ACCP-10-靜脈血栓栓塞癥抗血栓治療Antithrombotic Therapy for VTE Disease-CHEST Guideline-20161

AcceptedManuscript

AntithromboticTherapyforVTEDisease:CHESTGuideline

CliveKearon,MD,PhD,ElieA.Akl,MD,MPH,PhD,JosephOrnelas,PhD,AllenBlaivas,DO,FCCP,DavidJimenez,MD,PhD,FCCP,HenriBounameaux,MD,MennoHuisman,MD,PhD,ChristopherS.King,MD,FCCP,TimothyMorris,MD,FCCP,NamitaSood,MD,FCCP,ScottM.Stevens,MD,JanineR.E.Vintch,MD,FCCP,PhilipWells,MD,ScottC.Woller,MD,Col.LisaMoores,MD,FCCP

PII: S0012-3692(15)00335-9

DOI:

10.1016/j.chest.2015.11.026

Reference: CHEST203Toappearin: CHEST

ReceivedDate:18June2015

RevisedDate: 24November2015

AcceptedDate:25November2015

Pleasecitethisarticleas:KearonC,AklEA,OrnelasJ,BlaivasA,JimenezD,BounameauxH,HuismanM,KingCS,MorrisT,SoodN,StevensSM,VintchJRE,WellsP,WollerSC,MooresCL,AntithromboticTherapyforVTEDisease:CHESTGuideline,CHEST(2016),doi:10.1016/j.chest.2015.11.026.

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ACCEPTEDMANUSCRIPT

1 WordCount:12,840

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3 AntithromboticTherapyforVTEDisease:CHESTGuideline

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CliveKearon,MD,PhD;ElieA.Akl,MD,MPH,PhD;JosephOrnelas,PhD;

AllenBlaivas,DO,FCCP;DavidJimenez,MD,PhD,FCCP;HenriBounameaux,MD;Menno

Huisman,MD,PhD;ChristopherS.King,MD,FCCP;TimothyMorris,MD,FCCP;Namita

Sood,MD,FCCP;ScottM.Stevens,MD;JanineR.E.Vintch,MD,FCCP;PhilipWells,MD;

ScottC.Woller,MD;Col.LisaMoores,MD,FCCP

10

Affiliations:McMasterUniversity(Dr.Kearon),Hamilton,ON;AmericanUniversityofBeirut

(Dr.Akl),Beirut,Lebanon;CHEST(Dr.Ornelas),Glenview,IL;VANewJerseyHealthCare

System(Dr.Blaivas),Newark,NJ;InstitutoRamónyCajaldeInvestigaciónSanitaria(Dr.

Jimenez),Madrid,Spain;UniversityofGeneva(Dr.Bounameaux),Geneva,Switzerland;Leiden

UniversityMedicalCenter(Dr.Huisman),Leiden,Netherlands;VirginiaCommonwealth

University(Dr.King),FallsChurch,VA;UniversityofCalifornia(Dr.Morris),SanDiego,CA;

TheOhioStateUniversity(Dr.Sood),Columbus,OH;IntermountainMedicalCenterandthe

UniversityofUtah(Drs.StevensandWoller),Murray,UT;Harbor-UCLAMedicalCenter(Dr.

Vintch),Torrance,CA;TheUniversityofOttawaandOttawaHospitalResearchInstitute(Dr.

Wells),Ottawa,ON;UniformedServicesUniversityoftheHealthSciences(Dr.Moores),

Bethesda,MD.

