FIBRILLAZIONE ATRIALE NEI PAZIENTI CON ICTUS

Transcription

1 FIBRILLAZIONE ATRIALE NEI PAZIENTI CON ICTUS Riunione Commissione Regionale Stroke Care Bologna, 3 Novembre 2010 Giuseppe Di Pasquale Unità Operativa Cardiologia Ospedale Maggiore, Bologna

2 Mechanism Subtype Prevalence Borderzone 5 % Lacunar 20 % Cryptogenic and rare causes 20 % Artery-to-artery embolism 20 % Aortic arch atheroma 15 % Cardiac embolism 20 %

3 Mechanism Subtype Prevalence Borderzone 5 % Lacunar 20 % Cryptogenic and rare causes 20 % Artery-to-artery embolism 20 % Aortic arch atheroma 15 % Cardiac embolism 20 %

4 Cardioembolic Sources Valvular heart disease Prosthetic valves 10% 5% LV thrombus 10% 10% Acute MI 15% 50% Other less common sources (PFO, ASA, aortic debris, etc.) Nonvalvular Atrial Fibrillation Cerebral Embolism Task Force, Arch. Neurol 1986;43:71-84

5 STROKE CARDIOEMBOLICO (n=466) FA di nuova diagnosi n=156 Fibrillazione Atriale e Stroke Stroke Unit Ospedale Maggiore Casistica % 8% Altre cause (n=50) 33% 11% 33% 21% 26% 35% FA persistente n=164 Anamnesi di FA parossistica n=96

6 Fibrillazione Atriale e Stroke Entità del rischio Studio Framingham Prevalenza FA Stroke secondari a FA % Età (anni) Wolf PA et al. Stroke 1991;22:983-8

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8 FA aumenta il rischio di ictus grave Il rischio di ictus èaumentato indipendentemente dal tipo di FA (parossistica vs. persistente) 1,2 Gravità dell ictus in paziente con FA Effetti di un primo ictus ischemico in paziente con FA (n=597) 1 60% 50% % di pazienti 40% 30% 20% 10% 0% Disabilità Morte 1. Gladstone DJ et al. Stroke. 2009; 40: Rosamond W et al. Circulation. 2008;117:e25 146; 2.Hart RG, et al. J Am Coll Cardiol 2000;35: ;

9 Stroke cardioembolico Outcome Stroke Unit Ospedale Maggiore Casistica DIAGNOSI N % DECESSI N % Accessi ischemici transitori 141 7% 0 - Emorragia (tipica) 188 9% 52 28% Emorragia (lobare) 113 5% 38 34% Ictus atero-trombotico % 22 10% Ictus cardio-embolico % 92 20% Ictus lacunare % 4 1% Ictus di incerta eziologia % 70 14% Ictus da altre cause 88 4% 9 10% TOTALE % %

10 ATRIAL FIBRILLATION AND STROKE The risk of stroke is not the same among the patients with AF

11 Non valvular Atrial Fibrillation Stroke Rates Without Anticoagulation According to Isolated Risk Factors Stroke Rate (% year) Prior Stroke/TIA Age >75 years Hypertension Female Diabetes Heart Failure LVEF Hart RG et al. Neurology 2007; 69: 546

12 Rischio di di recidive e mortalitàa due anni, per tipo di di ictus (n=531) Epidemiologyof Epidemiologyof ischemicstrokesubtypesaccordingtotoast ischemicstrokesubtypesaccordingtotoast criteria: criteria: incidence, incidence, recurrence, recurrence, and and long-termsurvivalin long-termsurvivalin ischemicstrokesubtypes: ischemicstrokesubtypes: a a population-basedstudy. population-basedstudy. PL PL Kolominsky-Rabasetal.Stroke. Kolominsky-Rabasetal.Stroke. 2001;32: ;32:

13 Mechanism Subtype Prevalence Borderzone 5 % Lacunar 20 % Cryptogenic and rare causes 20 % Artery-to-artery embolism 20 % Aortic arch atheroma 15 % Cardiac embolism 20 %

14 Fibrillazione Atriale nei Pazienti con Stroke 20% 80%

15 AF monitoring after cryptogenetic stroke Pts. with AF detected (%) ,8 11,8 17,5 5 2,7 0 1 ECG Multiple ECGs 24 h Holter 7 d Holter D. Jabaudon. Stroke 2004; 35:

16 Intermittent AF may account for a large proportion of otherwise cryptogenic stroke A study of 30-day cardiac event monitor Conclusion: The 30-DEM changed the medical treatment of 20% of patients with otherwise cryptogenic stroke because of the detection of intermittent AF despite no detection of AF on electrocardiographyand in patient telemetry monitoringin the majority of patients. Elijovich et al. J of Stroke and Cerebrovascular Diseases 2009

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18 Newly Detected AF and Previous Stroke Ziegler P et al. Stroke 2010;41:256-60

19 Prevalence of Asymptomatic AF (%) Discovered incidentally/ ECG DuringAAD Therapy/ TTEM PM ICD recipients/ Devicememory Post-AFAblation/ TTEM, 7-d Holter, 0-20

20 Profilassi antritrombotica della fibrillazione atriale: Le evidenze

21 RELATIVE EFFECTS OF ANTITHROMBOTIC THERAPIES ON ALL STROKE FROM RANDOMISED TRIALS IN AF Warfarin Relative RR vs. placebo 64% (CI 49 74) Absolute risk reduction primary 2.7%/yr Absolute risk reduction secondary 8.4%/yr NNT primary prevention 37 NNT secondary prevention 12 ASA Relative RR vs. placebo 19% (CI -1 35) Absolute risk reduction primary 0.8%/yr Absolute risk reduction secondary 2.5%/yr NNT primary prevention 125 NNT secondary prevention 40 Warfarin vs ASA Relative RR 37% (CI 23 48) B Study, Year Relative Risk Reduction C Study, Year Relative (95% Risk Reduction CI) AntiplateletA Study, Year agents compared with Relative (95% Risk CI) Reduction placebo or control (95% CI) Adjusted-dose AFASAK I, 1989; warfarin 1990 compared with antiplatelet agents Adjusted-dose SPAF I, 1991 warfarin compared AFASAK with EAFT, placebo 1993 I, 1989; 1990 or control AFASAK ESPS II, II, Chinese LASAF, AFASAK ATAFS, 1997 I, 1989; EAFT, Daily SPAF 1993 I, 1991 PATAF, Alternate 1999day UK-TIA, BAATAF, SPAF II, 1994 CAFA, 300 mg 1991 daily Age 75 y 1200 mg daily JAST, SPINAF, Age > y EAFT, Aspirin 1993 trials (n=7) (n=8)* SIFA, SAFT, ACTIVE-W, ESPS All trials II, (n=6) Dipyridamole NASPEAF, 2004 Combination All antiplatelet trials (n=11) 100% 50% 0-50% -100% All antiplatelet trials (n=8) Favours Warfarin Favours Placebo 100% 50% 0 100% 50% or -50% -50% Control -100% -100% Favours Warfarin Favours Antiplatelet Favours Antiplatelet Favours Placebo or Control Hart RG et al. Ann Intern Med 2007;146:857 67

22 Antithrombotic Therapy for AFib Stroke Risk Reduction Treatment Better Treatment Worse Warfarin vs. Placebo/Control -64% 6 Trials n = 2,900 Antiplatelet drugs vs. Placebo -19% 8 Trials n = 4, % 50% 0-50% Hart R et al. Ann Intern Med 2007; 146: 857

