Fibrilatia atriala
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Transcript of Fibrilatia atriala
Fibrilatia atrialaFibrilatia atriala
Adriana GurgheanAdriana Gurghean
Sibiu, august 2014Sibiu, august 2014
Date epidemiologiceDate epidemiologice
1,5-2% populatia generala1,5-2% populatia generala 5-15% la varstnici5-15% la varstnici 1/20 AVC acute1/20 AVC acute rriscul discul dee aparitie a FiA aparitie a FiA > 40 ani = 25%> 40 ani = 25% mai frecventa la barbatimai frecventa la barbati risc de AVC de 5x mai mare; frecvent fatalrisc de AVC de 5x mai mare; frecvent fatal risc de IC de 3x mai mare risc de IC de 3x mai mare !!!!!!
Screening FiAScreening FiA
EMBRACE & CRYSTAL-AF - EMBRACE & CRYSTAL-AF - > 1000 > 1000 pac pac
pacpac cu AVC criptogenetic cu AVC criptogenetic monitorizmonitorizatiati prelungprelungit:it: 1luna 1luna / / monitor implantabil monitor implantabil au evidentiatau evidentiat epis episoadeoade de FiA de 5x de FiA de 5x mai frecvente fata de martormai frecvente fata de martor
NEJM, june 2014
Riscul de evenimente Riscul de evenimente cardiovascularecardiovasculare
Deces cardiovascular – dubluDeces cardiovascular – dublu Insuficienta cardiaca – 30-40% si inversInsuficienta cardiaca – 30-40% si invers CM tahiaritmicaCM tahiaritmica AVC – acelasi risc pentru toate formele de FiAAVC – acelasi risc pentru toate formele de FiA Spitalizari frecvente – 1/3 spitalizarile pentru Spitalizari frecvente – 1/3 spitalizarile pentru
TRTR Disfunctie VS asimptomaticaDisfunctie VS asimptomatica Toleranta redusa la effortToleranta redusa la effort Scaderea calitatii vietiiScaderea calitatii vietii
Asocieri frecvente cu FiAAsocieri frecvente cu FiA
VarstaVarsta Insuficienta cardiacaInsuficienta cardiaca Valvulopatii – degenerativeValvulopatii – degenerative CardiomiopatiiCardiomiopatii Boli congenitale – DSA 10-15%Boli congenitale – DSA 10-15% Ischemia miocardica – 20% FiAIschemia miocardica – 20% FiA DistiroidiiDistiroidii Obezitate – 25% din FiAObezitate – 25% din FiA Diabet – 20% din FiADiabet – 20% din FiA BPOC – 10-15% din FiABPOC – 10-15% din FiA Sleep-apnoea Sleep-apnoea BCR – 10-15% din FiaBCR – 10-15% din Fia
Mecanismele de aparitie a FiAMecanismele de aparitie a FiA
disociatie intre fb mm si conducere electrica
anomalii structurale V si A
circuite mici de reintrare
initiere
perpetuare
stabilitate
MecanismeleMecanismele electrofiziologice electrofiziologice si predispozitia geneticasi predispozitia genetica
Focare anormaleFocare anormalemec celulare: automatism / reintraremec celulare: automatism / reintrarev pulm (FiA parox) / dispersate (FiA persist)v pulm (FiA parox) / dispersate (FiA persist)
Unde multipleUnde multipleconducere continua, haotica, independentaconducere continua, haotica, independenta
PredispozitiPredispozitiaa genetica genetica- - sdr QT lung / scurt; preexcitatie Vsdr QT lung / scurt; preexcitatie V- - CMHCMH- - mutatii gene: ANP, hipofct can Na, Hfct mutatii gene: ANP, hipofct can Na, Hfct
can Kcan K
Consecintele fiziopatologice Consecintele fiziopatologice ale FiAale FiA
EF: EF: ↓PRE : primele zile↓PRE : primele zile
down-reglarea curenti Ca tip Ldown-reglarea curenti Ca tip L
up-reglarea curenti rectificatori de Kup-reglarea curenti rectificatori de K
Mecanic: contractilitate ineficienta: zileMecanic: contractilitate ineficienta: zile
down-reglarea curentilor de Cadown-reglarea curentilor de Ca