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1

Correspondenceto:ElieA.Akl,MD,MPH,PhD.AssociateProfessorofMedicine,

DepartmentofInternalMedicine,FacultyofMedicine,AmericanUniversityofBeirut,Lebanon;

ema

il:ea32@.lb

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Disclosures:Inthepastthreeyears,Dr.Aklwasanauthoronanumberofsystematicreviewson

anticoagulationinpatientswithcancer.Dr.Bounameauxhasreceivedcompensationfor

participationonadvisorycommitteeswithspeakingengagementssponsoredbySanofi-Aventis,

BayerHealthcareandDaiichi-Sankyo.Hisinstitutionhasreceivedgrantfunding(nosalary

support)fromDaiichi-SankyoforstudyingVTEtreatment.Hehasalsoservedasaco-authorof

originalstudiesusingrivaroxaban(Einstein,EinsteinPE)andedoxaban(Hokusai).Dr.Huisman

hasreceivedgrantfundingandhasdeliveredtalksrelatedtolong-termandextended

anticoagulationandtreatmentofsubsegmentalPE.Hehasalsoauthoredseveralpapersrelatedto

long-termandextendedanticoagulation,treatmentofsubsegmentalPEandcompression

stockinginpreventingpost-thromboticsyndrome.Dr.Jimenez’sinstitutionhasreceivedgrant

funding(nosalarysupport)fromInstitutodesaludCarlosIII,SociedadEspa?oladeNeumología

yCirugíaTorácica,andNeumoMadridforstudyingpulmonaryembolism.Heisamemberof

SteeringCommitteeofPEITHO,aprincipalinvestigatorofanoriginalstudyrelatedtoRoleof

IVCfilterinadditiontoanticoagulationinpatientswithacuteDVTorPEandhasparticipatedin

thederivationofscoresforidentificationoflowriskPE.Dr.Kearonhasbeencompensatedfor

speakingengagementssponsoredbyBoehringerIngelheimandBayerHealthcarerelatedtoVTE

therapy.Hisinstitutionhasreceivedgrantfunding(nosalarysupport)fromtheNIHrelatedto

thetopicofcatheterassistedthrombusremovalinpatientswithlegDVT.Hehasalsopublished

manystudiesrelatedtolong-termanticoagulationandcompressionstockingsinpreventingpost

2

thromboticsyndrome.Dr.Mooreshasfrequentlylecturedonthedurationoflong-term

anticoagulationandisaco-authoronseveralrisk-stratificationpapers.Drs.MooresandKing

havereceivedhonorariafromChestEnterprisesforVTEPrepCourses.Dr.Morris’institution

hasreceivedgrantfunding(nosalarysupport)fromPortolaPharmaceuticalsforAPEXclinical

trialrelatedtoextendedprophylaxisagainstvenousthromboembolismwithbetrixaban.Hehas

alsoauthoredtextbookchaptersrelatedtothrombolyticinterventionsinpatientswithacutePE

andpulmonarythromboendarterectomyinchronicthromboembolicpulmonaryhypertension.Dr.

Stevens’andWoller’sinstitutionhasreceivedgrantfunding(nosalarysupport)fromCanadian

InstitutesofHealthfortheD-dimerOptimalDurationStudyPhaseII(DODS-Extension),from

WashingtonUniversityviatheNationalInstitutesofHealth(GIFTTrial),BayerrelatedtoVTE

(EINSTEINstudies),andfromBristol-MyersSquibbrelatedtoapixabanfortheSecondary

preventionofThromboembolism(ASTRO-APS).Dr.Vintch’sinstitutionhasreceivedgrant

funding(nosalarysupport)fromBristol-MyersSquibbforevaluatingtheroleofapixabanfor

long-termtreatmentofVTE.Dr.Wellsisaco-investigatoronagrantregardingthetreatmentof

subsegmentalPE.Hehasauthoredseveralstudies(includingNOAC)andgrantsrelatedtothe

long-termandextendedanticoagulation.Dr.WellshasreceivedgrantfundingfromBristol-

MyersSquibbandhasreceivedhonorariafortalksfromBayer.Drs.Akl,Bounameaux,Kearon

andWellsandWollerparticipatedinthelasteditionoftheCHESTAntithromboticTherapyfor

VTEDiseaseGuidelines(AT9).Drs.Blaivas,OrnelasandSoodhavenothingtodisclose.

