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Sutikno Tanuwidjojo Bagian Kardiologi & Kedokteran Vaskular / Sub. Bagian Kardiologi Bag. Penyakit Dalam FK. UNDIP / RS. Dr. Kariadi Semarang
AF is the most common sustained tachyarrhythmia leading to substantial morbidity and mortality from thromboembolism (stroke) and heart failure. AF has been considered to be the epidemic of the new millennium, its incidence increases with age and with the presence of heart disease AF is associated with a 2-fold increase in cardiac mortality It is associated with a 5-fold increased risk of stroke in the absence of adequate anticoagulation therapy
JAMA.The Probability of Developing AF Increases With Age 12 Prevalence ( % ) 10 8 6 4 2 0 <55 55-59 60-64 65-69 70-74 75-79 80-84 >85 Women Men Go et al. 2001.285:2370-2375 .
Leading Circle Reentry 50 30 10 130 6 110 5 190 1 50 4 2 3 30 Ectopic Foci Right Atrium Superior Vena Cava Septum 17 Left Atrium 31 Pulmonary Veins 110 Inferior Vena Cava Fossa Ovails 6 11 170 150 1 250 6 210 4 2 3 190 170 250 230 210 Coronary Sinus n = 45 pts 230 5 The Mechanisms Underlying Human AF .
2004) .Pathophysiology of Atrial Fibrillation ? Inflammation • Mitral stenosis / regurgitation • compliance Atrial dilatation/stretch • LVH • Diastolic dysfunction stretch-activated channels ? Inflammation dispersion of refractoriness pulmonary vein focal/discharges? Increased vulnerability to atrial pathophysiology of AF Hypothetical construct of the pathophysiology of AF. (Gersh et al.
Patterns of atrial fibrillation (AF ) First detected Paroxysmal ( self-terminating ) Persistent ( Not self-terminating ) Episodes that last 7 days or less Cardioversion failed Permanent Episodes that last longer than 7 days ACC / AHA / ESC Guideline 2006 .
Management of AF To suppress To suppress dysrhythmia dysrhythmia • Ventricular • Ventricular rate control rate control • Restorations • Restorations and and maintenance maintenance sinus rhythm sinus rhythm Prevention of Prevention of thromboembolis thromboembolis m m To remove To remove precipitating precipitating factors and factors and optimal optimal treatment of treatment of underlying underlying disease disease ACC / AHA / ESC Guideline 2006 .
Thrombus Forms in the Atria and Embolizes to the Brain .
Red Thrombus vs White Thrombus .
Cardiogenic Stroke .
Ischemic Stroke Intrinsic cerebro 20% vascular disease 80% Cardiac sources of embolism and atheromatous pathology in the prox. aorta .
Thrombus Forms in the Atria and Embolizes to the Brain Courtesy of Dr. Joseph Blackshear .
0001 Two Year age-adjusted incidence of stroke / 100 6 5 4 3 2 1 0 No AF AF Wolf et al. 1991.AF Increases Stroke Risk by Nearly 5x Risk ratio =4.22:983-988 .8 P < 0. Stroke.
3%) AF. In lone AF stroke risk is 0. .5% The annualized rate of ischemic stroke during aspirin treatment was similar in those with paroxysmal (3.Ischemic Stroke Risk The annual risk of ischemic stroke in AF is estimated to be 5-7%. Those with prior stroke or TIA have a rate of subsequent stroke of 10% to 12% per year when treated with aspirin.2%) and permanent (3.
• Age • Prior stroke / TIA • Risk Factors • Underlying Heart Disease • Age • Intensity of anticoagulation • Underlying Clinical Disorder Thrombotic Risk Hemorrhagic Risk The Benefit and Risk of Warfarin Treatment .
Adjusted-Dose Warfarin Compared with Placebo Relative Risk Reduction (95% CI) AFASAK I SPAF BAATAF CAFA SPINAF EAFT All Trials (n=5) 100% 50% Warfarin Better 0 –50% -100% Warfarin Worse Antithrombotic therapy for prevention of stroke (ischemic and hemorrhagic) in patients with nonvalvular AF: adjusted-dose warfarin compared with placebo (Fuster et al. 2001) .
