manejo de la anticoagulación en el manejo oncológico: doac ... … · the 2018 european heart...
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Manejodelaanticoagulaciónenelmanejooncológico:DOAC?Quenuevaevidenciahay?
AndrésFelipeBuitragoSandoval
Medicinainterna- cardiología- epidemiología- mastereninsuficienciacardíaca
Jefedecardiología- Jefeasociadodeldepartamentodemedicinacríticaycuidadointensivo
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Situacionesenlasqueeljuiciodelindividuoylaintegridaddeunaacción,tiendenaestarindebidamenteinfluenciadoporuninterés
secundario,detipogeneralmenteeconómicoopersonal
NewEnglJMed;329(8):573-576,Ago191993
Conflictodeinterés
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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
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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
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• 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
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Cánceryfibrilaciónauricular
The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Prevalencia2.4%
Incidencia1.8%
Elcáncerylaterapiaparaelcáncer:aumentanelriesgodeFA• HTA,fallacardiaca• Deshidratación,inflamaciónsistémica,aumentodeltonosimpático• Cirugíadetórax,Ibrutinib• Aumentoenlasobrevida
Edadycáncer:aumentodelriesgotromboembolicó ysangrado
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Cáncerytromboembolismovenoso
The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Aumentodelriesgodetromboembolismo• Cerebro,páncreas,ovario,pulmón,hematológicas
Laquimioterapiaaumentaelriesgotromboembolico• Cisplatin,gemcitabine,5-fluorouracil,erythropoietin,granulocytecolonystimulatingfactors
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Cancerysangrado
The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Infiltraciónhepática• Trombocitopeniaocoagulopatía
Tumoresmuyvascularizados• Gastrointestinal,cerebro,melanoma,célulasrenales
Neoplasiahematológicas• Coagulopatía
Tratamiento• Cirugía(herida),dañotisular(radioterapia),efectosantiproliferaticos (quimioterapia,radioterapia)
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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
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O’Neal,W.T.etal.JAmCollCardiol.2018;72(16):1913–22
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O’Neal,W.T.etal.JAmCollCardiol.2018;72(16):1913–22
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TheAmericanJournalofMedicine(2017)130,1440–1448
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CancerMedicine2017;6(6):1165–1172
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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
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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
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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
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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
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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
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ClinOncol36:2017-2023
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NEnglJMed2018;378:615-24
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Quimioterapiayanticoagulantesoralesdirectos
Norelevantdrug-druginteractionanticipated
Usewithcautionoravoid
ContraindicatedduetoreducedNOACplasmalevels
Cautionisneededincaseofpolypharmacyorinthepresenceof>2bleedingriskfactors
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Quimioterapiayanticoagulantesoralesdirectos
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
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Quimioterapiayanticoagulantesoralesdirectos
Norelevantdrug-druginteractionanticipated
Usewithcautionoravoid
ContraindicatedduetoreducedNOACplasmalevels
Cautionisneededincaseofpolypharmacyorinthepresenceof>_2bleedingriskfactors
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Quimioterapiayanticoagulantesoralesdirectos
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
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
Quimioterapiayanticoagulantesoralesdirectos
No relevant drug -drug interaction anticipatedUse 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
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
QuimioterapiayanticoagulantesoralesdirectosNorelevantdrug-druginteractionanticipated
Usewithcautionoravoid
ContraindicatedduetoreducedNOACplasmalevels
Cautionisneededincaseofpolypharmacyorinthepresenceof>_2bleedingriskfactors
ConsiderdoseadjustmentordifferentNOACif2ormore‘yellow’factorsarepresent
contraindicated/notrecommended
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
QuimioterapiayanticoagulantesoralesdirectosNorelevantdrug-druginteractionanticipated
Usewithcautionoravoid
ContraindicatedduetoreducedNOACplasmalevels
Cautionisneededincaseofpolypharmacyorinthepresenceof>_2bleedingriskfactors
ConsiderdoseadjustmentordifferentNOACif2ormore‘yellow’factorsarepresent
contraindicated/notrecommended
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
QuimioterapiayanticoagulantesoralesdirectosNorelevantdrug-druginteractionanticipated
Usewithcautionoravoid
ContraindicatedduetoreducedNOACplasmalevels
Cautionisneededincaseofpolypharmacyorinthepresenceof>_2bleedingriskfactors
ConsiderdoseadjustmentordifferentNOACif2ormore‘yellow’factorsarepresent
contraindicated/notrecommended
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The2018EuropeanHeartRhythmAssociationPracticalGuideontheuseofnon-vitaminKantagonistoralanticoagulantsinpatientswithatrialfibrillation
QuimioterapiayanticoagulantesoralesdirectosNorelevantdrug-druginteractionanticipated
Usewithcautionoravoid
ContraindicatedduetoreducedNOACplasmalevels
Cautionisneededincaseofpolypharmacyorinthepresenceof>_2bleedingriskfactors
ConsiderdoseadjustmentordifferentNOACif2ormore‘yellow’factorsarepresent
contraindicated/notrecommended
ConsiderdoseadjustmentordifferentNOAC
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“Noeselmásfuertedelasespecieselquesobrevive,tampocoeselmásinteligenteelquesobrevive.Esaquelqueesmásadaptablealcambio”
Charles Darwin
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