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66 FundingInformation:ThisguidelinewassupportedsolelybyinternalfundsfromCHEST.

67

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Endorsements:ThisguidelineisendorsedbytheAmericanAssociationforClinicalChemistry,

theAmericanCollegeofClinicalPharmacy,theInternationalSocietyforThrombosisand

Haemostasis,andtheAmericanSocietyofHealth-SystemPharmacists.

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Disclaimer:AmericanCollegeofChestPhysicianguidelinesareintendedforgeneral

informationonly,arenotmedicaladvice,anddonotreplaceprofessionalmedicalcareand

physicianadvice,whichalwaysshouldbesoughtforanymedicalcondition.Thecomplete

disclaimerforthisguidelinecanbeaccesseda

t/Guidelines-and-

Resources/Guidelines-and-Consensus-Statements/CHEST-Guidelines

77

?2015AmericanCollegeofChestPhysicians.Reproductionofthisarticleisprohibited

withoutwrittenpermissionfromtheAmericanCollegeofChestPhysicians

(

/site/misc/reprints.xhtml).

81

82 DOI:XX.XXXX/chest.XX-XXXX

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84

85

86

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87 Abstract

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Background:Weupdaterecommendationson12topicsthatwereinthe9theditionofthese

guidelines,andaddress3newtopics.

Methods:Wegeneratestrong(Grade1)andweak(Grade2)recommendationsbasedonhigh

(GradeA),moderate(GradeB)andlow(GradeC)qualityevidence.

Results:ForVTEandnocancer,aslong-termanticoagulanttherapy,wesuggestdabigatran

(Grade2B),rivaroxaban(Grade2B),apixaban(Grade2B)oredoxaban(Grade2B)overVKA

therapy,andsuggestVKAtherapyoverLMWH(Grade2C).ForVTEandcancer,wesuggest

LMWHoverVKA(Grade2B),dabigatran(Grade2C),rivaroxaban(Grade2C),apixaban

(Grade2C)oredoxaban(Grade2C).Wehavenotchangedrecommendationsforwhoshould

stopanticoagulationat3monthsorreceiveextendedtherapy.ForVTEtreatedwith

anticoagulants,werecommendagainstanIVCfilter(Grade1B).ForDVT,wesuggestnotusing

compressionstockingsroutinelytopreventPTS(Grade2B).ForsubsegmentalPEandno

proximalDVT,wesuggestclinicalsurveillanceoveranticoagulationwithalowriskofrecurrent

VTE(Grade2C),andanticoagulationoverclinicalsurveillancewithahighrisk(Grade2C).We

suggestthrombolytictherapyforPEwithhypotension(Grade2B),andsystemictherapyover

catheterdirectedthrombolysis(Grade2C).ForrecurrentVTEonanon-LMWHanticoagulant,

wesuggestLMWH(Grade2C),andforrecurrentVTEonLMWHwesuggestincreasingthe

LMWHdose(Grade2C).

Conclusion:Of54recommendationsincludedinthe30statements,20werestrongandnone

wasbasedonhighqualityevidencehighlightingtheneedforfurtherresearch.

CHEST201X;XX(X):XXXX-XXXX

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Abbreviations:AT9=The9thEditionoftheAntithromboticGuideline;AT10=The10th

EditionoftheAntithromboticGuideline;CHEST=AmericanCollegeofChestPhysicians;COI

112 =conflictofinterest;CDT=Catheter-DirectedThrombolysis;CT=ComputerizedTomography;

CTEPH=ChronicThromboembolicPulmonaryHypertension;CTPA=Computerized

TomographyPulmonaryAngiogram;DVT=deepveinthrombosis;GOC=GuidelinesOversight

Committee;INR=InternationalNormalizedRatio;IVC=InferiorVenaCava;LMWH=Low

MolecularWeightHeparin;MeSH=MedicalSubjectHeading;NOAC=non-vitaminKoral

anticoagulant;PE=pulmonaryembolism;PESI=PulmonaryEmbolismSeverityIndex;PICO=

evidencequestionsaddressingpatientpopulation,intervention,comparator,andoutcome;PTS=

