ATRIAL FIBRILLATION 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
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ATRIAL FIBRILLATION
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
The Probability of Developing AF Increases With Age
0
2
4
6
8
10
12
<55 55-59 60-64 65-69 70-74 75-79 80-84 >85
Women MenGo et al. JAMA. 2001;285:2370-2375
Pre
vale
nce (
% )
Leading Circle Reentry Ectopic Foci
Right Atrium Left Atrium1 2
34
5
6
130
110190
110
130 50
10
50
30
30
1 2
34
5
6
230
230 250
250 210
210150
170
170
190
SuperiorVenaCava
InferiorVenaCava
FossaOvails
Septum
PulmonaryVeins
CoronarySinus n = 45 pts
116
1731
The Mechanisms Underlying Human AF
Hypothetical construct of the pathophysiology of AF.
Pathophysiology of Atrial Fibrillation
? Inflammation
• compliance• Mitral stenosis / regurgitation
• LVH• Diastolic
dysfunction
stretch-activated channels dispersion of refractoriness pulmonary vein focal/discharges?
Increased vulnerability to atrial pathophysiology of AF
? Inflammation
Atrial dilatation/stretch
(Gersh et al, 2004)
PermanentPermanent
Paroxysmal( self-terminating )
Paroxysmal( self-terminating )
Persistent( Not self-terminating )
Persistent( Not self-terminating )
First detectedFirst detected
Patterns of atrial fibrillation (AF )
Episodes that last 7 days or less
Episodes that last longer than 7 days
Cardioversion failedACC / AHA / ESC Guideline 2006
Management of AFManagement of AF
To suppress dysrhythmia
• Ventricular rate control
•Restorations and maintenance sinus rhythm
To suppress dysrhythmia
• Ventricular rate control
•Restorations and maintenance sinus rhythm
Prevention of thromboembolis
m
Prevention of thromboembolis
m
To remove precipitating factors and
optimal treatment of underlying
disease
To remove precipitating factors and
optimal treatment of underlying
disease
ACC / AHA / ESC Guideline 2006
Thrombus Forms in the Atria and Embolizes to the Brain
Red Thrombus vs White Thrombus
Cardiogenic Stroke
80%
20%
80%
20%
Intrinsic cerebro vascular disease
Cardiac sources of embolism and atheromatous pathology in the prox. aorta
Ischemic Stroke
Thrombus Forms in the Atria and Embolizes to the Brain
Courtesy of Dr. Joseph Blackshear
0
1
2
3
4
5
6
No AF AF
Risk ratio =4,8P < 0,0001
Tw
o Y
ear
ag
e-a
dju
sted inci
dence
of
stro
ke /
100
AF Increases Stroke Risk by Nearly 5x
Wolf et al. Stroke. 1991;22:983-988
Ischemic Stroke Risk
The annual risk of ischemic stroke in AF is estimated to be 5-7%.
In lone AF stroke risk is 0.5%The annualized rate of ischemic stroke
during aspirin treatment was similar in those with paroxysmal (3.2%) and permanent (3.3%) AF.
Those with prior stroke or TIA have a rate of subsequent stroke of 10% to 12% per year when treated with aspirin.
