoodtoavoidGIsideeffects
• Informhealthcareproviderincaseofshortnessofbreath
• AvoidconcomitantuseofNSAIDswithAspirin
PLAVIX(CLOPIDOGREL)
• Prodrug• IrreversiblybindstoP2Y12ADPreceptor– InhibitsPlateletaggregationinresponsetoADP
DOSELoadingdose- Revascularization– 300mg-600mgMaintenancedose– 75mgPOdaily
DURATIONVariesaccordingtothecardiaceventandtypeofstent
PLAVIX(CLOPIDOGREL)ADVERSEEFFECTS
COMMONBleedingPruritis
SERIOUSBleeding– Hemorrhage
TTPAgranulocytosisPancytopenia
AplasticAnemiaExfoliative dermatitis
Stevens-JohnsonssyndromeErythemamultiforme
ToxicepidermalnecrolysisExanthematous pustulosis
Pneumonia
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PLAVIX(CLOPIDOGREL)…
• Halflife– 8hours• Onset– 24-48hours.MaxEffect– 4-6days• PostD/C– 4-10days• Metabolism– Liver,CYP450(CYP2C19– primary)• Excretion– Urine(50%)Feces(46%)• Pregnancy– BenefitsoutweighRisks• D/Cmedicationatleast5dayspriortoanyelective
surgicalprocedure• Consultprescribingproviderpriortomodificationin
regimen
PATIENTEDUCATION
• Takeuninterruptedataboutthesametimedaily• TakewithfoodtoavoidGIcomplications• Talktoyourproviderpriortoschedulinganyelectivesurgeries/dentalprocedures
• Seekemergencyattentionincaseofunexplained/prolongedbleeding
• AvoidconcomitantuseofOmeprazolewithPlavix
EFFIENT(PRASUGREL)
• Prodrug• IrreversiblebindingtoP2Y12ADPreceptors• Inhibitsplateletactivationandaggregation
DOSELoadingdose– Revascularization- 60mgMaintenancedose– 10mgPOdaily
DURATIONVariesaccordingtothecardiaceventandtypeofstent
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EFFIENT(PRASUGREL)…ADVERSEEFFECTS
COMMONBleeding
Headache/backpain/extremitypain
HTN,hypotensionHLD
ChestpainDyspneaFatigue
AtrialfibrillationBradycardiaFever,rash
PeripheraledemaNausea,diarrhea
Leukopenia
SERIOUSBleeding,Hemorrhage
TTPSeverethrombocytopenia
AnemiaLeukopenia
AtrialfibrillationHepaticimpairment
Hypersensitivityreaction
EFFIENT(PRASUGREL)…• Halflife– 7hours• Metabolism– Liver,CYP450:2B6• Excretion– Urine(68%)Feces(27%)• Pregnancy– BenefitsoutweighRisks• D/Cmedicationatleast7dayspriortoanyelectivesurgical
procedure• Consultprescribingproviderpriortomodificationinregimen• Notrecommendedforpatients>75yrs• Increasedbleedingriskinpatient<60kg• Incaseofbleeding– managewithoutD/Cmedicationduetohigh
riskofcardiovasculareventsespeciallyinfirstfewweeksafterACS
PATIENTEDUCATION
• Takemedicationregularly• Seekemergencyattentionincaseofunexplainedprolongedbleeding.
• Contactproviderbeforestartinganynewmedications
• Talktoyourproviderpriortoschedulinganyelectivesurgeries/dentalprocedures
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BRILLINTA(TICAGRELOR)
• OrallyactiveP2Y12receptorblocker• ReversiblybindstotheP2Y12ADPreceptor– Inhibitsplateletactivationandaggregation
• NotaProdrug– Rapidonsetofaction
DOSELoadingdoseduringrevascularization– 180mgMaintenancedose– 90mgPOBID
DURATIONVariesaccordingtothecardiaceventandtypeofstent
BRILLINTA(TICAGRELOR)ADVERSEEFFECTS
COMMONBleedingDyspnea
CrElevationHeadache
HTN,hypotensionChestpain
Nausea,diarrheaDizziness
AtrialfibrillationFatigueBackpain
SERIOUSBleedingSyncopeAVBlock
Brady-arrhythmiasHypersensitivity
BRILLINTA(TICAGRELOR)• Halflife– 7hours• Metabolism– LiverCYP450:3A4(primary)• Excretion– Urine(26%)Feces(58%)• Pregnancy– BenefitsoutweighRisks• D/Cmedicationatleast5dayspriortoanyelectivesurgical
procedure• Consultprescribingproviderpriortomodificationin
regimen• DonotstartonpatientsundergoingurgentCABG• Contraindicatedincaseofsevereliverdisease• Incaseofbleeding– managewithoutD/Cmedicationdue
tohighriskofcardiovascularevents
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PATIENTEDUCATION
• Takemedicationuninterruptedregularly• Seekemergencyattentionincaseofunexplainedprolongedbleeding.
