SOUTHTYROLMEETING
HEARTANDBRAIN
SecondaEdizione
Prevenzionedelletromboembolie
eutilizzazionedei
nuovifarmaciAnticoagulanti.
Dr.AlessioCoser
S.C.Cardiologia‐ OspedaleS.Chiara‐ Trento
SOUTHTYROLMEETING
HEARTANDBRAIN
SecondaEdizione
Bolzano14novembre2012
FA
ictusischemicoemortalità
RR
AHAGuidelinesCirculation2001;101:2218‐50
¾Ilrischioemboliconelpazientefibrillanteè 5voltemaggiorerispettoal
pazientenonaritmico
¾Lafibrillazioneatrialeassociataavalvulopatiamitralicacomportaun
rischioembolicomoltoelevato:incidenzadistroke17voltepiù frequente
rispettoaicontrolli(Framingham)
¾Circa15‐20% deglistrokesinU.S.sonocausatidaFA
¾GliStrokesassociatiallafibrillazioneatrialesonodisolitopiù gravi,
determinanounmaggiorrischiodimorbidità emortalità eunaridotta
ripresafunzionale.
FusterV,etal.JAmCollCardiol.2006;48(4):e149‐e246. KannelWB,etal.MedClinNorthAm.2008;92(1):17‐42.
PageRL,etal.Circulation.2003;107(8):1141‐1145.DulliDA,etal.Neuroepidemiology.2003;22(2):118‐123.
StrokeeFA
™Lafibrillazioneatrialenonvalvolareè associataarischioembolicosistemicoe/o
cerebraledel5%peranno*
™Ilmaggiorrischiodistrokeè simileperlevariecategoriedifibrillazioneatriale
(parossistica,persistenteepermanente)
10
Strokerate(%/anno)
8%
8
PermanentAF
IntermittentAF
6
4
2
0
Low
Risk
Moderate
Risk
High
Risk
*FAnontrattataneglistudirandomizzati:AFASAK,SPAF,BAATAF, CAFA,SPINAF
HartRetal.JACC 2000;35:183‐187
FAecomorbidità
ATHENA:NEnglJMed2009;360:668‐678
SPORTIF:Lancet2003;362:1961‐1968
AFFIRM:NEnglJMed2002;347:1825‐1833
ALPHA:Circulation 1999;99:2328‐2335
ATRIA:JAMA 2001;285:2370‐5
Definizionedelrischiodistroke
Ilrischioindividualeditrombosisistemicaecerebraleneisoggetticonfibrillazione
atrialeè statodefinitodall’analisiretrospettivadigrandistudiclinicicontrollati(AFI,
SPAFI‐II‐III)
1°
FattoridirischioidentificatiperFAnonvalvolare(esclusa
Valvulopatiareumatica– Protesivalvolari):
•Età avanzata
•Generefemminile
•PrecedenteictusoTIA
•Ipertensionearteriosa
•Diabetemellito
•Scompensocardiacocongestizio
•Cardiopatiaischemica
Definizionedelrischiodistroke
2°
DefinizionedelPESOperciascunfattoredirischio
•HighRiskFactor
•ModerateRiskFactors
3°
Combinazionedeivarifattoriperdefinire3CATEGORIEdirischio
•HighRiskofstroke
•ModerateRiskofStroke
•LowRiskofStroke
TERAPIAOTTIMIZZATA
LOWRISK
C
DS
2
HA
2
S
A
V
‐
c
re
o
s c
INTERMRISK
HIGHRISK
CHADS2 score
Risk factor
Individual
score
None
0
C (recent CHF)
1
H (hypertension)
1
A (age) > 75 ys
1
D (diabetes mellitus)
1
S2 (hystory of stroke or TIA)
2
TAO
Ilrischiotromboembolicononè uniformemacresceesponenzialmenteconla
presenzadifattoricliniciaggiuntiviaprescinderedaltipodi FA(parox,pers
operm)
Gageetal.Validationofclinicalclassificationschemesforpredictingstroke.ResultsfromtheNational
Registryofatrialfibrillation.JAMA2001;285:2864–70.
Vantaggi CHADS2 score
• Identificacorrettamenteisoggettiadalto
rischio(score≥ 2)
• Sempliceefaciledaricordareeapplicare
Limiti CHADS2 score
• Modestac‐statistic(0,58)
• Nonstratificacorrettamenteisoggettiarischio
medio‐basso(inmoltisoggetticategorizzaticonScore1siosserva
COMUNQUEunbeneficiodellaTAOvsASA– incidenzaSIGNIFICATIVAdi
strokenelgruppo0)
2010
Pimolivello
Secondolivello
2010
Fattori di rischio
maggiori
Pregresso ictus
Pregresso TIA o episodio
embolico periferico
Età ≥75 a
Fattori di rischio
clinicamente rilevanti (non
maggiori)
Insufficienza cardiaca o disfunzione
ventricolare sn (FE ≤40%)
Ipertensione arteriosa
Diabete mellito
Età 65-74 aa
Sesso femminile
Malattie vascolari (CAD-Arteriopatia
periferica-placche aortiche complesse)
Eur Heart J 2010;31:2369-2429
CHA2DS2‐VAScscore
LipGY,FrisonL,HalperinJ,LaneD.Stroke2010Dec;41(12):2731‐8
January2003‐ October2011
589patientspresentingwithafirstIS/TIAandnon‐valvularAF(previouslyknownornewlydiagnosedduringadmission;
theAFwaspreviouslyunknownin186(31.6%).