scaderea eliberarii Ca din depozitescaderea eliberarii Ca din depozite
modificarea prop energetice modificarea prop energetice miofibrilaremiofibrilare
Principalele consecinte clinicePrincipalele consecinte clinice Alterarea hemodinamiciiAlterarea hemodinamicii
pierderea contractiei atrialepierderea contractiei atrialefrecventa V crescuta, neregulatafrecventa V crescuta, neregulatascaderea fluxului miocardicscaderea fluxului miocardiccardiomiopatia A si Vcardiomiopatia A si V
Accidentele tromboemboliceAccidentele tromboemboliceanomalii ale fluxuluianomalii ale fluxului: staza AS si US: staza AS si USanomalii ale componentelor sg: anomalii ale componentelor sg:
activare plachetara, hemostaza, activare plachetara, hemostaza, inflamatie, factori de ↑inflamatie, factori de ↑
ClasificareaClasificarea FiA FiA
1. Primul episod de FiA1. Primul episod de FiA – indiferent de durata / – indiferent de durata / severitatea simptomelorseveritatea simptomelor
2. FiA paroxistica2. FiA paroxistica – max 48 h – max 48 h
3. FiA persistenta3. FiA persistenta - > 7 zile / necesita cardioversie - > 7 zile / necesita cardioversie
4. FiA persistenta lunga4. FiA persistenta lunga - > 1 an - > 1 an
5. FiA permanenta5. FiA permanenta – acceptata de pacient/dr ** – acceptata de pacient/dr **
FiA asimptomatica – oricare din cele 5 forme/dg FiA asimptomatica – oricare din cele 5 forme/dg ocazional sau printr-o complicatieocazional sau printr-o complicatie
Evolutia naturala a Evolutia naturala a FiAFiA
AF = atrial fibrillation
Tipuri de FiATipuri de FiA
“ “ Lone AF’’Lone AF’’ – fara o boala cardiaca – fara o boala cardiaca structuralastructurala
FiA non-valvularaFiA non-valvulara– absenta SMi, proteze valvulare, plastie absenta SMi, proteze valvulare, plastie
VMiVMi
FiA secundaraFiA secundara– ex. infectii acuteex. infectii acute
Evaluarea clinicaEvaluarea clinica
Evaluarea simptomelor (scorul EHRA)Evaluarea simptomelor (scorul EHRA)
Estimarea riscului de AVCEstimarea riscului de AVC
Dg conditiilor predispozante pt FiADg conditiilor predispozante pt FiA
Evaluarea complicatiilorEvaluarea complicatiilor
Evaluarea clinica initialaEvaluarea clinica initiala
Momentul instalarii FiA – tip FiA
Semne de IC acuta
control urgent AV
cardioversie
eco – fct VS, PsVD, valve
AIT / AVC – CT +/- revascularizare
Evaluare risc AVC: ACO
Evaluarea cauzelor
eco cord
fctie tiroida
HLG, creat, glicemie
teste stress pt ischemie
coronarografie (persist disf)
Tratamentul Tratamentul FiAFiA
Ameliorarea simptomelorAmeliorarea simptomelorcontrolul ritmuluicontrolul ritmuluicontrolul frecventeicontrolul frecventei
Prevenirea complicatiilorPrevenirea complicatiilortratamentul antitrombotictratamentul antitrombotic
Tratamentul conditiilor Tratamentul conditiilor asociateasociate
Urgenta Urgenta !!! SEE sincron!!! SEE sincron
Controlul ritmului in FiAControlul ritmului in FiA
Cardioversia farmacologica sau electrica Cardioversia farmacologica sau electrica a a FiA FiA persistente sau supresia persistente sau supresia episoadelor recurente de FiA paroxisticaepisoadelor recurente de FiA paroxistica
!!! Mentinerea indicatiei de !!! Mentinerea indicatiei de anticoagulare chiar daca optam pentru anticoagulare chiar daca optam pentru controlul ritmuluicontrolul ritmului– Pacientii cu FiA paroxistica = acelasi risc de Pacientii cu FiA paroxistica = acelasi risc de
AVC si embolic ca si cei cu FiA persistenta !AVC si embolic ca si cei cu FiA persistenta !