• Contactproviderbeforestartinganynewmedications
ActionofAntiplatelets andAnticoagulantsinPrimaryHemostasis
• AcuteCoronarySyndrome(ACS)– Clinicalsymptomscompatiblewithacutemyocardialischemiaincluding
unstableangina(UA),Non-ST-segmentelevationmyocardialinfarction(NSTEMI),andSTsegmentelevationmyocardialinfarction(STEMI)
• StableIschemicHeartDisease(SIHD)– PtswithHx ofACS>1yearagowhohaveremainedfreeofrecurrentACSare
saidtohavetransitionedtoSIHD
• PercutaneousCoronaryIntervention(PCI)– Catheterbased,non-surgicalproceduretotreatstenosisofcoronaryarteries
• DrugElutingStents(DES)– Stentswithcontrolledlocalreleaseofanticellproliferativemedication
• BareMetalStents(BMS)– Stentswithoutanydrugcoating
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DAPTGuidelinesforSIHD• SIHDtreatedwithPCI
LevelofEvidence
DES BMS
I ASA(75mg-100mg)POdaily
ASA(75mg-100mg)POdaily
I P2Y12Inhibitor(CLOPIDOGREL)6months
P2Y12Inhibitor(CLOPIDOGREL)1month
IIINo Benefit
Pts withSIHD withoutHx ofACS,PCI,orrecentCABG(within12months)=>DAPTisnotbeneficial
DAPTGuidelinesforACS(NSTEMI/STEMI)• ACStreatedwithPCI
LevelofEvidence
DES BMS
I ASA(75mg-100mg)POdaily
ASA(75mg-100mg)POdaily
I P2Y12Inhibitor(CLOPIDOGREL/TICAGRELOR/PRASUGREL)12months
P2Y12InhibitorCLOPIDOGREL/TICAGRELOR/PRASUGREL)12months
IIIHARM
PRASUGRELshouldNOTbeadministeredinpatients withapriorhistoryofstrokeorTIA
DAPTGuidelinesforACS…
LevelofEvidence
I ACS =>Medicaltherapyw/Fibrinolytics
DAPT(CLOPIDOGREL)minimum for14daysandideally for12months
I ACS =>Medicaltherapyw/oPCIorFibrinolytics
DAPT(TICAGRELOR/CLOPIDOGREL)for12 months
I ASA(75mg-100mg)POdaily
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DAPTguidelinesforCoronaryArteryBypassGraft(CABG)
LevelofEvidence
I PostPCI(onDAPT) =>=>SubsequentCABG
ResumeDAPTpost-optocompleterecommendedduration
I ACS(onDAPT)=>CABG ResumeDAPTpost-optocomplete12months
IASA(75mg-100mg)POdaily
Perioperativemanagement– DAPTforNonCardiac ElectiveSurgery
LevelofEvidence
I NonCardiac Elective surgeries=>Delayfor30daysafterBMSimplantandideally6monthsafterDESimplant
I If unabletopostponesurgery=>ContinueASA81mgperioperatively andresumeP1Y12inhibitorassoonaspossible
IIIHARM
ElectiveNonCardiac surgery shouldNOTbeperformedwithin30daysofBMSimplantandwithin3monthsofDESimplant
MEDICATIONCOMPLIANCE
• ImportanceofDAPTincaseofcoronaryarteryrevascularization– Adherenceiscritical– Stentthrombosis/Instentrestenosis– AcuteCoronarySyndrome– BMSvsDES
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PREVENTION
• LifestyleModification– PhysicalActivity
• Riskfactormanagement– Diabetesmanagement– Hypertensionmanagement– Smokingcessation– Dietarymodification
• Follow-upcompliance• Medicationcompliance
DAPT
Questions??
References• Kumar,A.,&Cannon,C.P.(2009).Acutecoronarysyndromes:Diagnosisandmanagement,PartI.,
MayoClinicProceedings, 84(10),917-938• Buchanan,G.,Basavarajaiah,S.,&Chieffo,A.(2012).Stentthrombosis:Incidence,predictors,and
newtechnologies.Thrombosis.DOI:http://dx.doi.org/10.1155/2012/956962• Airoldi,A.,Colombo,N.,Morici.,etal.(2007).Incidenceandpredictorsofdrug-elutingstent
thrombosisduringandafterdiscontinuationoftheinophylline treatment.Circulation,16(7),745-754
• Stefanini,G.,&Holmes,D.(2013).Drug-elutingcoronaryarterystents.NewEnglandJournalofMedicine.368,254-265.DOI:10.1056/NEJMra1210816
• Maisel,W.,&Laskey,W.(2007).Drug-elutingstents.Circulation.115,426-427.https://doi.org/10.1161/CIRCULATIONAHA.107.688176
• Levine,G.,Bates,E.,Bittl,J.Brindis,R.,Fihn,S.,Fleisher,L.,……&Smith,S.(2016).2016ACC/AHAguidelinesfocusedupdateondurationofdualantiplatelettherapyinpatientswithcoronaryarterydisease.JournalofAmericanCollegeofCardiology. 68(10).DOI:10.1016/j.jacc.2016.03.513
• Sofi,M.(N.D.).Bleeding&clottingdisorders.Retrievedfromhttp://slideplayer.com/slide/8856458/• Bhatt,D.,Hulot,J.,Moliterno,D.,&Harrington,R.(2014).Antiplateletandanticoagulationtherapy
foracutecoronarysyndromes.CirculationResearch.114(12).DOI:https://doi.org/10.1161/CIRCRESAHA.114.302737
• Meek,I.,Vonkeman,H.,Kasemier,J.,Movig,K.,vandeLaar,M.(2012).InterferenceofNSAIDswiththethrombocyteinhibitoryeffectofaspirin:Aplacebo-controlled,exvivo,serialplacebo-controlledserialcrossoverstudy.EuropeanJournalofClinicalPharmacy,69(3),365-371