Post-ThromboticSyndrome;RCT=randomizedcontrolledtrial;VKA=VitaminKAntagonist;

VTE=venousthromboembolism;UEDVT=UpperExtremityDeepVeinThrombosis;US=

Ultrasound

6

SummaryofRecommendations

NoteonShadedText:Inthisguideline,shadingisusedwithinthesummaryof

recommendationstoindicaterecommendationsthatarenewlyaddedorhavebeenchangedsince

thepublicationofAntithrombotictherapyforVTEdisease:AntithromboticTherapyand

PreventionofThrombosis,9thed:AmericanCollegeofChestPhysiciansEvidence-Based

ClinicalPracticeGuidelines.Recommendationsthatremainunchangedsincethateditionare

notshaded.TheorderofourpresentationoftheNOACS(dabigatran,rivaroxaban,apixaban,

edoxaban)isbasedonthechronologyofpublicationofthephase3trialsinVTEtreatmentand

shouldnotbeinterpretedastheguidelinepanel'sorderofpreferencefortheuseoftheseagents.

ChoiceofLong-Term(First3Months)andExtended(NoScheduledStopDate)

Anticoagulant

1. InpatientswithproximalDVTorPE,werecommendlong-term(3months)

anticoagulanttherapyovernosuchtherapy(Grade1B).

2. InpatientswithDVTofthelegorPEandnocancer,aslong-term(first3months)

anticoagulanttherapy,wesuggestdabigatran,rivaroxaban,apixabanoredoxaban

overVKAtherapy(allGrade2B).ForpatientswithDVTofthelegorPEandno

cancerwhoarenottreatedwithdabigatran,rivaroxaban,apixabanoredoxaban,we

suggestVKAtherapyoverLMWH(Grade2C).

7

Remarks:Initialparenteralanticoagulationisgivenbeforedabigatranandedoxaban,is

notgivenbeforerivaroxabanandapixaban,andisoverlappedwithVKAtherapy.See

textforfactorsthatinfluencechoiceoftherapy.

3. InpatientswithDVTofthelegorPEandcancer("cancer-associatedthrombosis"),

aslong-term(first3months)anticoagulanttherapy,wesuggestLMWHoverVKA

therapy(Grade2C),dabigatran(Grade2C),rivaroxaban(Grade2C),apixaban

(Grade2C)oredoxaban(Grade2C).

Remarks:Initialparenteralanticoagulationisgivenbeforedabigatranandedoxaban,is

notgivenbeforerivaroxabanandapixaban,andisoverlappedwithVKAtherapy.See

textforfactorsthatinfluencechoiceoftherapy.

4. InpatientswithDVTofthelegorPEwhoreceiveextendedtherapy,wesuggestthat

thereisnoneedtochangethechoiceofanticoagulantafterthefirst3months(Grade

162 2C).

Remarks:Itmaybeappropriateforthechoiceofanticoagulanttochangeinresponseto

changesinthepatient'scircumstancesorpreferencesduringthelong-termorextended

phasesoftreatment.

DurationofAnticoagulantTherapy

5. InpatientswithaproximalDVTofthelegorPEprovokedbysurgery,we

recommendtreatmentwithanticoagulationfor3monthsover(i)treatmentofa

8

shorterperiod(Grade1B),(ii)treatmentofalongertime-limitedperiod(e.g.6,12or

24months)(Grade1B),or(iii)extendedtherapy(noscheduledstopdate)(Grade

174 1B).