Conversia electrica a FiAConversia electrica a FiA
• SEE sincron 200-360 J• Sedare / midazolam• In urgenta : simpt severe /
degradare hemodinamica / WPW• Electiva : stabili
• ACO – 3 sapt ant• FiA< 48 h - control TEE si
conversie• +/- pretratament AA
DC cardioversion for DC cardioversion for AFAF
aClass of recommendation. bLevel of evidence.AF = atrial fibrillation; DCC = direct current cardioversion.
Drugs and doses for Drugs and doses for pharmacologicalpharmacologicalconversion of (recent-onset) AFconversion of (recent-onset) AF
ACS = acute coronary syndrome; AF = atrial fibrillation; DCC = direct current cardioversion; i.v. = intravenous;N/A = not applicable; NYHA, New York Heart Association; p.o. = per os; QRS = QRS duration; QT = QT interval;T-U = abnormal repolarization (T-U) waves.
Cardioversia farmacologicaCardioversia farmacologica
Vernakalant
FiA < 7 zile / < 3 zile postinterv cardiace
Actiune: atrial
Prelungeste PRA si scade conducerea A
Instalare efect: rapida
T1/2 = 3-5 ore
Vernakalant - studiiVernakalant - studii
Superior Amiodarona
Eficient la:
HTA
Ischemie
postoperator
+/-: IC
Ineficient in: FiA > 7 zile/ FlA tipic
Vernakalant – reactii adverse si Vernakalant – reactii adverse si contraindicatiicontraindicatii
Reactii adverseReactii adverse– Hipotensiune arteriala 5-7% (16% in IC)Hipotensiune arteriala 5-7% (16% in IC)– Bradicardie 0,5%Bradicardie 0,5%– TR-V – in IC 7,3% TVNSTR-V – in IC 7,3% TVNS– Alungirea QT si QRSAlungirea QT si QRS
ContraindicatiiContraindicatii– TAs < 100 mmHgTAs < 100 mmHg– SCA < 30 zileSCA < 30 zile– IC NYHA III-IVIC NYHA III-IV– SAO severaSAO severa– QT > 440msecQT > 440msec– FE < 35 %FE < 35 %
Terapia antiaritmica oralaTerapia antiaritmica orala
I: I: preventia preventia FiA recurenta FiA recurenta (persistenta / paroxistica)(persistenta / paroxistica)
!!Eficienta vs reactii adverse si Mo !!Eficienta vs reactii adverse si Mo crescutecrescute
Controlul sControlul simptomeimptomelorlor persistente persistente date de date de recurenta recurenta FiAFiA
Antiaritmicele orale – pe ce durata Antiaritmicele orale – pe ce durata ??
Flec-SL (Flecainide Short Long)Flec-SL (Flecainide Short Long)– 635 pts, (B 64%, 64 ani, 635 pts, (B 64%, 64 ani, HFHFPEF, 6 luni)PEF, 6 luni)– 3 brate: fara AA; short (4sapt); long3 brate: fara AA; short (4sapt); long– Short: protectie 80% long la 6 lShort: protectie 80% long la 6 l
AmiodaronaAmiodarona– Long (t1/2 lung)Long (t1/2 lung)– Short (episodic) daca: r adv sint mici sau Short (episodic) daca: r adv sint mici sau
recurentele sint rarerecurentele sint rare DronedaronaDronedarona
Dronedarona in mentinerea RSDronedarona in mentinerea RS
Structura asemanatoare AStructura asemanatoare A
Blocant multiplu:Blocant multiplu:– canale Na si Kcanale Na si K– antiadrenergicantiadrenergic– prop asemanatoare Ca blocantelorprop asemanatoare Ca blocantelor
Eficienta: superior placebo/ inferior AEficienta: superior placebo/ inferior A
Dronedarona - studiiDronedarona - studii
Dronedarona – I si CIDronedarona – I si CI
I: I: – FiA paroxistica / persistenta post conv.FiA paroxistica / persistenta post conv.– IC NYHA I –II cu FE pastrataIC NYHA I –II cu FE pastrata
CI:CI:– FiA permanenta (PALLAS)FiA permanenta (PALLAS)– IC NYHA III-IV (ANDROMEDA)IC NYHA III-IV (ANDROMEDA)– Instabilitate hemodinamicaInstabilitate hemodinamica– Disfunctie sistolica VSDisfunctie sistolica VS
Choice of an antiarrhythmic Choice of an antiarrhythmic drugdrug
for AF controlfor AF control
aClass of recommendation. bLevel of evidence.AF = atrial fibrillation; AV = atrioventricular; LoE = level of evidence; NYHA = New York Heart Association.
