A stroke risk reduction of 69% attributable to warfarin was seen when the data from five studies were combined in the pooled analysis. All analyses represented for individual studies are done on an “intention-to-treat” basis. Note: Strokes represent all strokes regardless of suspected etiology. Transient ischemic attacks, systemic emboli and intracranial hemorrhages are not included. Control represents placebo in all studies except BAATAF where 46% of “control” patients received aspirin and 54% received no treatment. 20
Background: Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage. Objective: To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation. Design: Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003. Setting: An integrated health care delivery system. Patients: 13 559 adults with nonvalvular atrial fibrillation. Measurements: Warfarin exposure, patient characteristics, CHADS2 score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism. Results: Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS2 stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS2 categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used. Limitations: Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable. Conclusion: Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation.
Reference Kubitza D and Haas S. Expert Opin Investig Drugs 2006;15:843–855
And in pts with chronic atrial fibrillation, As you can see, the overall efficacy of these medications in terms of maintaining sinus rhythm at 6 months range between 40-60%. I tell all my patients who I start on AAD that AF is going to come back. (Define AAD failure).
Not only that , but the potential negative side effects result in a relatively high discontinuation rate. If you look at this for example you see that amiodarone has a relatively high discontinuation rate, almost 20% at 6 months stop taking it, mostly because of its extracardiac side effects. It can affect the thyroid, the liver, the lung, the skin , the eyes and the CNS. This is why we tend to avoid it in young patients unless you want them to end up as blue cretins, wheeezing and limping but in NSR.
And some of the side effects are actually serioutransform AF into AFs and fatal. Such as what you see with the use of class 3 AAD such as sotalol or dofetilide. Similarly, patients with structural heart disease cannot be treated with class I antiarrhythmic such as flecainide or propafenone because of the risk of proarrhtyhmia such as VF. Even in patients with no structural heart disease, class IC drug can transform atrial fibrillation into AFl which is slow enough to conduct 1:1 to the V and result into a WCT that resembles VT and can actually degenerate into VF.
This has changed significantly our understanding of atrial fibrillation. Indeed the natural history of AF is to procced from intermittent self terminating episodes episodes of AF to a more persistent form requiring frequent DC cardioversions over time to finally telling the patient that there is not much that we can do about it and that they have to spend the rest of their lives in AF. And we know why this happens And there is a good reason for this to happen. With more atrial fibrillation, there is a change in the electrophysiologic environment of the atria, or atrial remodeling which occur which favors reentry. So, our understanding of atrial fibrillation has changed. We havetriggers,which are rapid firing recorded within the PV that propagagte tto the atrium. If the electrophysiologic environment in the atrium is suitable for sustaining AF, what is commonly known as F conduction, the AF persists, if not then AF terminates or never starts. This is what happens initially we have paroxysms of AF: it strats/ stops because the substrate is not ready for AF yet. But with more and more paroxysms and with some modulating factors, Athere are changes in the EP properties of the atria which favor reentry and tend to be more inviting for sustaining AF. What triggers PV firing? We do not know: is it automaticity, EAD with TDP like phenomenon in the atria, is it only one impulse with circual conduction that is rapid or leakage from the rapid firing of the SM cells in the wall of the veins: we do not know yet. that start off AF. and a or which start of AF and it is up to the atrial substarte to mintain AF or not. a substarate. initiators, perpetuators and underlying substarte. What is responsible for the firing within the PV? For some reason some people have a substrate for triggers which cause the rapid firing seen in the PV ’s. Initially this is usually paroxismal in nature. The atrial substarte is not mature for AF to settle in yet.It is like trying to start a car in a cold wheather you try many times but it doesn’t start. With time atrial remodeling occurs and with the help of other factors such as …, the atrial substrate becomes more inviting for permanent atrial fibrillation. And there might be some erpetuators in the meantime such as intermittent ongoing PV activity which tends to cause ongoing AF.
