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