Concluzii – terapia AA orala pt Concluzii – terapia AA orala pt controlul ritmuluicontrolul ritmului
Recurenta FiA la pacientii cu Recurenta FiA la pacientii cu AADAAD
• 77% - RFCA vs 19% - 52% - AAD !
Yun-Yu Chen, BS. 2013
LimiteLimite / complicatii ale / complicatii ale ablatiei ablatiei Limite ale eficacitatiiLimite ale eficacitatii
– FiA persistenta lunga FiA persistenta lunga (>1 (>1 anan))– AS dilatat AS dilatat (>55 mm) (>55 mm)– Age > 70 yearsAge > 70 years– Patologie structurala cardiaca Patologie structurala cardiaca – Recurente mai frecvente pe termen lungRecurente mai frecvente pe termen lung
Complicatii Complicatii
- TC, pericardita, fistula A-E, stenoza VPTC, pericardita, fistula A-E, stenoza VP- Vasculare perifericeVasculare periferice- Infarct cerebral silentios (MRI) – 4-35%Infarct cerebral silentios (MRI) – 4-35%
39
Ablatia inAblatia in FiA cu FiA cu IC IC
Eficienta neclara in IC cu Eficienta neclara in IC cu disfunctie VSdisfunctie VS
Amiodarona e I indicatieAmiodarona e I indicatie I: simptome legate de FiA I: simptome legate de FiA
sub amiodaronasub amiodarona ACO = obligatorieACO = obligatorie Rata mentinerii RS e micaRata mentinerii RS e mica Riscurile procedurale mult Riscurile procedurale mult
mai marimai mari Ameliorarea functiei VS ?Ameliorarea functiei VS ?
Ablatia pe cateter vs ablatia Ablatia pe cateter vs ablatia chirurgicalachirurgicala
Studiul FASTStudiul FAST
– A chirurgicala – eficienta > in controlul A chirurgicala – eficienta > in controlul ritmritm
– A chirurgicala - complicatii >A chirurgicala - complicatii >– Dificultati tehniceDificultati tehnice
Ablatia chirurgicalaAblatia chirurgicala
‘’‘’maze procedure’’maze procedure’’
Succes 75-95% la 15 Succes 75-95% la 15 aniani
Complic si Mo Complic si Mo crescutecrescute
FiA + BMiFiA + BMi
Evaluarea preablatieEvaluarea preablatie
Holter ECGHolter ECG
Eco cord: afectare structuralaEco cord: afectare structurala
MRI, CT: fibroza AMRI, CT: fibroza A
TEE: excludere tromb AS, USTEE: excludere tromb AS, US
ACO preablatieACO preablatie
Controlul Frecventei Controlul Frecventei in in
Fibrilatia AtrialaFibrilatia Atriala
Efectele functionale ale FiAEfectele functionale ale FiA
Pierderea pompei atrialePierderea pompei atriale– In caz de HVS reducerea volumului bataie In caz de HVS reducerea volumului bataie
cu peste 25 %cu peste 25 % Scurtarea diastolei – umplere deficitaraScurtarea diastolei – umplere deficitara Tahicardia de efort – simptome de efort Tahicardia de efort – simptome de efort Miocardiopatia tahicardicaMiocardiopatia tahicardica
Insuficienta cardiacaInsuficienta cardiaca
Cind trebuie redusa Cind trebuie redusa frecventa ?frecventa ?
Terapia initialaTerapia initiala
Pina la deciderea conversieiPina la deciderea conversiei
Prevenirea frecventei inalte in FA Prevenirea frecventei inalte in FA paroxistica si persistenta recurentaparoxistica si persistenta recurenta
FA cronicaFA cronica
Cum alegem intre controlul frecventei si controlul ritmului in FiA persistenta ?Cum alegem intre controlul frecventei si controlul ritmului in FiA persistenta ?
