The DOACs - How and in Whom Scott C. Woller, MD · PDF fileThe DOACs - How and in Whom Scott C. Woller, MD Medical Director, Anticoagulation Management, Intermountain Healthcare Cenral

TheDOACs-HowandinWhom

ScottC.Woller,MDMedicalDirector,AnticoagulationManagement,IntermountainHealthcareCenralRegion,Co-DirectorVenousThromboemolism

Program,IntermountainMedicalCenter;AssociateProfessor,InternalMedicine,UniversityofUtahSchoolofMedicine;SaltLakeCity,Utah

Objectives:• DiscussandoutlineastrategytoselectamongtheavailableDOAC

medicationsforpatientswithVTEandvariouscharacteristicsandcomorbidities.

• IndicatetheavailablereversalagentsforDOACsandreviewmanagementstrategiestoaddressbleedinginpatientstakingDOACs.

• DescribelimitationstotheunderstandingofDOACinterruption,anddescribeastandardizedapproachtoperi-proceduralinterruptionofDOACs.

Directoralanticoagulants:HowtouseDOACsandinwhom?

ScottC.Woller,MDCo-DirectorThrombosisProgram,IntermountainMedicalCenterAssociateProfessorofClinicalMedicine,UniversityofUtahSchoolofMedicine

ThrombosisGuidelinesSymposiumIntermountainMedicalCenterApril22,2016

Disclosures

PanelistfortheAmericanCollegeofChestPhysicians10theditionGuidelineforAntithromboticTherapyforVTEDisease

PanelistfortheAnticoagulationForumClinicalGuidanceManagementofvenousthromboembolisminitiative

Ihavebeenawardedgrantfundingpaidtomyemployer(IntermountainHealthcare)fromBristol-MeyersSquibb

LearningObjectives• Attheconclusionofthisactivity,participantsshouldbeableto:

• OutlineastrategytoselectamongtheavailableDOACmedicationsforpatientswithVTEandvariouscharacteristicsandcomorbidities.

• IndicatetheavailablereversalagentsforDOACSandreviewmanagementstrategiestoaddressbleedinginpatientstakingDOACs.

• DescribelimitationstotheunderstandingofDOACinterruption,anddescribeastandardizedapproachtotheirperi-proceduralinterruption.

Naminganewclassofmedicines

NOAC: Non Vitamin K Oral AnticoagulantISTHGuidanceStatementJThromb Haemost.2015Jun;13(6):1154-6

TheDirectOralAnticoagulants(DOACs)

http://theuniquesheep.blogspot.com/; http://merchandise.thedoctorwhosite.co.uk/doctor-who-masterpiece-collection-gold-dalek/

TF

Va

VIIa

sciencecodex.com

DOACs

“Acutetherapy”representstheinitialphasewhichoftenincludesahigherdoseorparenteraldrug.

TheminimumdurationofanticoagulanttherapyforDVTorPEisusuallythreemonths,andthisperiodoftreatmentisreferredtoas"long-termtherapy".

Adecisiontotreatpatientsforlongerthan3monthsisreferredtoas"extendedtherapy”.

KearonC.Chest. 2016.doi:10.1016/j.chest.2015.11.026

Nomenclatureofvenousthromboembolismtherapy

TheDirectOralAnticoagulantsRivaroxaban Apixaban Edoxaban Dabigatran

BRANDNAMEPHARMACEUTICAL

Xarleto™

BayerEliquis™

BMS&PfizerSavaysa™

DaiichiSankyoPradaxa™

Boehringer Ingelheim

TARGET FactorXa FactorXa FactorXa FactorIIa

BIOAVAILABILITY(%) ~80 ~50 62 6–7

TIMETOPEAK(h) 2–3 1–2 1-2 1.5

HALF-LIFE(h) 9-13 8-15 9-10 12-14

RENALEXCRETION(%) 33 25 35 >80

EFFECTONaPTT/PT* 1.8/2.6 1.2/~2 yes 2.3/NR

EFFECTONXa 68% NR NR NoEffect

DRUGINTERACTIONS CYP3A4IND/INH CYP3A4INH P-gp INH/CYP3A4 Verapamil/rifampin

Derived from: Crowther. Blood. 2008;111:4871-4879; Garcia, D. Blood. 2010;115:15-20; http://www.eliquis.com/PDF/ELIQUIS%20%C2%AE%20(apixaban)%20SmPC.pdf Schulman ThrombHaemost 2014;111:

MetabolismofDOACs

Nutescu JThromb Thrombolysis(2016)41:15–31Heidbuchel 2013

DRUG RIVAROXABAN APIXABAN EDOXABAN DABIGATRAN

TRIAL EINSTEIN-PE+DVT AMPLIFY HOKUSAI RE-COVERDose 15mg BIDx21d;

20mgQD10mgBDXx7d;

5mgBIDLMMH then60mgQD(30mgCrCl30-50;<60kg)

LMWHthen150mg BIDx6mo.

Comparator/TTR% LWWH+Warf/61% LWWH+Warf/61% LMWH+Warf/63.5% LWWH+Warf/60%

Condition (%) PE61%DVT64% DVT65PE25B10 DVT60PE40B24 DVT70PE20 B10

Enrolled 8281 5395 8240 2539

Design ROL NI RDBNI R DBNI RDBNI

Age/ %♂ 57yrs/55% 57 /61% 55.8 /57% 55yrs/58%

Cancer 5% 2.5% 9.2% 5%

1o Efficacy RecurrentVTE Recur. VTE+VTE death Recur. VTE+VTE death Recur.VTE+death

PrimarySafety MB +CRNMB MB+CRNMB MB+CRNMB Bleeding/ACS/LFT

EfficacyOutcome 2.3v.2.1; RR0.9(0.68-1.2)p<0.003NI

2.3vs.2.7RR0.84(0.6-1.2)p<0.001NI

3.2vs.3.5RR0.89(0.7-1.1)p<0.001NI

2.4v.2.1; RR1.1(0.65-1.84)

MajorBleeding 1.7v.2.2RR0.55(0.38-0.51)p=<0.05sup

0.6vs.1.8 RR0.31(0.17-0.55) p<0.001sup

1.4vs.1.6RR0.84(0.59-1.21)p=0.35sup

1.6v.1.9 RR0.82(ns)

Anybleeding 10.3vs. 11.4% CRB: 4.3 vs.9.7% 21.7%vs.25.6% HR 0.71(0.59-0.85)

Summary Non-inferior;QDdose Non-inferior andsafer Non-inferior,QD Non-inferior

SchulmanNEJM2009;361:2342; EINSTEINInvestigatorsNEJMDec4,2010;AMPLIFYNEJM1Jul2013;HOKUSAINEJM1Sept 2013

DOACsforVTE:TheLong-termTreatmentClinicalTrials

RESOURCESFORAT10GUIDELINESTATEMENT• Dabigatranforlong-termtreatmentofVTE

• RE-COVERNEngl JMed.2009Dec10;361(24):2342-52.• RE-MEDY/RE-SONATENEngl JMed.2013Feb21;368(8):709-18• RE-COVERIITrialInvestigators.Circulation.2014Feb18;129(7):764-72

• Rivaroxabanforacuteandlong-termtreatmentofVTE• PrinsMH,etal.Thromb J.2013Sep20;11(1):21• EINSTEINInvestigators.NEngl JMed.2010Dec23;363(26):2499-510• EINSTEIN–PEInvestigators.NEngl JMed.2012Apr5;366(14):1287-97

• ApixabanforacuteandlongtermtreatmentofVTE• AMPLIFYInvestigators.NEngl JMed.2013Aug29;369(9):799-808.

• Edoxabanforlong-termtreatmentofVTE• Hokusai-VTEInvestigators.NEngl JMed.2013Oct10;369(15):1406-15.


AT10:Choiceofanticoagulantforlong-termtreatmentofDVTandPE:DOACvs.warfarin

AT10Summaryofevidence:RecurrentVTEQUESTION:ShouldaDOACorwarfarinbeusedforacuteandlong-termtreatmentofVTE?