In this presentation, will show the 1050 pt-yr data
Dr. Eduardo Saad: Fibrilação atrial: O que há de mais moderno.
Eduardo B. Saad, PhD, FHRSCoordenador do Serviço de Arritmias e Estimulação CardíacaCentro de Fibrilação AtrialHospital Pró-Cardíaco - Rio de JaneiroHospital Samaritano - Rio de JaneiroFibrilação Atrial em 2013:O Que Há de Mais Modernofirstname.lastname@example.org
Epidemiologia da Fibrilação Atrial:ATRIA Study5,615,425,164,784,343,803,332,942,662,442,262,0801234561995200020052010201520202025203020352040204520502060YearAdultswithAF,MMProjeção de Adultos com FA nos EUA: 1995 to 2050.Go A, et al. JAMA. 2001;285:2370-2375.
Impact of Atrial Fibrillation on the Risk of DeathThe Framingham Heart Study(N: 5209; 55 a 94 anos; : 40 years)A FibM: 61.5%F: 57.6%O.R. = 1.5 - 1.9No A FibM: 30.0%F: 20.9%(55 a 74 anos)
AFASAKAFASAK 2727 811811BAATAFBAATAF 1515 922922CAFACAFA 1414 478478SPAFSPAF 2323 508508SPINAFSPINAF 2929 972972Combined*Combined* 108108 36913691No. ofNo. ofEventsEventsPatient-Patient-yearsyears100% 50% 0100% 50% 0 -50-50% -100%% -100%Warfarin BetterWarfarin Better Warfarin WorseWarfarin WorseRisk Reduction, %Risk Reduction, %*Total risk reduction for all 5*Total risk reduction for all 5studies combined is 69%studies combined is 69%Eficárica da Warfarina na Prevenção de AVE
Benefício da Warfarina:Impacto da idadeSinger D, Ann Int Med. 2009; 2009;151:297-305.
Dificuldades com o uso da Warfarina• Janela terapêutica estreita– Monitorização frequente• Risco de sangramento– Hemorragia intracraniana• Interações com drogas ealimentos• Relutância em prescrever empacientes idosos– Risco de queda– Aderência duvidosa
XVIIaTFIXIXaFibrinogenio FibrinaII ProtrombinaINICIAÇÃOPROPAGAÇÃO=Fase de geração detrombinaFORMAÇÃO DO COÁGULOFator InativoFator AtivoTransformaçãoCatáliseLegendaXa VaComplexoProtrombinaseRivaroxabana,apixaban,edoxabanIIa Trombina DabigatranNovos Anticoagulantes
Novos Anticoagulantes- Efeito dose dependente- Dispensa a monitorização com exames laboratoriais- Dose única ou duas tomadas diárias- Poucas interações medicamentosas ou com alimentos- Estudos randomizados controlados com grandenúmero de pacientes- Cuidados!!!1. Verificar a função renal2. Não há como reverter o efeito rapidamente
Manutenção do RitmoSinusal:O que há de mais moderno?
