Manejo de la anticoagulación en el manejo oncológico: DOAC ... … · The 2018 European Heart...

Manejodelaanticoagulaciónenelmanejooncológico:DOAC?Quenuevaevidenciahay?

AndrésFelipeBuitragoSandoval

Medicinainterna- cardiología- epidemiología- mastereninsuficienciacardíaca

Jefedecardiología- Jefeasociadodeldepartamentodemedicinacríticaycuidadointensivo

Situacionesenlasqueeljuiciodelindividuoylaintegridaddeunaacción,tiendenaestarindebidamenteinfluenciadoporuninterés

secundario,detipogeneralmenteeconómicoopersonal

NewEnglJMed;329(8):573-576,Ago191993

Conflictodeinterés

Conflictodeinterés…

• Investigación

• MerckSharp&Dohme,Bayer,BoehringerIngelheim,Novartis

• Speaker

• Abbott,AstraZeneca,AMGEN,ASPEN,Bayer,Boehringer

Ingelheim,Bristol-Myers&Squibb,Menarini,MerckSerono,

MerckSharp&Dohme,Novartis,Pfizer,Sanofi,Scandinavia,

Servier

• Advisoryboard

• AstraZeneca,AMGEN,BoehringerIngelheim,Bristol-Myers&

Squibb,Novartis,Pfizer

Anticoagulantes orales directos versuswarfarina

Outcomesvs.warfarin Dabigatran110mg

Dabigatran150mg Rivaroxaban Apixaban Edoxaban

60mgEdoxaban30mg

instroke/systemicembolism Non-inferiority Superiority Non-inferiority Superiority Non-

inferiorityNon-

inferiority

inischaemic/unspecifiedstroke No Yes No No No Increase

inhaemorrhagicstroke Yes Yes Yes Yes Yes Yes

inall-causedeath No No No Yes No Yes

inmajorbleeding Yes No No Yes Yes Yes

inGIbleeding No Yes Yes No Yes No

Connollyetal.NEJM2010;363:1875-6Pateletal.NEJM2011;365:883-91.3Grangeretal.NEJM2011;365:981-92

• RELY

• Recentmalignancyorradiationtherapy(within6months)andnotexpectedtosurvive3years

• Knownintracranialneoplasm,arteriovenousmalformation,oraneurysm

• ROCKETAF

• Seriousconcomitantillnessassociatedwithalifeexpectancyoflessthan2years

• ARISTOTLE

• Severecomorbidconditionwithlifeexpectancyof≤1year

• ENGAGEAF

• Activemalignancy(diagnosedwithin5years)exceptforadequatelytreatednon-melanomaskincancerorother

non-invasiveorin-situneoplasm(e.g.,cervicalcancer);

• Concurrenttreatmentwithanti-cancertherapy(drugand/orradiation);

• Lifeexpectancy<12months

Cánceryfibrilaciónauricular

The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation

Prevalencia2.4%

Incidencia1.8%

Elcáncerylaterapiaparaelcáncer:aumentanelriesgodeFA• HTA,fallacardiaca• Deshidratación,inflamaciónsistémica,aumentodeltonosimpático• Cirugíadetórax,Ibrutinib• Aumentoenlasobrevida

Edadycáncer:aumentodelriesgotromboembolicó ysangrado

Cáncerytromboembolismovenoso


Aumentodelriesgodetromboembolismo• Cerebro,páncreas,ovario,pulmón,hematológicas

Laquimioterapiaaumentaelriesgotromboembolico• Cisplatin,gemcitabine,5-fluorouracil,erythropoietin,granulocytecolonystimulatingfactors

Cancerysangrado


Infiltraciónhepática• Trombocitopeniaocoagulopatía

Tumoresmuyvascularizados• Gastrointestinal,cerebro,melanoma,célulasrenales

Neoplasiahematológicas• Coagulopatía

Tratamiento• Cirugía(herida),dañotisular(radioterapia),efectosantiproliferaticos (quimioterapia,radioterapia)

RecurrentVTE Majorbleeding*

TheChallengeofAnticoagulationinPatientswithVenousThromboembolismandCancer

RiskofeventsinpatientsreceivinganticoagulationtherapyforVTE

30

20

10

00 2 4 6 8 10 12

Cumulativeprop

ortio

nof

recurren

tmajorbleed

ing(%

)

Time(months)

CancerNo cancer

HR=2.2

12.4%

4.9%

30

20

10

00 2 4 6 8 10 12

Cumulativeprop

ortio

nof

recurren

tVTE(%

)

Time(months)

CancerNo cancer

HR=3.2

20.7%

6.8%

*Definedasovertandassociatedwitheitheradecreaseinthehaemoglobinlevel(atleast2.0g/dl)ortheneedfortransfusion(≥2unitsofblood),ifitwasretroperitonealorintracranial,orifthetreatmenthadtobediscontinuedpermanently

PrandoniPetal, Blood 2002;100:3484–3488

O’Neal,W.T.etal.JAmCollCardiol.2018;72(16):1913–22

TheAmericanJournalofMedicine(2017)130,1440–1448

CancerMedicine2017;6(6):1165–1172

VTERiskVariesOvertheNaturalHistoryofCancer

8

Chemotherapy

Risk of VTE in the cancer population

Remission

Risk of VTE in the general population

Time

Diagnosis

End of lifeHospitalization

Ris

k (o

dds

ratio

) Metastasis

Adapted from Lyman GH, Cancer 2010;7:1334–1349

7

6

5

4

3

2

1

0

IncidenceofVTEWithin2YearsofDiagnosisofFiveDifferentTypesofCancer(235,149Cases)