Efficacy of Aspirin in AF No. of PatientEvents years Risk Reduction (%) AFASAK SPAF 35 65 807 1457 838 EAFT 130 Combined*230 3102 100 50 0 -50 Aspirin Better Aspirin Worse *Total risk reduction for all 3 studies combined is -1 .
Warfarin compared with Aspirin in AF Relative Risk Reduction ( 95% CI ) AFASAK I( 432 ) AFASAK II EAFT PATAF SPAF II ( 439 ) ( 403 ) ( 443 ) ( 440 ) All Trials ( n = 5 ) 100% 50% 0 -50% -100% Risk reduction ( combined ) is 31% Warfarin better Warfarin worse ( 95% CI 13% to 49% ) ACC / AHA / ESC Guideline 2006 .
1999) .analysis of antithrombotic therapy to prevent stroke in atrial fibrillation (Hart et all.62 60 Warfarin Aspirin Risk Reduction %/year 50 40 20 10 22 Warfarin Aspirin A meta.
7 x 1.6 x Increasing age (per decade) ACC / AHA / ESC Guideline 2006 .Predicting Stroke Risk in AF: Multivariate Analysis of Pooled Data Clinical risk factors Previous stroke or TIA Diabetes Relative risk 2.5 x 1.4 x History of hypertension 1.
0 2.0 4.0 5.0 7.0 3.0 6.. Oden et all.0 International Normalized Ratio Adjusted odds ratios for ischemic stroke and intracranial bleeding in relation to intensity of anticoagulation. 2006) .20 15 Ischemic Stroke Intracranial bleeding Odds ratio 10 5 1 1. (Hylek & Singer.0 8. 1994.
2 %/y 1 0 AFASAK SPAF BAATAF CAFA SPINAF Patients with nonvalvular atrial fibrillation Mean age was 69 years Major hemorrhage : .Annual rates of major hemorrhage during anticoagulant 5 Major bleeding rate ( %/y ) 4 3 2 Average = 1.require hospitalization .require transfusion or surgical .permanently disabling or fatal ACC / AHA / ESC Guideline 2006 .
target 2.5.0 to 3. 81 to 325 mg daily Low-risk patients (approximately < 2 major thrombo-embolic events / 100 patients/year) Female gender Age 65-74 years Coronary artery disease Thyrotoxicosis a If mechanical valve. 81 to 325 mg daily.5)a thrombo-embolic events/100 patients/year) Previous stroke. target major thrombo-embolic events/100 patients / 2.0.Antithrombotic therapy for patients with atrial fibrillation Risk category Recommended therapy High-risk patients (approximately > 6 major Warfarin (INR 2. or Intermediate-risk patients (approximately 2 – 6 warfarin (INR 2. TIA or systemic embolism Mitral stenosis Prosthetic heart value Aspirin.0. (Fuster et al. target international normalized ratio (INR) greater than 2..0 to 3. 2006) .5) year) Age > 75 years Hypertension Heart failure Left ventricular ejection fraction < 35% Diabetes mellitus Aspirin.
warfarin reduces the risk of stroke by 45% and cardiovascular event by 29%. The absolute rate increase of major bleeding with warfarin is 1.2 events per 100 patient-years Around 50 % of AF patients with additional stroke risk factors and without contraindication do not receive warfarin. Compared with aspirin.Warfarin Therapy Warfarin reduces strokes by 62% compared with no treatment. .
Number Needed to Treat • Warfarin Primary prevention : 1 stroke over 37 patients per year Secondary prevention : 1 stroke over 12 patients per year • Aspirin Primary prevention : 1 stroke over 67 patients per year Secondary prevention : 1 stroke over 40 patients per year .
0 2419 2466 1.02 0.04 RR=1.5 3168 3232 Years 1.03 0.p-0.05 0.72 (1.5 941 930 Cumulative risk of stroke .37).24-2.The ACTIVE W Trial 0.01 0 Oral anticoagulation therapy Clopidogrel + aspirin 0 Number at risk Clopidogrel 3335 * Aspirin Oral anticoagulation therapy 3371 0.001 Cumulative hazard rates 0.
Verification of the patient’s comprehension of the disease and its treatment. 2005) .The treatment of anticoagulation should still be made on an individual basis after the following : Appropriate stratification of their thromboembolic and hemorrhagic risk. Assessment of their ability to manage their own health care and to comply with therapy and in conjunction with their treatment preferences (Poli et all.
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