Qualityassessment SummaryofFindingsNOACn(studies)

Riskofbias Overallqualityofevidence

Studyeventrates(%) Relativeeffect(95% CI)

AnticipatedabsoluteeffectsWithLMWHand

VKAWithNOAC Riskw/LMWH

&VKARiskdifferencewith

NOACs(95%CI)

RecurrentVTERIVAROXABAN 8281(2studies)

noseriousriskofbias

⊕⊕⊕⊝MODERATE

duetoimprecision

95/4131 (2.3%)

86/4150 (2.1%)

RR 0.90 (0.68 to 1.2)

23 per 1000 2 fewer per 1000(from 7 fewer

to 5 more)

DABIGATRAN 5107(2studies)

noseriousriskofbias


duetoimprecision

55/2554 (2.2%)2

60/2553 (2.4%)

RR 1.12 (0.77 to 1.62)

22 per 1000 3 more per 1000(from 5 fewer to 13 more)

APIXABAN5244(1study)

noseriousriskofbias


duetoimprecision

71/2635 (2.7%)

59/2609 (2.3%)

RR 0.84 (0.6 to 1.18)


to 5 more)

EDOXABAN8240(1study)

noseriousriskofbias


duetoimprecision

146/4122 (3.5%)3

130/4118 (3.2%)

RR 0.83 (0.57 to 1.21)


to 7 more)

AT10Summaryofevidence:MajorBleedingQUESTION:ShouldaDOACorwarfarinbeusedforacuteandlong-termtreatmentofVTE?

Qualityassessment SummaryofFindingsNOACn(studies)

Riskofbias Overallqualityofevidence

Studyeventrates(%) Relativeeffect(95% CI)

AnticipatedabsoluteeffectsWithLMWHand

VKAWithNOAC Riskwith

LMWHandVKARiskdifferencewith

NOACs(95% CI)

MajorBleedingRIVAROXABAN8246(2studies)

noseriousriskofbias

⊕⊕⊕⊕HIGH

72/4116 (1.7%)4

40/4130 (0.97%)

RR 0.55 (0.38 to 0.81)

17 per 1000 8 fewer per 1000(from 3 fewer to 11

fewer)

DABIGATRAN5107(2studies)

noseriousriskofbias


duetoimprecision

51/2554 (2%)2

37/2553 (1.4%)

RR 0.73 (0.48 to 1.1)


more)

APIXABAN5365(1study)

noseriousriskofbias

⊕⊕⊕⊕HIGH

49/2689 (1.8%)

15/2676 (0.56%)

RR 0.31 (0.17 to 0.55)


fewer)

EDOXABAN8240(1study)

noseriousriskofbias


duetoimprecision

66/4122 (1.6%)

56/4118 (1.4%)

RR 0.85 (0.6 to 1.21)


more)

EvaluationofIndividualswithPulmonaryNodules:GeneralApproachDespitethelackofanantidotefortheDOACs,theriskthatamajorbleedwillbefatalappearstobenohigherthanthatforwarfarin

Theriskofbleeding(particularlyintracranialbleeding)withtheNOACsislessthanwithVKAtherapy

Costandcoveragewillrepresentanimportant“real-world”patientimportantfactorinchoosinglong-termanticoagulant

AT10Choiceofanticoagulantforlong-termtreatmentofDVTandPE:DOACvs.warfarin

EvaluationofIndividualswithPulmonaryNodules:GeneralApproachRecommendedtherapyforVTEtakesintoconsiderationefficacy,safety,andburdenoftreatment.Thisalsocanincludecost.