Manutenção do Ritmo SinusalNEJM 2000; 342:913-20
Eficácia das Drogas Antiarrítmicaspara Tratamento da FARitmo Sinusal(%)Sem droga 31 (15-56)Quinidina 41 (11-54)Disopiramida 49 (44-54)Propafenona 39 (30-46)Studies followed patients at least 6 months after cardioversion (adapted from Crijns)IaIaIcIcIIIIII~50%-60%~50%-60%Ritmo SinusalRitmo Sinusal
020406080100Non Drug Quinidine FlecainidePropafenone Sotalol AmiodaroneEfficacyDiscontinuationFA: Drogas AntiarrítmicasStudies followed patients at least 6 months after cardioversion (adapted from Crijns)30%30%Taxa de SuspensãoTaxa de Suspensão
Torsade de PointesAtrial Flutter1:1 AV conductionEF 25% CAD
J Cardiovasc Electrophysiol 2008; 19: 1220-26Modificação da molécula daAmiodarona:-Ausência de Iodo-Menos lipofílico – menor acúmulotecidial-Meia vida – 1-2 dias (vs 30-55dias – Amiodarona)
67%77%Recorrência - 96 dias vs 41dias NEJM 2007; 357: 987-99828 pt - Dronedarona 400 mgbid409 pt - PlaceboSem diferenças em efeitoscolaterais – pulmão, tireóidee fígadoAumento da incidência dedisfunção renal (2,4% vs0,2%)
Ablação de FAWilber et al, JAMA, 201063%17%All Recurrent AT/AFSymptomatic AT/AF70%19%Safety• Ablation Group (6.8%, n=103)– 1 pericarditis– 1 pulmonary edema–1 pericardial effusion (no tx needed)– 5 vascular complications– No Stroke/Embolism, Tamponade,Atrio-Esophageal fistula, PV stenosis,or Phrenic nerve paralysis• AAD group (17.9%, n=56)– 3 life-threatening ventriculararrhythmias– 7 disabling symptoms requiringdrug withdrawal• One death in Ablation group, at 284days, due to acute MI.
Circulation 2008; 118: 2498-250589%23%- Média de 1,8 ± 0,8ablações/pt- 2,5 ± 1 droga/pt- 75% com recorrênciaapesar do uso de drogaclasse III- Amiodarona - recorrênciade FA em 66%- 63% crossover paraablação
Recorrências Tardias de FARecorrências Tardias de FAOuyang F et al. Circulation 122:2368, 2010Multiple ProcedureSuccessSingle ProcedureSuccessWeerasooriya R et al. JACC 57:160, 2011Singe ProcedureSuccessMultiple ProcedureSuccess
História Natural da FAParoxísticaTerminaçãoespontâneaPermanenteNão conseguereverterPersistenteRitmo sinusal comcardioversão elétricaou químicaGatilhoGatilhoIniciaçãoIniciaçãoSubstratoSubstratomanutençãomanutenção
Heart Rhythm 2009; 6: 1403-14121404 pt com FA:Ablação guiada por ICE12 operadores4 centrosFollow-up médio: 57 ± 17 meses78%67%1aablaçãoImpact of Type of Atrial Fibrillation and Repeat CatheterAblation on Long-Term Freedom from Atrial Fibrillation:Results from a Multicenter Study
Saad E at al. Circ Arrhythm Electrophysiol 2011; 4:615-
ResultadosComplicações Cerebrovasculares:-AVE isquêmico - 0- suspensão de DAA em 293 pt (89,6%)- suspensão do ACO em 298 pt (91,1%)-AVE hemorrágico -3 pt (0,9%)- durante ACO (2, 9 e 11 meses após ablação)- Sequelas motoras em todos os pt- 1 pt - cirurgia descompressiva
Risco de sangramento maior no primeiro anoapós o início da warfarina em idosos• 65 - 79 anos = 4.2%• ≥80 anos = 10.7%• Maior CHADS2 =maior risco desangramentos• (quase 10x de score 0 a ≥4)Circulation 2007;115;2689> 80 y< 80 yUso de Anticoagulante Oral em PacientesIdosos
Annals of Internal Medicine, 1999; 131(12): 927-934020406080<55<55 55-6455-64 65-7465-74 75-8475-84 >85>8544%44%58%58% 61%61%57%57%35%35%Age (years)Age (years)WarfarinUseinWarfarinUseinEligiblePatients(%)EligiblePatients(%)55%55%OveralOverall Usel UseBaixo uso da Warfarina
23 estudos- 2208 auriculetas examinadas emautópsia, ETE ou intra-operatório: 13% dos pt com trombo no AE AF valvar: 57% na auriculeta FA não-valvar: 90% na auriculetaStroke 2007;38:624-30Background