Quality of life
Morbidity
Mortality
Controlul ritmului vs controlul Controlul ritmului vs controlul frecventeifrecventei
Impactul FiA cronice asupra evolutieiImpactul FiA cronice asupra evolutiei
Probabilitatea de mentinere a RSProbabilitatea de mentinere a RS
Severitatea simptomatologiei legate Severitatea simptomatologiei legate de FiAde FiA
Factori ce pot influenta mentinerea Factori ce pot influenta mentinerea RSRS
Factori ce influenteaza negativ Factori ce influenteaza negativ mentinerea RSmentinerea RS
Istoric indelungat de FiAIstoric indelungat de FiA VirstaVirsta Boala cardiovasculara severa Boala cardiovasculara severa
coexistentacoexistenta ComorbiditatiComorbiditati AS dilatatAS dilatat
Cine ar beneficia cel mai mult de Cine ar beneficia cel mai mult de controlul frecventei ?controlul frecventei ?
Controlul frecventei pe termen Controlul frecventei pe termen lunglung
Controlul frecventei pe termen Controlul frecventei pe termen lunglung
AFFIRM (60-80bpm rep; 90-115bpm effort moderat)
<110bpm, rep
Care este frecventa optima ?
Controlul nefarmacologic al Controlul nefarmacologic al frecventeifrecventei
Ablatia nodului AVAblatia nodului AV– paliativa, ireversibilapaliativa, ireversibila– esecul terapiei farmacologiceesecul terapiei farmacologice
Modificarea NAV – radiofrecventaModificarea NAV – radiofrecventa– mai putin eficientamai putin eficienta
Implantare PM fctie de tipul FiA (VVI, Implantare PM fctie de tipul FiA (VVI, DDD, CRT)DDD, CRT)
Tratamentul antitrombotic Tratamentul antitrombotic in FiAin FiA
Factorii de risc tromboembolic in Factorii de risc tromboembolic in FiAFiA
Antecedente de accidente TEAntecedente de accidente TE VarstaVarsta Diabet zaharatDiabet zaharat HTAHTA Boli structurale cardiaceBoli structurale cardiace Disfunctia sistolica VS moderat-severa Disfunctia sistolica VS moderat-severa
(TTE)(TTE) Tromb prezent in AS (TEE)Tromb prezent in AS (TEE) Placi complexe Ao (TEE)Placi complexe Ao (TEE) Contrast spontan, viteze mici US (TEE)Contrast spontan, viteze mici US (TEE)
Riscul tromboembolic in FiARiscul tromboembolic in FiA (scor CHADS (scor CHADS22))
Scor 0 = risc mic
Scor 1-2 = risc moderat
Scor > 2 = risc crescut
>2 = ACO cronic
2 = istoric AVC / AIT
1 = varsta > 75 ani
HTA
IC
DZ
Limitele scorului CHADSLimitele scorului CHADS22
Categoriile de risc – mai degraba artificialeCategoriile de risc – mai degraba artificiale
Beneficii ACO vs aspirina si la cei cu risc Beneficii ACO vs aspirina si la cei cu risc moderatmoderat
Nu include multi alti FR-TE Nu include multi alti FR-TE
Majoritatea schemelor de risc cu VPP mica Majoritatea schemelor de risc cu VPP mica pt AVCpt AVC
Scorul CHAScorul CHA22DSDS22 - VASc - VASc
Aprecierea riscului hemoragicAprecierea riscului hemoragic
HEMORRHEMORR22 HAGES HAGESHepatic or renal disease, Ethanol abuse, Malignancy, Older Hepatic or renal disease, Ethanol abuse, Malignancy, Older ((>75), reduced platelet count/function, Rebleeding risk, >75), reduced platelet count/function, Rebleeding risk, Hypertension, Anemia, Genetic factors, Excessive fall risk, Hypertension, Anemia, Genetic factors, Excessive fall risk, StrokeStroke
HAS-BLEDHAS-BLEDHypertension, Abnormal liver/renal function, Stroke, Hypertension, Abnormal liver/renal function, Stroke, Bleeding history, Labile INR, Elderly, Drugs/alcoholBleeding history, Labile INR, Elderly, Drugs/alcohol
