1. Prevention of thromboembolism in AF ACC/AHA/ESC Guidelines Jin-Bae Kim, MD, PhD Arrhythmia Service, Division of Cardiology Cardiovascular Center, Kyung Hee Univ Hospital

2. Atrial Fibrillation (AF ) : 1. A supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. 2. On ECG, AF is described by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in size, shape, and timing, associated with an irregular, frequently rapid ventricular response when AV conduction is intact. DEFINITION :

3. Classification: Paroxysmal AF: patient has had 2 or more episodes ( recurrent AF ) and the arrhythmia terminates spontaneously. Persistent AF: recurrent AF with sustained arrhythmia Permanent AF: long-standing AF ( e.g. greater than 1 year) in which cardioversion had not been indicated or attempted.

4. Patterns of atrial fibrillation First detected 1. Paroxysmal (Self-terminating) 2. Persistent (Not self-terminating) 3. Permanent 1. less than 7d (most ≤ 24hrs) 2. more than 7d CASE III-16-4

5. 1. Maintenance of sinus rhythm 2. Control of rapid ventricular rate 3. Prevention of thromboembolism Therapeutic Goals CASE III-16-6

6. Thromboembolic Events Control Patients in AF Trials Cerebral 49 (91%) Systemic 5 (9%)

7. Thromboembolic Events - Mechanism Thrombus formation begins with Virchow’s triad of stasis, endothelial dysfunction, and a hypercoagulable state. Stunning of the LAA seems responsible for an increased risk of thromboembolic events after successful cardioversion, regardless of whether the method is electrical, pharmacological, or spontaneous. Decreased flow within the LA/LAA during AF has been associated with spontaneous echo contrast (SEC), thrombusformation, and embolic events.

8. Thromboembolic Events - Mechanism This phenomenon relates to fibrinogen-mediated erythrocyte aggregation and is not resolved by anticoagulation. Because the pathophysiology of thromboembolism in patients with AF is uncertain, the mechanisms linking risk factors to ischemic stroke in patients with AF are incompletely defined.

9. AFFIRM Stroke Events 5.5 7.1 1.1 1.3 0.80.8 7.4 8.9 P=.79 P=.73 P=.68 P=.93 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. Percent 0 1 2 3 4 5 6 7 8 9 Ischemic stroke ICHSDH/SAHAll stroke RateRhythm

10. Less Validated or Weaker Risk Factors Moderate-Risk Factors High-Risk Factors Female genderAge ≥ 75 yPrevious stroke, TIA or embolism Age 65 to 74 yHypertensionMitral stenosis Coronary artery disease Heart FailureProsthetic heart valve ThyrotoxicosisLVEF ≤ 35% Diabetes mellitus Classification of Stroke Risk Factors Fuster V. et.al. JACC 2006

11. Antithrombotic therapy for patients with atrial fibrillation Risk CategoryRecommended Therapy No risk factorsAspirin, 81 to 325 mg daily One moderate-risk factorAspirin, 81 to 325 mg daily, or Warfarin (INR 2.0 to 3.0, target 2.5) Any high-risk factor or ≥ 2 moderate risk factor Warfarin (INR 2.0 to 3.0, target 2.5) Fuster V. et.al. JACC 2006

12. CHA 2 DS 2 VASc score and stroke rate Risk factors ≥ 75 yrs old(2) Previous stroke, TIA Thromboemolism(2) CHF(1) HT(1) DM(1) Vascular disease(1) 65~74 세 (1) Female(1) Adjusted stroke rate according to CHA 2 DS 2 VASc score CHA 2 DS 2 VASc score Patients(n=7329) Adjusted stroke rate(%/year) 010% 14221.3% 212302.2% 317303.2% 417184.0% 511596.7% 66799.8% 72949.6% 8826.7% 91415.2% Camm AJ, et al. Eur Heart J 2010

13. ACTIVE A and W: Stroke Rates and Risk Reductions TreatmentVKAC+AAspirin ACTIVE W (Rate per year) 1.42.4-- ACTIVE A (Rate per year) --2.43.3 RRR versus Aspirin-58%-28%-- RRR versus C+A -42% --

14. International Normalized Ratio Odén A, et. al. Thromb Res 2006 20 15 10 5 1 1.02.03.04.05.06.07.08.0 Ischemic Stroke Intracranial bleeding

15. Doubling of the rate of intracranial hemorrhage when the INR exceeds 3.0 70% increases in the rate of stroke when the INR is less than 2.0

16. HAS-BLED bleeding risk score bleeding risk score Elderly > 65yrs old(1) Stroke(1) Hypertension(1) Abnormal renal function(1) Abnormal liver function(1) Vascular disease(1) Bleeding(1) Labile INRs(1) Drugs(1) Alcohol(1) LetterClinical characteristic a Points awarded HHypertension1 A Abnormal renal and liver Function(1 point each) 1 or 2 SStroke1 BBleeding1 LLabile INRs1 EElderly(e.g.age>65years)1 D Drugs or alcohol(1 point each) 1 or 2 Maximum 9 points Pisters R, at al, Chest 2010