Isthereevidencetorecommend1DOACoveranother?DOACshavenotbeencomparedhead-to-headforpatient-importantoutcomes.BasedonindirectcomparisonstheseoutcomesappeartobesimilarwithalloftheNOACs

Individualpatientcharacteristics(includingcostandinsurancecoverage)willlikelydrivechoiceofanticoagulantfortheinitial3monthsoftherapy


EvaluationofIndividualswithPulmonaryNodules:GeneralApproachAT10GuidelineStatement:


InpatientswithDVTofthelegorPEandnocancer,aslong-term(first3months)anticoagulanttherapy,wesuggestapixabanoredoxabanorrivaroxabanordabigatranoverVKAtherapy (Grade2B).Remarks:Acutetherapywithparenteralanticoagulationisgivenbeforedabigatranandedoxaban.


Forthefirsttimeanalternativetousualcarewithlowmolecularweightheparinandwarfarinhasbeensuggestedforthelong-termtreatmentofPEandDVT.

Fromtheclinicaltrials:

• Needforthrombolytictherapy• AnindicationforanticoagulationforwhichDOACapprovaldoesnotexist• Highriskofbleeding• Significantliverdisease(acuteorchronichepatitis,cirrhosis,orAST/ALT≥3xULN)• Creatinineclearance30mL/min(forapixabanthethresholdwas25mL/min)• Aspirinuse(100mg/day)• Concomitantuseofinteractingmedications• Uncontrolledhypertension

Whoisnot?

WhoisacandidateforaDOACtherapytotreatVTE?

SchulmanS(2013)NEnglJMed368:709–718.EINSTEINInvestigators(2010)NEnglJMed363:2499–2510.AgnelliG(2013)NEngl JMed368:699–708. SchulmanS(2009)NEnglJMed361:2342–2352.SchulmanS(2014)Circulation129:764–772EINSTEIN–PEInvestigators(2012).NEnglJMed366:1287–1297. AgnelliG(2013)NEngl JMed369:799–808.Hokusai-VTEInvestigators(2013)NEnglJMed369:1406–1415.

Fromtheschoolofhardknocks:

• Patientswhostrugglewithcompliance(unlessrelatedtotransportationforINRs)• Warfarinislikelyfavorabletoallowascertainmentofandanticoagulanteffect

• Financialbarrierstolongitudinalcompliance• After1.1yearf/u<50%prescribedDOACpickedupadequatedrugtocover80%days

Whoisnot?

WhoisacandidateforaDOACtherapytotreatVTE?

KearonCAT10Chest2016;Yao,XChestPhysicianVol.11,No.2Feb.2016

CandidatesforaDOACtherapy:Specialpopulations

Pregnancy


XARELTO-PM-ENG-10JUL2014-172618.pdf.http://www.bayerBoehringer Ingelheim CanadaLtd(2014)Pradaxa productmonograph.http://www.boehringeringelheim.ca;imagesfrom:colorbox.com;dailykos.com

+Dabigatranorrivaroxaban=

• Apixabanhasnohumandatainpregnancy,butshowednomaternalorfetalharminanimalstudies

• Edoxabananimalstudiesdemonstratednofetalharm

• DOACexcretioninbreastmilkisnotknown.

Pregnancy


dailykos.com

Extremesofweight


• Evidenceislimited• Patients<50–60kgwere2–13%ofDOACstudypopulations&

16%ofpatientswere>100kg• 1meta-analysisshowedthatforpatients>100kgrecurrentVTE

riskwas0.9(95%CI0.77-1.06)• Dabigatrandoesnotappeartobeaffectedbyextremesofweight• Weightmayaffectkineticsofanti-Xa’s buttheclinicalsignificance

isunknown. SchulmanNEJM2009;EINSTEINInvestigatorsNEJM2010;AMPLIFYNEJM 2013;HOKUSAINEJM2013;Stangier DJClin Pharmacokinet 2008;FrostJ.thromb Haemost 2009;Upreti VV2013BrJClin Pharmacol;Kubitza D2007 JClin Pharmacol;clipartbest.com;vanEs Blood.2014

Extremesofweight


dailykos.com

Elderly


• Evidencefromameta-analysisofthePhase3trialsstudyingVTE

• PooledDOACvs.VKAforage≥75yearsforrecurrentVTEorVTE-relateddeath:HR0.56(95%CI0.38-0.82)p=0.003