ATRIAATRIAAnTicoagulation and Risk factors In Atrial AnTicoagulation and Risk factors In Atrial fibrillationfibrillation
Terapia antitrombotica in FiATerapia antitrombotica in FiA
AspirinaAspirina
ClopidogrelClopidogrel
Antivitamina KAntivitamina K
Antitromboticele noiAntitromboticele noi
Aspirina in FiAAspirina in FiA
Metaanaliza 8 studii (4876 pts)Metaanaliza 8 studii (4876 pts)– reducerea RA cu 0,8%/an – prev Ireducerea RA cu 0,8%/an – prev I– reducerea RA cu 2,5%/an – prev IIreducerea RA cu 2,5%/an – prev II
Se prefera dozele mici (<100mg)Se prefera dozele mici (<100mg)
FiA izolata – beneficiu mic / risc FiA izolata – beneficiu mic / risc hemoragic mare (1,6% vs 0,4% hemoragic mare (1,6% vs 0,4% placebo)placebo)
Aspirina + Clopidogrel in FiAAspirina + Clopidogrel in FiA
ACTIVE-W: CLO+ASA vs WARACTIVE-W: CLO+ASA vs WAR– WAR superioara (reducere RR AVC isch cu WAR superioara (reducere RR AVC isch cu
40%)40%)– WAR – acelasi risc hemoragicWAR – acelasi risc hemoragic
ACTIVE-A: CLO+ASA vs ASAACTIVE-A: CLO+ASA vs ASA– CLO+ASA superior / risc hemoragic mareCLO+ASA superior / risc hemoragic mare
Concluzii: CLO+ASA doar daca ACO e CIConcluzii: CLO+ASA doar daca ACO e CI
Antivitamine K in FiAAntivitamine K in FiA
Reducerea RR AVC ischemic cu 67% Reducerea RR AVC ischemic cu 67% – INR terapeuticINR terapeutic
Rezultate similare pentru preventia I si Rezultate similare pentru preventia I si IIII
Reducere Mo generala cu 26%Reducere Mo generala cu 26%
Indicatie: orice FiA + cel putin 1 FR AVCIndicatie: orice FiA + cel putin 1 FR AVC
Current Trial-Associated Outcomes With Warfarin in Prevention of Stroke in Patients With Nonvalvular Atrial FibrillationA Meta-analysis
S. Agarwal et al, Arch. Intern. Med, 2012
Recomandarile pentru Recomandarile pentru profilaxieprofilaxie
Anticoagularea Anticoagularea pericardioversiepericardioversie
Anticoagularea Anticoagularea pericardioversiepericardioversie
Anticoagularea, FiA si AVC Anticoagularea, FiA si AVC acutacut
Anticoagularea, FiA si Anticoagularea, FiA si interventiile interventiile chirurgicalechirurgicale
Anticoagularea, FiA si Anticoagularea, FiA si stenturilestenturile
Anticoagularea periablatieAnticoagularea periablatie
Previne TES indiferent de FRPrevine TES indiferent de FR Nu se intrerupe/se scade daca e Nu se intrerupe/se scade daca e
nevoienevoie E recomandata postablatie pe E recomandata postablatie pe
termen lung la scor termen lung la scor > 2.> 2. ACO noi – nu exista experientaACO noi – nu exista experienta
Anticoagulantele noiAnticoagulantele noi
Inhibitori directi ai trombinei – dabigatran Inhibitori directi ai trombinei – dabigatran (RE-LY)(RE-LY)
Inhibitori directi ai factorului Xa – rivaroxaban Inhibitori directi ai factorului Xa – rivaroxaban (ROCKET-AF) / apixaban (ARISTOTLE)(ROCKET-AF) / apixaban (ARISTOTLE)
Dabigatran versus Warfarin in Patients with Atrial Fibrillation (RE-LY)
In a large, randomized trial, two doses of the In a large, randomized trial, two doses of the direct thrombin inhibitor dabigatran were direct thrombin inhibitor dabigatran were compared with warfarin in patients who had compared with warfarin in patients who had atrial fibrillation and were at risk for strokeatrial fibrillation and were at risk for stroke
