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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??

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• Sofi,M.(N.D.).Bleeding&clottingdisorders.Retrievedfromhttp://slideplayer.com/slide/8856458/• Bhatt,D.,Hulot,J.,Moliterno,D.,&Harrington,R.(2014).Antiplateletandanticoagulationtherapy

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