EuropeanJournalofNeurology2013,20:623–628
STROKE/SEE
CARDIACDEATH
HijaziZ,etalJACC2013Jun4;61(22):2274‐84.
STROKE/SEE
CARDIACDEATH
HijaziZ,etalCirculation2014Feb11;129(6):625‐34.
ChronicKidneyDiseaseincreasestheriskofstroke,
bleedingandall‐causedeathinAFpatients
RiskofeventsinNVAFpatientswithnon‐end‐stageCKD(n=3587)or
withCKDrequiringrenalreplacementtherapy(n=901)comparedwith
NVAFpatientswithnorenaldisease(n=127,884)‐ Danishregistry(1997‐2008)
Reference: patients with no renal disease
HR (95% CI)*
Stroke or systemic thromboembolism
Non-end-stage CKD
1.49 (1.38; 1.59)
CKD requiring renal replacement therapy
1.83 (1.57; 2.14)
Bleeding
Non-end-stage CKD
2.24 (2.10; 2.38)
CKD requiring renal replacement therapy
2.70 (2.38; 3.07)
Myocardial infarction
Non-end-stage CKD
2.00 (1.86; 2.16)
CKD requiring renal replacement therapy
3.00 (2.58; 3.50)
Death from any cause
Non-end-stage CKD
2.37 (2.30; 2.44)
CKD*Adjustedforbaselinecharacteristics
requiring renal replacement therapy
3.35 (3.13; 3.58)
0.8
1.00
1.5
2.0
2.5
3.0
AdaptedfromOlesenetal.NEnglJMed2012;367:625‐35.
ChronicKidneyDiseaseincreasestheriskof
thromboembolisminAFpatientsnotreceivingwarfarin
ATRIAcohort(n=10,908NVAFpatientsoffwarfarin– 1995‐2003)
6
5
P<0.001fortrend
4.22
4
3
2
2.76
1.63
1
0
≥60
45‐59
<45
eGFR(mL/min/1.73m2)
ATRIA:AssemblyoftheAnticoagulationandRiskFactorsinAtrialFibrillation
eGFR:estimatedglomerularfiltrationrate
GoASetal.Circulation.2009;119:1363‐1369
ValidationoftheR2CHADS2IndexintheROCKETAFandinATRIA
(AnTicoagulationandRiskfactorsInAtrialfibrillation)StudyCohorts
CHA2DS2 +2forGFR<60
JonathanP.PicciniCirculation.2013;127:224‐232
AnderNissenBondeetal,ESC2014comunication
VALVULARvsNON‐VALVULAR
Rheumaticvalvulardisease
(predominantlymitralstenosis)
Prostheticheartvalves
“Shifttowardsgreaterfocusonidentificationof‘trulylow
risk’ patientswithAF
(whodonotneedanyantithrombotictherapy),insteadof
Antiplatelet therapy with aspirin plus
tryingtofocusonidentifying
clopidogrel, or, less effectively, aspirin
‘highriskpatients”
only, should be considered in patients
who refuse any OAC, or cannot tolerate
anticoagulants for reasons unrelated to
bleeding.
If there are contraindications to OAC or
antiplatelettherapy,leftatrialappendage
occlusion, closure or excision may be
considered.
EuropeanHeartJournal(2012)33,2719–2747
0
1
2
EuropeanHeartJournal(2012)33,2719–2747
EuropeanHeartJournal(2012)33,2719–2747
PerformanceoftheHEMORR2HAGES,ATRIA,andHAS‐BLEDBleedingRisk–
PredictionScoresinPatientsWithAtrialFibrillationUndergoingAnticoagulation
TheAMADEUSStudy
HAS‐BLEDscore
correlateswellwithICH
risk
HAS‐BLEDscore
highlightsriskfactors
thatcanbeactively
managedtoreducethe
bleedingrisk.
Apostolakisetal.JACCVol.60,No.9,2012August28,2012:861–7
P.K.MasonetalTheAmericanJournalofMedicine,Vol125,No6,June2012
R.Nieuwlaat,AmHeartJ2007;153:1006212.)