23 Rates of Stroke with AF in Patients Treated with Antithrombotics Antiplatelets Stroke Rate % per Year No treatment 4.5 Placebo arm 5 RCT 2.4 ATRIA Cohort 7.9 SPAF III Aspirin + miniw 2.2 ACTIVE-W Aspirin + Clopidogrel 1.9 SPAF III Warfarin Anticoagulants SPORTIF V Warfarin ACTIVE-W Warfarin Trials Trials RE-LY Dabigatran 150 mg x 2

24 Effect of Intensity of Oral Anticoagulation on Stroke Severity and Mortality in Atrial Fibrillation Elaine M. Hylek, M.D., M.P.H., Alan S. Go, M.D., Yuchiao Chang, Ph.D., Nancy G. Jensvold, M.P.H., Lori E. Henault, M.P.H., Joe V. Selby, M.D., M.P.H., and Daniel E. Singer, M.D. N Engl J Med, September 11, 2003

25 30-Day Survival after an Ischemic Stroke among Patients with Nonvalvular Atrial Fibrillation Hylek EM et al. N Engl J Med 2003; 349:

26 Profilassi antritrombotica della fibrillazione atriale: Il mondo reale

27 Oral Anticoagulation for Atrial Fibrillation Underutilization of Warfarin in Clinical Practice 100 ATRIA Study Warfarin Use in Eligible Patients (%) % 58% 61% 57% 35% 55% Overall Use 0 < > 85 Age (years) Go A et al. Ann Intern Med 1999; 131:

28 Missed Opportunities for Stroke Prevention in Atrial Fibrillation Preadmission medications in patients with known AF admitted with acute ischemic stroke No antithrombotics 29% Warfarintherapeutic 10% Warfarinsubtherapeutic 29% Dual antiplatelet therapy, 2% Single antiplatelet agent, 29% Gladstone DJ et al., Stroke 2009;40:

29 No antithrombotics 29% Fibrillazione Atriale e Stroke Missed Opportunities for Stroke Prevention in AF Preadmission medications in patients with AF admitted with acute ischemic stroke 597 pts with known AF (high risk and no contr.) 260 pts with known AF W Therapeutic 10% No anthithrombotics 30% W Therapeutic 6% W Subtherapeutic 18% Dual antiplat therapy, 2% Single antiplatelet agent, 29% W subtherapeutic 29% Single Antiplatelet agent 46% Gladstone DJ et al., Stroke 2009; 40: Stroke Unit Ospedale Maggiore, Bologna

30 The Promise of New Anticoagulants

31 New Anticoagulants Initiation X Coagulation cascade TF/VIIa IX Drug Tissue factor pathway inhibitors: NAPc2 Propagation Thrombin activity Fibrinogen VIIa IXa Xa Va II IIa Fibrin Indirect: fondaparinux, idraparinux Direct Oral: rivaroxaban, apixaban, edoxaban Direct Parenteral: bivalirudin Direct Oral: ximelagatran, dabigatran,, AZD0837

32 Atrial Fibrillation Phase 3 Study Timelines Dabigatran RE-LY Estimated completion March 2009 Rivaroxaban ROCKET Estimated completion June AVERROES estimated completion April 2010 ARISTOTLE Estimated completion November 2010 Apixaban ClinicalTrials.gov. Accessed February 27, 2009.

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34 Lancet Neurology, 8 November 2010

35 Risk of stroke/se is higher in patients with prior TIA or stroke Prior stroke/tia: time to primary outcome No prior stroke/tia: time to primary outcome Cumulative Hazard Rates # at Risk Year D D W Dabigatran 110 mg Years of follow-up Warfarin Dabigatran 150 mg Cumulative Hazard Rates # at Risk Year D D W Dabigatran110 mg Years of follow-up Warfarin Dabigatran150 mg Dabigatran etexilate is in clinical development and not licensed for clinical use in stroke prevention for patients with atrial fibrillation Dabigatran etexilate is in clinical development and not licensed for clinical use in stroke prevention for patients with atrial fibrillation