• PooledDOACvs.VKAforage≥75yearsforMajorbleeding:HR0.49(95%CI0.25-0.96)p=0.04

vanEs N.Blood.2014;pintrest.com

Elderly


vanEs N.Blood.2014;pintrest.com

Thrombophilias


• Evidenceislimited• Patientswiththrombophilias comprised2-18%ofthoseenrolled

inDOACtrials

• Post-hocdabigatrandatashowsnodifferenceinrecurrentVTE

• Exception:APS--3ongoingstudies• RAPS(Canada),TRAPS(Italy),ASTRO-APS(USA)

SchulmanS(2013)NEnglJMed368:709–718.EINSTEINInvestigators(2010)NEnglJMed363:2499–2510.AgnelliG(2013)NEngl JMed368:699–708. SchulmanS(2009)NEnglJMed361:2342–2352.SchulmanS(2014)Circulation129:764–772EINSTEIN–PEInvestigators(2012).NEnglJMed366:1287–1297. AgnelliG(2013)NEngl JMed369:799–808.Hokusai-VTEInvestigators(2013)NEnglJMed369:1406–1415;SchulmanSetal(2014)ASH56thannualmeetingDec 2014,session332abstract1544

Thrombophilias


Thrombophilias


APS=

Cancer


• NodedicatedRCTevidenceforcancerpatientsexists• Systematicreviewsofthecancersubgroupfromtheclinical

trialssuggestDOACsaresimilartoVKAforVTErecurrenceriskreductionandnodifferenceinMB/CRNMB

• 1meta-analysissuggestedforVTErecurrenceRR0.57(95%CI0.36-0.91;p=0.02)

SchulmanS2013NEJMEINSTEINInvestigators2010NEJM;AgnelliG2013NEJM;SchulmanS2009NEJM;SchulmanS2014Circulation;EINSTEIN–PEInvestigators2012 NEJM;AgnelliG2013NEJM;Hokusai-VTEInvestigators2013NEJM;CastellucciLA.2014JAMA;CarrierM.2014Thromb Res;VedovatiMC.2015Chest;DiMinno MN.2014JThromb Haemost;FranchiniM.2015Thromb Res

Cancer


SchulmanS2013NEJMEINSTEINInvestigators2010NEJM;AgnelliG2013NEJM;SchulmanS2009NEJM;SchulmanS2014Circulation;EINSTEIN–PEInvestigators2012 NEJM;AgnelliG2013NEJM;Hokusai-VTEInvestigators2013NEJM;CastellucciLA.2014JAMA;CarrierM.2014Thromb Res;VedovatiMC.2015Chest;DiMinno MN.2014JThromb Haemost;FranchiniM.2015Thromb Res;va Es 2015;KearonCAT102016

• AT10statesthat“ForVTEandcancer,wesuggestLMWHoverVKA(Grade2B),dabigatran(Grade2C),rivaroxaban(Grade2C),apixaban(Grade2C),oredoxaban(Grade2C).”

• NocomparisonofDOACwithLMWHtodate• 5ongoingtrials(rivaroxaban=2,apixaban=2,edoxaban=1)

clinicaltrials.govaccessed12MAR2016

Cancer


KearonCAT102016

Cancer


ChoosingbetweenDOACsforVTE:Summary

Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban

Cost +++ + + + +

Compliance +++ + ++ + ++

Bleeding risk + ++ ++(+)* +++ ++

Renal Dysfunction

+++ + + ++ +

QOL + ++ +++ ++ +++*perhapsanincreasedGIBsignal

MonitoringofDOACs

youtube.com

MonitoringofDOACsDOACmonitoringisnotroutinelyrecommended

DetectclinicallyrelevantlevelsofDOACs• Urgentoremergentinvasiveprocedure• Hemorrhage• Neuraxial anesthesia• Majortrauma• Potentialthrombolysisinacutethromboembolism

Derived from:BurnettAEJThromb Thrombolysis(2016)41:206–232


Detectexpectedon-therapylevelsofDOACs• Eventontherapy• Questionssurroundingadherence