TheATAAFstudy‐ 2010
SETTINGOSPEDALIERO
TheATAAFstudy:DiPasqualeGIntJCardiol2012Aug9.[Epubaheadofprint]
L.GorinCHEST2011;140(4):911–917
LimitidellaterapiaconantagonistidellaVitaminaK
Rispostanonprevedibile
Finestraditrattamento
stretta
(INRrange2‐3)
Monitoraggioroutinario
deifattoridella
coagulazione
Lente
insorgenza/termine
d’azione
Frequentiaggiustamenti
delladose
Numeroseinterazioni
alimentari
Numeroseinterazioni
conaltrifarmaci
ResistenzaalWarfarin
1. Ansell J, et al. Chest 2008;133;160S-198S; 2. Umer Ushman MH, et al. J Interv Card Electrophysiol 2008; 22:129-137;
Nutescu EA, et al. Cardiol Clin 2008; 26:169-187.
Indicazioni
Fibrillazioneatrialenonvalvolare+unoopiù fattori:
CHADS2
•precedenteIctus,TIA,Emboliasistemica
•LVEF<40%
•NYHA≥II
•età ≥ 75anni
•età ≥ 65anniseassociataaunadellecondizioni(Diabete,
Ipertensionearteriosa,Coronaropatia)
Elegibilità allaRimborsabilità
FARMACO
PRADAXA®
(Dabigatran)
XARELTO®
(Rivaroxaban)
ELIQUIS®
(Apixaban)
CHA2DS2VASc
≥1
>3
≥1
HASBLED
>3
>3
>3
TTR
≤ 70%
≤ 60%
≤ 70%
note
(1)
(2)
(3)
(1)DeterminaAIFA20maggio2013– esuccesivirecepimenti
(2)DeterminaAIFA2agosto2013– esuccesivirecepimenti
(3)DeterminaAIFA2dicembre2013– esuccesivirecepimenti
Mitral stenosis (moderate‐severe) essentially on a rheumatic basis, is the form of AF with native
valves with the highest risk of thrombo‐embolism, probably related to the low‐flow patterns occurring in
theleftatrium;
Thepathogenesisofthrombosisismostlikelydifferentforbloodcomingintocontactwiththemechanical
prostheticvalve;
Other valvular heart diseases, such as mitral regurgitation, aortic stenosis, or aortic insufficiency, do
notresultinconditionsoflowflowintheleftatrium;
Hypertrophiccardiomyopathy,evenifpossiblyincreasingtheriskofthrombo‐embolisminAF,maynot
makethromboembolicrisklesssusceptibletoNOACscomparedwith mostformsof‘non‐valvular’ AF;
Bioprosthetic heart valve or after valve repair appears to be at a risk of thrombo‐embolism not
substantiallydifferentfrommorecommonformsof‘non‐valvular’ AF;
MARM‐AFMechanicalAndRheumaticMitralvalvularAF
Europace.2014Aug2.pii:euu178.
EurHeartJ.2014Sep28.pii:ehu352.
NOAsareShouldBePreferredtoWarfarinif…
W‐naive
W‐experienced
■LogisticinabilitytoattendINR
monitoring
■Previousischemicstroke
■Previousintracranic
haemorrage
■Youngage
■Electricalcardioversion
■LogisticinabilitytoattendINR
monitoring
■LowTTR(<60%)
■Wdailylow‐dose(8‐10mg/w)
■DrugsabletointerferewithW
andnotwithNOAs
■Previousmajorbleeding
(excludedGIbleeding)
■Previouscerebralhaemaorrage
duringWRxwiththerapeuticINR
■Previousstroke/TIAduringWRx
withtherapeuticINR
LineeGuidaAIACperlaFA.
Aggiornamento2013.
GItalCardiol2013;14:215‐40
LimitationsofNOAs
„
„
Noantidote
Lackoflaboratorytestisadouble‐edgesword
(standardmeasurementstopromoteadherence)
„
Tolerabilityandsafetyconsideration
(Follow‐upisshort)
GIbleeding
Dependanceonrenalfunction
(safetyissuesinrenalinsufficiency)
„
„
Lackofcompellingevidencethattheyarereallybetterfor
ptsdoingwellonWwithgoodINRcontrol
Nowaytoaffordthemincost‐constrainedenvironment
‐ NNT
‐ Costofthedrugvseliminationofmonitoring
2012
DabigatranMaggio‐Giugno2013
RivaroxabanAgosto‐Settembre2013
ApixabanDicembre2013‐Gennaio2014
GItalCardiol2014;15(2):99‐109
OlesenJB,etal.;Europace.2014Sep18.pii:euu225.
OlesenJB,etal.;Europace.2014Sep18.pii:euu225.
Prognosis andtreatment ofatrialfibrillation patients byEuropean cardiologists:One Year
Follow‐upoftheEURObservationalResearchProgramme‐AtrialFibrillation GeneralRegistryPilot
Phase(EORP‐AFPilotregistry).
LipGY,LarocheC,IoachimPM,RasmussenLH,Vitali‐SerdozL,PetrescuL,DarabantiuD,CrijnsHJ,
2012‐2013
KirchhofP,VardasP,TavazziL,MaggioniAP,BorianiG.
EurHeartJ.2014Aug31.pii:ehu374.[Epubaheadofprint]