Efficacy Outcomes, According to Treatment Group
Connolly SJ et al. N Engl J Med 2009;361:1139-1151
Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism, According to Treatment Group
Connolly SJ et al. N Engl J Med 2009;361:1139-1151
Rata accidentelor hemoragiceRata accidentelor hemoragice
Conclusion
In patients with atrial fibrillation, In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was dabigatran given at a dose of 110 mg was associated with rates of stroke and associated with rates of stroke and systemic embolism that were similar to systemic embolism that were similar to those associated with warfarin, as well as those associated with warfarin, as well as lower rates of major hemorrhagelower rates of major hemorrhage
Dabigatran administered at a dose of 150 Dabigatran administered at a dose of 150 mg, as compared with warfarin, was mg, as compared with warfarin, was associated with lower rates of stroke and associated with lower rates of stroke and systemic embolism but similar rates of systemic embolism but similar rates of major hemorrhagemajor hemorrhage
Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation (ROCKET-AF)
In this trial, 14,264 patients with atrial In this trial, 14,264 patients with atrial fibrillation were randomly assigned to receive fibrillation were randomly assigned to receive either rivaroxaban or warfarin.either rivaroxaban or warfarin.
Primary End Point of Stroke or Systemic Embolism.
Patel MR et al. N Engl J Med 2011;365:883-891
Cumulative Rates of the Primary End Point (Stroke or Systemic Embolism) in the Per-Protocol Population and in the Intention-to-Treat Population.
Patel MR et al. N Engl J Med 2011;365:883-891
Rates of Bleeding Events.
Patel MR et al. N Engl J Med 2011;365:883-891
Conclusions
In patients with atrial fibrillation, In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic for the prevention of stroke or systemic embolism.embolism.
There was no significant between-group There was no significant between-group difference in the risk of major bleeding, difference in the risk of major bleeding, although intracranial and fatal bleeding although intracranial and fatal bleeding occurred less frequently in the occurred less frequently in the rivaroxaban group.rivaroxaban group.
Original Article Apixaban versus Warfarin in Patients with Atrial
Fibrillation (ARISTOTLE)
N Engl J MedVolume 365(11):981-992
September 15, 2011
The oral direct factor Xa inhibitor, apixaban, was compared with warfarin in atrial fibrillation.
Apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and lowered mortality.
Kaplan–Meier Curves for the Primary Efficacy and Safety Outcomes.
Granger CB et al. N Engl J Med 2011;365:981-992
Efficacy Outcomes.
Granger CB et al. N Engl J Med 2011;365:981-992
Bleeding Outcomes and Net Clinical Outcomes.
Granger CB et al. N Engl J Med 2011;365:981-992
Conclusions
In patients with atrial fibrillation, In patients with atrial fibrillation, apixaban was superior to warfarin in apixaban was superior to warfarin in preventing stroke or systemic embolism, preventing stroke or systemic embolism, caused less bleeding, and resulted in caused less bleeding, and resulted in lower mortality.lower mortality.