DetectofexcessivelevelsofDOACs• Hemorrhage• Overdose• Hepatic/renalimpairment• Druginteractions



MostcircumstancesthatwouldtriggeradesiretomonitoreffectareurgentMajorBleeding:• Supportivecare• Administrationofbloodproducts• Asapplicable,administrationofantidote


Dabigatran: ClottingAssaySummary

DabigatranConcentration

Clottin

gTime(sec)

PT/INR

aPTT

TTECT

Expectedmediantherapeuticdrugconcentrations

Expected95th percentiletherapeuticdrugconcentrations

SlidecourtesyofR.Pendleton

EvaluationofanticoagulanteffectofDabigatran

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

100 200 300 400 500 600 700 800 900

DabigatraneffectonaPTT

aPTT

ratio

DabigatranConcentration(ng/mL)Derived fromvanRynThromb Haemost 2010;103:1116

MonitoringofDOACs:SummaryDOACmonitoringisnotroutinelyrecommended

ItmaybeoccasionallyhelpfultoascertainaqualitativeaffectofDOACsPTT(dabigatran)PT(rivaroxaban,?apixaban)

Quantitativemeasurementmaybecomemorewidelyavailable• dTT,ECT(dabigatran)DOACanti-Xa (apixaban,rivaroxaban,edoxaban)• LMWHanti-Xa (apixaban,rivaroxaban,edoxaban)

Theclinicalvalueofmonitoringmaybeuncertain


MonitoringofDOACs:SummaryAssess for on-therapy

(quantitative)Interpretation Assess for on-therapy

(qualitative)Qualitative

assessment for drug

dabigatran dTT,ECT NLTTexcludes

PTT NL maybeunreliable

rivaroxaban Anti-Xa* NLanti-Xaexcludes

PT NLlikelyexcludes

apixaban Anti-Xa* NLanti-Xaexcludes

-- --

edoxaban Anti-Xa* NLanti-Xaexcludes

-- --

*Standardchromogenicanti-Xa calibratedtoUFHorLMWHmaybeused asaqualitativealternative DerivedfromBurnettJThromb Thrombolysis (2016)41:206

ReversalofDOACeffectIstherearoleforreversalagentsfortheDOACs?

• Shortt1/2

• ClinicaltrialsdemonstratethatregardlessoftheabsenceofanantidoteclinicallyimportantbleedingappearsnomorefrequentlyandmayoccurlesswithDOACscomparedwithVKA

BurnettAEJThromb Thrombolysis(2016)41:206–232;WuCThromb Res.2015;Castellucci LA, JAMA2014;Chai-Adisaksopha C.Blood2014


EvidenceagainsttheroutineneedforDOACmonitoring• AT10summaryofbleedingrisk

• Real-worldexperienceDresdenregistryof1776patientsfollowed1.1years• 1082bleedingeventsoccurringin762patientswereevaluated• 3.4%experiencedmajorbleeding(ISTHcriteria)

• 62%treatedconservatively• 38%requiredsurgeryoranintervention

• FFPorPCCgivenin6patients(norFVII given)• 1deathataweek

• Conclusion:Inreallife,ratesofrivaroxaban-relatedMBmaybelower&atleastnotworsethanVKA

Beyer-Westendorf J.Blood.2014;124(6):955-962)


• InVTEpatients:• Theper-100patientyearincidencerateofmajorbleedingofDOACvs.VKA:0.35(95%CI,0.17-0.68,p=0.0023).

• INallDOACs:

WuCThromb Res.2015;Castellucci LA, JAMA2014;Chai-Adisaksopha C.Blood2014


• INallDOACs:



• INallDOACs:


ReversalofDOACs

ReversalofDOACs:Idarucizumab

NEngl JMed2015;373:511-20.