175

6. InpatientswithaproximalDVTofthelegorPEprovokedbyanonsurgical

transientriskfactor,werecommendtreatmentwithanticoagulationfor3months

over(i)treatmentofashorterperiod(Grade1B),and(ii)treatmentofalongertime-

limitedperiod(e.g.6,12or24months)(Grade1B).Wesuggesttreatmentwith

anticoagulationfor3monthsoverextendedtherapyifthereisalowormoderate

bleedingrisk(Grade2B),andrecommendtreatmentfor3monthsoverextended

therapyifthereisahighriskofbleeding(Grade1B).

Remarks:Inallpatientswhoreceiveextendedanticoagulanttherapy,thecontinuinguse

oftreatmentshouldbereassessedatperiodicintervals(e.g.annually).

7. InpatientswithanisolateddistalDVTofthelegprovokedbysurgeryorbya

nonsurgicaltransientriskfactor,wesuggesttreatmentwithanticoagulationfor3

monthsovertreatmentofashorterperiod(Grade2C),werecommendtreatment

withanticoagulationfor3monthsovertreatmentofalongertime-limitedperiod

(e.g.6,12or24months)(Grade1B),andwerecommendtreatmentwith

anticoagulationfor3monthsoverextendedtherapy(noscheduledstopdate)(Grade

192 1B).

Remarks:DurationoftreatmentofpatientswithisolateddistalDVTreferstopatientsin

whomadecisionhasbeenmadetotreatwithanticoagulanttherapy;however,itis

9

anticipatedthatnotallpatientswhoarediagnosedwithisolateddistalDVTwillbe

prescribedanticoagulants.

8. InpatientswithanunprovokedDVToftheleg(isolateddistalorproximal)orPE,

werecommendtreatmentwithanticoagulationforatleast3monthsovertreatment

ofashorterduration(Grade1B),andwerecommendtreatmentwithanticoagulation

for3monthsovertreatmentofalongertime-limitedperiod(e.g.6,12or24months)

(Grade1B).

Remarks:After3monthsoftreatment,patientswithunprovokedDVTofthelegorPE

shouldbeevaluatedfortherisk-benefitratioofextendedtherapy.Durationoftreatment

ofpatientswithisolateddistalDVTreferstopatientsinwhomadecisionhasbeenmade

totreatwithanticoagulanttherapy;however,itisanticipatedthatnotallpatientswhoare

diagnosedwithisolateddistalDVTwillbeprescribedanticoagulants.

9. InpatientswithafirstVTEthatisanunprovokedproximalDVTofthelegorPE

andwhohavea(i)lowormoderatebleedingrisk(seetext),wesuggestextended

anticoagulanttherapy(noscheduledstopdate)over3monthsoftherapy(Grade2B),

anda(ii)highbleedingrisk(seetext),werecommend3monthsofanticoagulant

therapyoverextendedtherapy(noscheduledstopdate)(Grade1B).

Remarks:PatientsexandD-dimerlevelmeasuredamonthafterstoppinganticoagulant

therapymayinfluencethedecisiontostoporextendanticoagulanttherapy(seetext).In

allpatientswhoreceiveextendedanticoagulanttherapy,thecontinuinguseoftreatment

shouldbereassessedatperiodicintervals(e.g.annually).

10

10. InpatientswithasecondunprovokedVTEandwhohavea(i)lowbleedingrisk(see

text),werecommendextendedanticoagulanttherapy(noscheduledstopdate)over

3months(Grade1B),(ii)moderatebleedingrisk(seetext),wesuggestextended

anticoagulanttherapyover3monthsoftherapy(Grade2B),and(iii)highbleeding

risk(seetext),wesuggest3monthsofanticoagulanttherapyoverextendedtherapy

(noscheduledstopdate)(Grade2B).

Remarks:Inallpatientswhoreceiveextendedanticoagulanttherapy,thecontinuinguse

oftreatmentshouldbereassessedatperiodicintervals(e.g.annually).