rata NOAc rata WAR CI
AVC/TES 3,11% 3,79% 0,81(0,73-0,91)
AVC hemor 0,44% 0,90% 0,49(0,38-0,64)
Hemor maj 5,26% 6,17% 0,86(0,73-1)
HIC 0,70% 1,45% 0,48(0,39-0,59)
Mo generala 6,90% 7,68% 0,90(0,85-0,95)
J.Udell, Metaanaliza NOAC vs WAR, 2014
Excizia / inchiderea USExcizia / inchiderea US
TehniciTehnici– Chirurgical: Chirurgical: inin cursul interv cardiace cursul interv cardiace– Minimal invazive: epicardice / trans SIAMinimal invazive: epicardice / trans SIA
WATCHMAN / AMPLATZER CARDIAC PLUGWATCHMAN / AMPLATZER CARDIAC PLUG
RatiuniRatiuni: alternativa la ACO cronic: alternativa la ACO cronic
Limite: Limite: – Studii mici, putine, in cursStudii mici, putine, in curs– Nu toate AVC sint legate de FiANu toate AVC sint legate de FiA– Alte localizari posibile ale trombilorAlte localizari posibile ale trombilor– Nu exista comparatii intre tehniciNu exista comparatii intre tehnicile neinvazivele neinvazive
Studii Studii
PROTECT-AF: PROTECT-AF: WATCHMAN vs ACO WATCHMAN vs ACO (707 PTS)(707 PTS)– Complicatii precoce Complicatii precoce
postinterventionalepostinterventionale
PREVAIL: PREVAIL: WATCHMAN vs WATCHMAN vs WARFARINA CR (in WARFARINA CR (in curs)curs)
Terapia antiremodelareTerapia antiremodelare miocardica si fibrilatia atrialamiocardica si fibrilatia atriala
Terapia antiremodelareTerapia antiremodelare
intirzierea remodelarii intirzierea remodelarii Preventie I FiAPreventie I FiA Preventie II FiA: Preventie II FiA: ↓ratei recurentelor/ progresiei FiA↓ratei recurentelor/ progresiei FiA
Droguri cu valente antiremodelareDroguri cu valente antiremodelare
IEC / ARBIEC / ARB
antialdosteroniceantialdosteronice
statinestatine
AG polinesaturati (PUFA)AG polinesaturati (PUFA)
IEC/ARB in preventia I FiAIEC/ARB in preventia I FiA
In IC:In IC: ↓↓riscului FiA cu 30-48% in HFREF riscului FiA cu 30-48% in HFREF Nu exista evidente in HFPEFNu exista evidente in HFPEF
In HTA – rezultate neclare:In HTA – rezultate neclare:– Studii HTA: LIFE (Lo), VALUE (Val) = (+)Studii HTA: LIFE (Lo), VALUE (Val) = (+)– Studii HTA + FR: HOPE (Ram), TRANSCEND Studii HTA + FR: HOPE (Ram), TRANSCEND
(Telmi) = (-)(Telmi) = (-)
IEC / ARB in preventia II FiAIEC / ARB in preventia II FiA
1 metaanaliza: 1 metaanaliza: ↓risc recurenta cu 45-↓risc recurenta cu 45-50%50%– in asociere cu AAin asociere cu AA
CAPRAF (Candesartan in preventia FiA CAPRAF (Candesartan in preventia FiA recurente: (-) recurente: (-) – NB! fara AANB! fara AA
GISSI-AF: FiA paroxistica/GISSI-AF: FiA paroxistica/perrsistenta perrsistenta recurenta: Valsartan + AA + IEC: (-)recurenta: Valsartan + AA + IEC: (-)
Antialdosteronicele in preventia Antialdosteronicele in preventia FiAFiA
Haldosteronismul primar – risc x12 FiAHaldosteronismul primar – risc x12 FiA
FiA se asociaza cu nivel crescut aldost FiA se asociaza cu nivel crescut aldost sg.sg.
Antialdosteronicele – rol neclarAntialdosteronicele – rol neclar
Spironolactona: pare a ↓recurenta FiA Spironolactona: pare a ↓recurenta FiA postcardioversie la HTA & disfunctie VSpostcardioversie la HTA & disfunctie VS
Statinele in preventia FiAStatinele in preventia FiA
Mecanisme posibile:Mecanisme posibile:
– ameliorarea metabolism lipidicameliorarea metabolism lipidic– antiateroscleroticantiaterosclerotic– antiinflamator & antioxidantantiinflamator & antioxidant– ameliorarea disfunctiei endotelialeameliorarea disfunctiei endoteliale– ameliorarea activarii NHameliorarea activarii NH
Statinele in preventia FiAStatinele in preventia FiA
Preventia I: doar studii obs, Preventia I: doar studii obs, retrospectiveretrospective– (+): in disfunctia VS si IC(+): in disfunctia VS si IC– (-): in HTA, ischemie(-): in HTA, ischemie
Preventia II:Preventia II:– fara efecte certefara efecte certe
Postoperator: 3 studii - 17643 pacPostoperator: 3 studii - 17643 pac– ↓↓incid I episod FiA (p<0,001) incid I episod FiA (p<0,001) – efect dependent de dozaefect dependent de doza