� “Idarucizumab completelyreversedtheanticoagulanteffectofdabigatranwithinminutes”

� FDAApprovedOctober16,2015

Andexanet alpha

https://www.youtube.com/watch?v=LFf1WRGNZhg/ FromNEJM.org

RecombinantcompetitiveinhibitorofFactorXa

Andexanet AlfafortheReversalofXa Inhibitors

-94

100

-21

11

-92

96

-18

7

anti-Xaactivity Thrombinrestoration

RESULTS

apixaban placebo rivaroxaban placebo2

Siegal DMNEJM2015;373:2413

%

ReversalofDOACs:Aripazine (PER977)

http://cardiac-safety.org/wp-content/uploads/2014/11/3.-James-Costin_Perosphere.pdf accessed18Nov2015

Smallwatersolublemoleculethatnon-covalentlybendsthebindingsiteofallanticoagulants

ReversalofDOACs:Aripazine (PER977)

http://cardiac-safety.org/wp-content/uploads/2014/11/3.-James-Costin_Perosphere.pdf accessed18Nov2015

Perioperativeinterruption:TheDOACs

• About2.5MAmericansrequirelong-termanticoagulation

• About10%requireinterruptionannually

• Generally,interrupt4-5half-livesbeforeHBRprocedure

• OKtointerrupt2-3half-livesbeforeLBRprocedure

• Half-lifeincreasesascreatinineclearancedeclinesAndersonMClev.Clin JMed,2014, 8;629;

InterruptionofDOACsHow many doses do I hold before a procedure?

Rivaroxaban Apixaban Edoxaban DabigatranProcedure:interruption:

Low Bleed Risk2-3 t1/2

High Bleed risk4-5 t1/2







CrCl> 80

1 2 2 4 1 2 2 5-6CrCl50-79

1 2 2 4 1 2 3-4 6-7CrCl30-49

1 2 3-4 6-7 1 2 4-5 7-8CrCl15-29

1-2 2-3 3-4 6-7 2 3-4 5-7 9-12

DerivedfromBurnettJThromb Thrombolysis (2016)41:206











CrCl> 80

1 2 2 4 1 2 2 5-6CrCl50-79

1 2 2 4 1 2 3-4 6-7CrCl30-49

1 2 3-4 6-7 1 2 4-5 7-8CrCl15-29

1-2 2-3 3-4 6-7 2 3-4 5-7 9-12












CrCl> 80

1 2 2 4 1 2 2 5-6CrCl50-79

1 2 2 4 1 2 3-4 6-7CrCl30-49

1 2 3-4 6-7 1 2 4-5 7-8CrCl15-29

1-2 2-3 3-4 6-7 2 3-4 5-7 9-12












CrCl> 80

1 2 2 4 1 2 2 5-6CrCl50-79

1 2 2 4 1 2 3-4 6-7CrCl30-49

1 2 3-4 6-7 1 2 4-5 7-8CrCl15-29

1-2 2-3 3-4 6-7 2 3-4 5-7 9-12


Follow-upforpatientsonaDOAC

• Follow-upvisitsshouldfocuson3objectives:• EnsuringproperDOAC• Maximizingadherence• Minimizingbleeding.

• A(adherence)• B(bleeding)• C(creatinineclearance)• D(druginteractions)• E(examination)• F(follow-up)

GladstoneDJAnnInternMed.2015;163:382-385.

Follow-upforpatientsonaDOAC

http://thrombosiscanada.ca

GladstoneDJAnnInternMed.2015;163:382-385.

SummaryDOACsareeffectiveandsafeforthelong-termtreatmentofVTE

Forthe1st timeamajorguidelinerecommendsatreatmentotherthanVKAforVTEPatientsshouldbeconsideredonacasebycasebasisforthe1st lineuseofDOACs

BewareofDOACuseamongspecialpopulations

RoutinemonitoringofDOACsisnotrecommended

ReversalagentsfortheDOACsarehere(withmoretocome)

Anticoagulantsaredangerousdrugsthatrequirethoughtfuluseandfollow-up

The DOACs - How and in Whom Scott C. Woller, MD · PDF fileThe DOACs - How and in Whom Scott C. Woller, MD Medical Director, Anticoagulation Management, Intermountain Healthcare Cenral

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