11. InpatientswithDVTofthelegorPEandactivecancer("cancer-associated

thrombosis")andwho(i)donothaveahighbleedingrisk,werecommendextended

anticoagulanttherapy(noscheduledstopdate)over3monthsoftherapy(Grade1B),

and(ii)haveahighbleedingrisk,wesuggestextendedanticoagulanttherapy(no

scheduledstopdate)over3monthsoftherapy(Grade2B).

Remarks:Inallpatientswhoreceiveextendedanticoagulanttherapy,thecontinuinguse

oftreatmentshouldbereassessedatperiodicintervals(e.g.annually).

AspirinforExtendedTreatmentofVenousThromboembolism

11

12. InpatientswithanunprovokedproximalDVTorPEwhoarestopping

anticoagulanttherapyanddonothaveacontraindicationtoaspirin,wesuggest

aspirinovernoaspirintopreventrecurrentVTE(Grade2C).

Remarks:Becauseaspirinisexpectedtobemuchlesseffectiveatpreventingrecurrent

VTEthananticoagulants,wedonotconsideraspirinareasonablealternativeto

anticoagulanttherapyinpatientswhowantextendedtherapy.However,ifapatienthas

decidedtostopanticoagulants,preventionofrecurrentVTEisoneofthebenefitsof

aspirinthatneedstobebalancedagainstaspirin'sriskofbleedingandinconvenience.Use

ofaspirinshouldalsobereevaluatedwhenpatientsstopanticoagulanttherapybecause

aspirinmayhavebeenstoppedwhenanticoagulantswerestarted.

WhetherandHowtoAnticoagulateIsolatedDistalDeepVeinThrombosis

13. InpatientswithacuteisolateddistalDVTofthelegand(i)withoutseveresymptoms

orriskfactorsforextension(seetext),wesuggestserialimagingofthedeepveins

for2weeksoveranticoagulation(Grade2C),and(ii)withseveresymptomsorrisk

factorsforextension(seetext),wesuggestanticoagulationoverserialimagingofthe

deepveins(Grade2C).

Remarks:Patientsathighriskforbleedingaremorelikelytobenefitfromserialimaging.

Patientswhoplaceahighvalueonavoidingtheinconvenienceofrepeatimaginganda

lowvalueontheinconvenienceoftreatmentandonthepotentialforbleedingarelikely

tochooseinitialanticoagulationoverserialimaging

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14. InpatientswithacuteisolateddistalDVTofthelegwhoaremanagedwith

anticoagulation,werecommendusingthesameanticoagulationasforpatientswith

acuteproximalDVT(Grade1B).

15. InpatientswithacuteisolateddistalDVTofthelegwhoaremanagedwithserial

imaging,we(i)recommendnoanticoagulationifthethrombusdoesnotextend

(Grade1B),(ii)suggestanticoagulationifthethrombusextendsbutremains

confinedtothedistalveins(Grade2C),and(iii)recommendanticoagulationifthe

thrombusextendsintotheproximalveins(Grade1B).

Catheter-DirectedThrombolysisforAcuteDeepVeinThrombosisoftheLeg

16. InpatientswithacuteproximalDVToftheleg,wesuggestanticoagulanttherapy

aloneovercatheter-directedthrombolysis(CDT)(Grade2C).

Remarks:PatientswhoaremostlikelytobenefitfromCDT(seetext),whoattachahigh

valuetopreventionofpostthromboticsyndrome(PTS),andalowervaluetotheinitial

complexity,cost,andriskofbleedingwithCDT,arelikelytochooseCDTover

anticoagulationalone.

RoleofInferiorVenaCavalFilterinAdditiontoAnticoagulationforAcuteDeepVein

ThrombosisorPulmonaryEmbolism

13

17. InpatientswithacuteDVTorPEwhoaretreatedwithanticoagulants,we

recommendagainsttheuseofanIVCfilter(Grade1B).