With regional-stage disease

Chew HK et al, Arch Intern Med 2006;166:458–464

With metastatic disease

20

15

10

5

00 100 200 300 400 500 600 700

Inci

denc

e of

VTE

(%)

Time after diagnosis (days)

PancreasLungBreastOvaryProstate

20

15

10

5

00 100 200 300 400 500 600 700

Inci

denc

e of

VTE

(%)

Time after diagnosis (days)

PancreasLungBreastOvaryProstate

CancerAssociatedThrombosisandShorterSurvival

Exposure Patient-years

Deaths Mortality per 100 patient-years (95% CI)

HR (95% CI)

None 2,777,713 1750 0.63 (0.60–0.66) 1.0 (reference)

VTE only 1317 67 5.1 (4.0–6.4) 2.6 (2.0–3.3)

Cancer only 5650 721 12.7 (11.9–13.7) 7.4 (6.8–8.2)

Cancer and VTE 131 72 55.0 (43.6–69.3) 31.2 (24.6–39.6)

CAT is related to a 30-fold increased risk of death

Timp JF et al, Blood 2013;122:1712–1723

ACCP2016:AcuteTreatmentandSecondaryPreventionofVTE

ACCP recommendation Grade of recommendation

Initial anticoagulation Acute DVT or haemodynamically stable PE and no cancer

NOAC preferred to LMWH/VKA 2BLMWH/VKA preferred to LMWH alone 2C

PE with hypotension Thrombolytic therapy (systemic rather than catheter-directed unless bleeding risk is high)

2B (2C)

DVT or PE with cancer LMWH suggested over NOAC or VKA 2CDuration of anticoagulant therapyProximal DVT or PE 3 months recommended over shorter duration 1BFirst proximal DVT or PE provoked by surgery or other transient risk factor

3 months 1B (2B if low/moderate

bleeding risk; 1B if high)Unprovoked DVT or PE Extended therapy if bleeding risk is low/moderate 2B

3 months if bleeding risk is high 1BDVT or PE associated with active cancer Extended therapy recommended over 3 months’ therapy 1B

(2B if high bleeding risk)

Kearon C et al, Chest 2016;149:315–352

EfficacyandSafetyofNOACsversusVKAintheTreatmentofCancerAssociatedThrombosis

Recurrent VTE

*Random effects modelCarrier M et al, Thromb Res 2014;134:1214–1219

Major bleeding events

0.1 1 10 0.1 1 10Lower risk with NOAC

Higher risk with NOAC

Lower risk with NOAC

Higher risk with NOAC

Study RR (95% CI) RR (95% CI)

EINSTEIN 0.64 (0.23–1.81)

Hokusai 0.52 (0.16–1.72)

RE-COVER 0.78 (0.35–1.76)

AMPLIFY 0.58 (0.14–2.34)

Combined* 0.66 (0.39–1.11)

Study RR (95% CI) RR (95% CI)

EINSTEIN 0.63 (0.22–1.79)

Hokusai 1.51 (0.37–6.17)

RE-COVER 0.82 (0.28–2.38)

AMPLIFY 0.46 (0.09–2.44)

Combined* 0.78 (0.42–1.44)

NOACs is associated with a non-significant lower risk of recurrent VTE and major bleeding episodes vs VKA

ClinOncol36:2017-2023

NEnglJMed2018;378:615-24


Quimioterapiayanticoagulantesoralesdirectos

Norelevantdrug-druginteractionanticipated

Usewithcautionoravoid

ContraindicatedduetoreducedNOACplasmalevels

Cautionisneededincaseofpolypharmacyorinthepresenceof>2bleedingriskfactors



No relevant drug -drug interaction anticipated

Use with caution or avoid

Contraindicated due to reduced NOAC plasma levels

Caution is needed in case of polypharmacy or in the presence of >_2 bleeding risk factors



Norelevantdrug-druginteractionanticipated



Cautionisneededincaseofpolypharmacyorinthepresenceof>_2bleedingriskfactors



No relevant drug -drug interaction anticipated

Use with caution or avoid





No relevant drug -drug interaction anticipatedUse with caution or avoid




QuimioterapiayanticoagulantesoralesdirectosNorelevantdrug-druginteractionanticipated




ConsiderdoseadjustmentordifferentNOACif2ormore‘yellow’factorsarepresent

contraindicated/notrecommended


QuimioterapiayanticoagulantesoralesdirectosNorelevantdrug-druginteractionanticipated




ConsiderdoseadjustmentordifferentNOACif2ormore‘yellow’factorsarepresent

contraindicated/notrecommended

ConsiderdoseadjustmentordifferentNOAC

“Noeselmásfuertedelasespecieselquesobrevive,tampocoeselmásinteligenteelquesobrevive.Esaquelqueesmásadaptablealcambio”

Charles Darwin

Gracias…

[email protected]@AFBSM

Manejo de la anticoagulación en el manejo oncológico: DOAC ... … · The 2018 European Heart...

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Transcript of Manejo de la anticoagulación en el manejo oncológico: DOAC ... … · The 2018 European Heart...