Thrombotic Risk Hemorrhagic Risk
• Age• Prior stroke / TIA• Risk Factors• Underlying Heart Disease
• Age • Intensity of anticoagulation• Underlying Clinical Disorder
The Benefit and Risk of Warfarin Treatment The Benefit and Risk of Warfarin Treatment
Antithrombotic therapy for prevention of stroke (ischemic and hemorrhagic) in patients with nonvalvular AF: adjusted-dose warfarin compared with placebo
Adjusted-Dose Warfarin Compared with Placebo
Relative Risk Reduction(95% CI)
AFASAK I
SPAF
BAATAF
CAFA
SPINAF
EAFT
All Trials (n=5)
Warfarin Better Warfarin Worse
100% 50% 0 –50% -100%
(Fuster et al, 2001)
Efficacy of Aspirin in AF
AFASAK 35 807
SPAF 65 1457
EAFT 130 838
Combined* 230 3102
No. ofEvents
Patient-years
100 50 0 -50 -100
Aspirin Better Aspirin Worse
Risk Reduction (%)
*Total risk reduction for all 3 studies combined is 21%
AFASAK I ( 432 )
AFASAK II ( 439 )
EAFT ( 403 )
PATAF ( 443 )
SPAF II ( 440 )
All Trials ( n = 5 )
Relative Risk Reduction( 95% CI )
100% 50% 0 -50% -100%
Warfarin better Warfarin worse
Warfarin compared with Aspirin in AF
Risk reduction ( combined ) is 31% ( 95% CI 13% to 49% )
ACC / AHA / ESC Guideline 2006
60
50
40
20
10
A meta- analysis of antithrombotic therapy to prevent stroke in atrial fibrillation
(Hart et all, 1999)
Warfarin
Aspirin
Ris
k R
educ
tion
%/y
ear
62
22
Warfarin Aspirin
Predicting Stroke Risk in AF:Multivariate Analysis of Pooled Data
Clinical risk factors Relative risk
Previous stroke or TIA 2.5 x
History of hypertension 1.6 x
Diabetes 1.7 x
Increasing age (per decade) 1.4 x
ACC / AHA / ESC Guideline 2006
Adjusted odds ratios for ischemic stroke and intracranial bleeding in relation to intensity of anticoagulation.
(Hylek & Singer, 1994; Oden et all., 2006)
International Normalized Ratio
1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0
20
15
10
5
1
Ischemic Stroke
Intracranial bleeding
Odd
s ra
tio
5
4
3
2
1
0AFASAK SPAF BAATAF CAFA SPINAF
Major bleeding rate ( %/y )
Average = 1,2 %/y
Annual rates of major hemorrhage during anticoagulant
Patients with nonvalvular atrial fibrillationMean age was 69 yearsMajor hemorrhage : - require hospitalization
- require transfusion or surgical - permanently disabling or fatal
ACC / AHA / ESC Guideline 2006
Antithrombotic therapy for patients with atrial fibrillation
Risk category Recommended therapy
High-risk patients (approximately > 6 major thrombo-embolic events/100 patients/year)
Previous stroke, TIA or systemic embolism Mitral stenosis Prosthetic heart valueIntermediate-risk patients (approximately 2 –
6 major thrombo-embolic events/100 patients / year)
Age > 75 years Hypertension Heart failure Left ventricular ejection fraction < 35% Diabetes mellitusLow-risk patients (approximately < 2 major
thrombo-embolic events / 100 patients/year) Female gender Age 65-74 years Coronary artery disease Thyrotoxicosis
Warfarin (INR 2.0 to 3.0, target 2.5)a
Aspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5)
Aspirin, 81 to 325 mg daily
(Fuster et al., 2006)
aIf mechanical valve, target international normalized ratio (INR) greater than 2,5.
Warfarin Therapy
Warfarin reduces strokes by 62% compared with no treatment.
Compared with 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.
Number Needed to Treat
• WarfarinPrimary prevention :
1 stroke over 37 patients per yearSecondary 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
Cumulative risk of stroke
Number at riskClopidogrel* Aspirin
Oralanticoagulationtherapy
3335 3168 2419 941
3371 3232 2466 930
Years0 0.5 1.0 1.5
0.05
0.04
0.03
0.02
0.01
0
Cum
ula
tive
ha
zard
rat
es
Oral anticoagulation therapy
Clopidogrel + aspirin
RR=1.72 (1.24-2.37).p-0.001
The ACTIVE W Trial
The treatment of anticoagulation should still be made on an individual basis after the following :
Appropriate stratification of their
thromboembolic and hemorrhagic risk.
Verification of the patient’s comprehension of
the disease and its treatment.
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, 2005)
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