CompressionStockingtoPreventPost-ThromboticSyndrome

18. InpatientswithacuteDVToftheleg,wesuggestnotusingcompressionstockings

routinelytopreventPTS(Grade2B).

Remarks:Thisrecommendationfocusesonpreventionofthechroniccomplicationof

PTSandnotonthetreatmentofsymptoms.Forpatientswithacuteorchronicsymptoms,

atrialofgraduatedcompressionstockingsisoftenjustified.

WhethertoAnticoagulateSubsegmentalPulmonaryEmbolism

19. InpatientswithsubsegmentalPE(noinvolvementofmoreproximalpulmonary

arteries)andnoproximalDVTinthelegswhohavea(i)lowriskforrecurrentVTE

(seetext),wesuggestclinicalsurveillanceoveranticoagulation(Grade2C),and(ii)

highriskforrecurrentVTE(seetext),wesuggestanticoagulationoverclinical

surveillance(Grade2C).

Remarks:Ultrasoundimagingofthedeepveinsofbothlegsshouldbedonetoexclude

proximalDVT.Clinicalsurveillancecanbesupplementedbyserialultrasoundimaging

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oftheproximaldeepveinsofbothlegstodetectevolvingDVT(seetext).Patientsand

physiciansaremorelikelytooptforclinicalsurveillanceoveranticoagulationifthereis

goodcardiopulmonaryreserveorahighriskofbleeding.

TreatmentofAcutePulmonaryEmbolismOutofHospital

20. Inpatientswithlow-riskPEandwhosehomecircumstancesareadequate,we

suggesttreatmentathomeorearlydischargeoverstandarddischarge(e.g.after

first5daysoftreatment)(Grade2B).

SystemicThrombolyticTherapyforPulmonaryEmbolism

21. InpatientswithacutePEassociatedwithhypotension(e.g.systolicBP<90mmHg)

whodonothaveahighbleedingrisk,wesuggestsystemicallyadministered

thrombolytictherapyovernosuchtherapy(Grade2B).

22. InmostpatientswithacutePEnotassociatedwithhypotension,werecommend

againstsystemicallyadministeredthrombolytictherapy(Grade1B).

23. InselectedpatientswithacutePEwhodeteriorateafterstartinganticoagulant

therapybuthaveyettodevelophypotensionandwhohavealowbleedingrisk,we

15

suggestsystemicallyadministeredthrombolytictherapyovernosuchtherapy

(Grade2C).

Remarks:PatientswithPEandwithouthypotensionwhohaveseveresymptomsor

markedcardiopulmonaryimpairmentshouldbemonitoredcloselyfordeterioration.

Developmentofhypotensionsuggeststhatthrombolytictherapyhasbecomeindicated.

Cardiopulmonarydeterioration(e.g.symptoms,vitalsigns,tissueperfusion,gas

exchange,cardiacbiomarkers)thathasnotprogressedtohypotensionmayalsoalterthe

risk-benefitassessmentinfavorofthrombolytictherapyinpatientsinitiallytreatedwith

anticoagulationalone.

Catheter-BasedThrombusRemovalfortheInitialTreatmentofPulmonaryEmbolism

24. InpatientswithacutePEwhoaretreatedwithathrombolyticagent,wesuggest

systemicthrombolytictherapyusingaperipheralveinovercatheterdirected

thrombolysis(CDT)(Grade2C).

Remarks:Patientswhohaveahigherriskofbleedingwithsystemicthrombolytic

therapy,andwhohaveaccesstotheexpertiseandresourcesrequiredtodoCDT,are

likelytochooseCDToversystemicthrombolytictherapy.

25. InpatientswithacutePEassociatedwithhypotensionandwhohave(i)ahigh

bleedingrisk,(ii)failedsystemicthrombolysis,or(iii)shockthatislikelytocause

deathbeforesystemicthrombolysiscantakeeffect(e.g.withinhours),ifappropriate

16

expertiseandresourcesareavailable,wesuggestcatheterassistedthrombus

removalovernosuchintervention(Grade2C).