36 Intra-cranial bleeding rates in patients with prior stroke or TIA 30 RR 0.20 (95% CI: ) p<0.001 RR 0.41 (95% CI: ) P= Number of events RRR 80% 13 RRR 59% 6 0 D110 mg bid D150 mg bid Warfarin Dabigatran etexilate is in clinical development and not licensed for clinical use in stroke prevention for patients with atrial fibrillation

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38 Percutaneous and surgical interventions for the prevention of stroke in patients with AF

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40 Left Atrial Appendage Role Because 60 to 90% of stroke-causing emboli in AF patients originate from the left atrial appendage, this structure has been termed our most lethal human attachment. Therefore, excision or exclusion of the left atrial appendage is a critical component of operations to manage AF; this may explain in part the exceedingly low risk of stroke after the Maze procedure. Johnson WD, Ganjoo AK, Stone CD, et al. The left atrial appendage: our most lethal human attachment! Surgical implications. Eur J Cardiothorac Surg 2000; 17: Garcia-Fernandez MA, Perez-David E, Quiles J, et al. Role of left atrial appendage obliteration in stroke reduction in patients with mitral valve prosthesis: a transesophageal echocardiographic study. J Am Coll Cardiol 2003; 42:

41 WATCHMAN LAA Closure Device in situ

42 PLAATO Delivery System

43 Percutaneous Left Atrial Appendage Transcatheter Occlusion to Prevent Stroke in High-Risk Patients With Atrial Fibrillation Early Clinical Experience Horst Sievert,, MD; Michael D. Lesh,, MD; Thomas Trepels; Heyder Omran,, MD; Antonio Bartorelli,, MD; Paolo Della Bella, MD; Toshiko Nakai,, MD; Mark Reisman,, MD; Carlo DiMario,, MD; Peter Block, MD; Paul Kramer,, MD; Dirk Fleschenberg; Ulrike Krumsdorf; Detlef Scherer,, MD. Circulation 2002;105:

44 LET S CLOSE IT! Percutaneous Left Atrial Appendage Transcatheter Occlusion PLAATO

45 79 yrs-old old,, male, chronic AFib,, HTN, previous TIAs Refractory GI bleedings with warfarin PLAATO Implantation Initial Experience at Maggiore Hospital, Bologna Pre-Implant

46 Device Expansion TEE Echo After Implant

47 Successful implantation No Complications No failures after 3-years follow-up PLAATO Implantation Initial Experience at Maggiore Hospital, Bologna Final Result

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50 239.9 Pts-year

51 Lancet 2009;374:534-42

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55 Mechanism Subtype Prevalence Borderzone 5 % Lacunar 20 % Cryptogenic and rare causes 20 % Artery-to-artery embolism 20 % Aortic arch atheroma 15 % Cardiac embolism 20 %

56 Fibrillazione Atriale nei Pazienti con Stroke 20% 80%

57 AF monitoring after cryptogenetic stroke Pts. with AF detected (%) ,8 11,8 17,5 5 2,7 0 1 ECG Multiple ECGs 24 h Holter 7 d Holter D. Jabaudon. Stroke 2004; 35:

58 Intermittent AF may account for a large proportion of otherwise cryptogenic stroke A study of 30-day cardiac event monitor Conclusion: The 30-DEM changed the medical treatment of 20% of patients with otherwise cryptogenic stroke because of the detection of intermittent AF despite no detection of AF on electrocardiographyand in patient telemetry monitoringin the majority of patients. Elijovich et al. J of Stroke and Cerebrovascular Diseases 2009

59 Prevalence of Asymptomatic AF (%) Discovered incidentally / ECG During AAD Therapy / TTEM PM ICD recipients / Device memory Post-AF Ablation / TTEM, 7-d Holter, 0-20

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61 Newly Detected AF and Previous Stroke Ziegler P et al. Stroke 2010;41:256-60

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63 Lancet Neurology, 8 November 2010