Remarks:Catheterassistedthrombusremovalreferstomechanicalinterventions,withor

withoutcatheterdirectedthrombolysis.

PulmonaryThromboendarterectomyfortheTreatmentofChronicThromboembolic

PulmonaryHypertension

26. InselectedpatientswithCTEPHwhoareidentifiedbyanexperienced

thromboendarterectomyteam,wesuggestpulmonarythromboendarterectomyover

nopulmonarythromboendarterectomy(Grade2C).

Remarks:PatientswithCTEPHshouldbeevaluatedbyateamwithexpertiseintreatment

ofpulmonaryhypertension.Pulmonarythromboendarterectomyisoftenlifesavingand

lifetransforming.PatientswithCTEPHwhoarenotcandidatesforpulmonary

thromboendarterectomymaybenefitfromothermechanicalandpharmacological

interventionsdesignedtolowerpulmonaryarterialpressure.

ThrombolyticTherapyinPatientswithUpperExtremityDeepVeinThrombosis

27. InpatientswithacuteUEDVTthatinvolvestheaxillaryormoreproximalveins,we

suggestanticoagulanttherapyaloneoverthrombolysis(Grade2C).

17

Remarks:Patientswho(i)aremostlikelytobenefitfromthrombolysis(seetext);(ii)

haveaccesstoCDT;(iii)attachahighvaluetopreventionofPTS;and(iv)attachalower

valuetotheinitialcomplexity,cost,andriskofbleedingwiththrombolytictherapyare

likelytochoosethrombolytictherapyoveranticoagulationalone.

28. InpatientswithUEDVTwhoundergothrombolysis,werecommendthesame

intensityanddurationofanticoagulanttherapyasinpatientswithUEDVTwhodo

notundergothrombolysis(Grade1B).

ManagementofRecurrentVenousThromboembolismonAnticoagulantTherapy

29. InpatientswhohaverecurrentVTEonVKAtherapy(inthetherapeuticrange)or

ondabigatran,rivaroxaban,apixabanoredoxaban(andarebelievedtobe

compliant),wesuggestswitchingtotreatmentwithLMWHatleasttemporarily

(Grade2C).

Remarks:RecurrentVTEwhileontherapeutic-doseanticoagulanttherapyisunusualand

shouldpromptthefollowingassessments:(1)reevaluationofwhethertheretrulywasa

recurrentVTE;(2)evaluationofcompliancewithanticoagulanttherapy;and(3)

considerationofanunderlyingmalignancy.AtemporaryswitchtoLMWHwillusually

beforatleastonemonth.

18

30. InpatientswhohaverecurrentVTEonlong-termLMWH(andarebelievedtobe

compliant)wesuggestincreasingthedoseofLMWHbyaboutone-quartertoone-

third(Grade2C).

Remarks:RecurrentVTEwhileontherapeutic-doseanticoagulanttherapyisunusualand

shouldpromptthefollowingassessments:(1)reevaluationofwhethertheretrulywasa

recurrentVTE;(2)evaluationofcompliancewithanticoagulanttherapy;and(3)

considerationofanunderlyingmalignancy.

19

CHESThasbeendevelopingandpublishingguidelinesforthetreatmentofdeepveinthrombosis

(DVT)andpulmonaryembolism(PE),collectivelyreferredtoasvenousthromboembolism

(VTE),formorethan30years.CHESTpublishedthelast(9th)editionoftheseguidelinesin

February2012(AT9).1Sincethen,asubstantialamountofnewevidencerelatingtothetreatment

ofVTEhasbeenpublished,particularlyinrelationtheuseofnon-vitaminKoralanticoagulants

(NOACs).Moreover,anumberofVTEtreatmentquestionsthatwerenotaddressedinthelast

editionhavebeenhighlighted.Thisarticlefocusesonnewdevelopmentsandongoing