1. Stratifying stroke risk to guide antithrombotic therapy in patients with AF

2. No evidence that AF type significantly impacts stroke risk
Scandinavian follow-up study of patients treated for paroxysmal (n=855) and permanent AF (n=1126) during 2002 (mean follow-up 3.6 years)
Aim: to investigate differences in stroke risk in the two cohorts
Incidence of a first ischaemic stroke
Paroxysmal AF
Permanent AF
p-value
Multivariable-adjusted hazard ratio for ischaemic stroke (95% CI)*
Events/ 1000 patient-yr
Events/ 1000 patient-yr 21 25
0.45
1.07 (0.71–1.61)
Reference: Friberg et al. Eur Heart J 2010;31:967–975
*In paroxysmal versus permanent AF in subjects without prior stroke
Friberg et al, Eur Heart J 2010

3. Stroke Risk in AF Working Group: factors influencing stroke risk in patients with AF
Pooled analysis of seven randomized trials1
Risk factor
Adjusted RR (95% CI)
Prior stroke/TIA
2.5 (1.8–3.5)
Increasing age
1.5/decade (1.3–1.7)
History of hypertension
2.0 (1.6–2.5)
Diabetes mellitus
1.7 (1.4–2.0)
Female gender
1.6–1.9*
Heart failure
Inconclusive#
Coronary artery disease
Inconclusive
References; Stroke Risk in Atrial Fibrillation Working Group. Neurology 2007;69:546−554, Camm et al. Eur Heart J 2010;31:2369–2429
*Only a range of adjusted RRs reported for female gender
#While studies show a clear risk of thromboembolism with moderate to severe systolic impairment, the risk of thromboembolism with heart failure and preserved ejection fraction is less defined2
1. Stroke Risk in Atrial Fibrillation Working Group, Neurology 2007; 2. Camm et al, Eur Heart J 2010 3

4. Different schemes designed to stratify stroke risk in patients with AF
Atrial Fibrillation Investigators (1994)1
Stroke Prevention in Atrial Fibrillation (SPAF, 1999)2
CHADS2 (2001 and 2004)3,4
American College of Chest Physicians (ACCP) guidelines (2001, 2004 and 2008)5–7
Framingham (2003)8
van Walraven (2003)9
ACC/AHA/ESC guidelines (2006)10
CHA2DS2-VASc (2010)11
References: Atrial Fibrillation Investigators. Arch Intern Med 1994;154:1449–1457, Hart et al. Stroke 1999;30:1223–1229, Gage et al. JAMA 2001;285:2864–2870, Gage et al. Circulation 2004;110:2287–2292, Albers et al.Chest 2001;119:194S–206S, Singer et al. Chest 2004;126:429S–456S, Singer et al. Chest 2008;133:546S–592S, Wang et al. JAMA 2003;290:1049–1056, van Walraven et al. Arch Intern Med 2003;163:936–943, Fuster et al. Circulation 2006;114:e257– e354, Lip et al. Chest 2010;137:263–272
1. AFI, Arch Intern Med 1994; 2. Hart et al, Stroke 1999; 3. Gage et al, JAMA 2001; 4. Gage et al, Circulation 2004; 5. Albers et al, Chest 2001; 6. Singer et al, Chest 2004; 7. Singer et al, Chest 2008; 8. Wang et al, JAMA 2003; 9. van Walraven et al, Arch Intern Med 2003; 10. Fuster et al, Circulation 2006; 11. Lip et al, Chest 2010

5. Differences in risk stratification schemes yield varying degrees of stroke risk
Percentage of patients with AF (enrolled in the SPORTIF III and V trials) classified as being at low, moderate and high risk of stroke, according to individual risk stratification schemes
100
Low
Moderate 80
High 60
Patients (%) 40
Reference: Baruch et al. Stroke 2007;38:2459–2463 20
AFI
SPAF
ACCP 2001
ACCP 2004
CHADS2
Fram.
van Walraven
Baruch et al, Stroke 2007

6. CHADS2 is the most recognized risk stratification scheme
1 or 2 points are assigned as shown for each of the risk factors below
Stroke risk is determined by the cumulative score
Item
Points
Congestive heart failure 1
Hypertension
Age ≥75 years
Diabetes mellitus
Stroke/TIA 2
CHADS2 6 5 4 3 2 1
Stroke rate (95% CI)*
18.2 (10.5–27.4)
12.5 (8.2–17.5)
8.5 (6.3–11.1)
5.9 (4.6–7.3)
4.0 (3.1–5.1)
2.8 (2.0–3.8)
1.9 (1.2–3.0)
Add points together
Reference; Gage et al. JAMA 2001;285:2864–2870
*Per 100 patient-years without antithrombotic therapy
Gage et al, JAMA 2001 6

7. ACCF/AHA/HRS 2011 and ACCP 2008 guidelines: based on CHADS2
CHADS2 scoring1
CHF +1
Hypertension +1
Age ≥75 years +1
Diabetes mellitus +1
Prior Stroke or TIA +2
Recommended therapy
CHADS2 score
ACCP 20082
ACCF/AHA/HRS
20113
ASA 75–325 mg/day
ASA 81–325 mg/day 1
VKA (INR 2–3) or ASA 75–325 mg/day
VKA (INR 2–3) or ASA 81–325 mg/day ≥2
VKA (INR 2–3)
References; Gage et al. JAMA 2001;285:2864–2870, Singer et al. Chest 2008;133:546S–592S, Fuster et al. Circulation 2011;123:e269–e367
1. Gage et al, JAMA 2001; 2. Singer et al, Chest 2008; 3. Fuster et al, Circulation 2011

8. CHA2DS2-VASc: a further refinement of CHADS2
Risk factor
Points
Congestive heart failure/LV dysfunction* +1
Hypertension
Age ≥75 years +2
Diabetes mellitus
Previous stroke/TIA/thromboembolism
Vascular disease (MI, aortic plaque, peripheral artery disease)#
Age 65–74 years
Sex category (female)
Maximum score 9
References: Camm et al. Eur Heart J 2010;31:2369–2429, Lip et al. Chest 2010;137:263–272
*Left ventricular ejection fraction ≤40%; #Including prior revascularization, amputation due to peripheral artery disease or angiographic evidence of peripheral artery disease
Camm et al, Eur Heart J 2010; Lip et al, Chest 2010

9. ESC 2010 guidelines: based on CHADS2 and CHA2DS2-VASc
CHF/LV dysfunction +1
Hypertension +1
Age ≥75 years +2
Diabetes mellitus +1
Prior Stroke/TIA/TE +2
Vascular disease +1
Age 65–74 years +1
Sex category (female) +1
Initial evaluation: CHADS2
If CHADS2 ≥2  oral anticoagulation
If CHADS2 <2  CHA2DS2-VASc
Risk category
CHA2DS2-VASc score
Antithrombotic therapy
No risk factors
ASA 75–325 mg/day or nothing (preferably nothing)
One ‘clinically relevant
non-major’ risk factor 1
Oral anticoagulation (INR 2–3) or ASA 75–325 mg/day (preferably oral anticoagulant)
One ‘major’ risk factor or ≥2 ‘clinically relevant non-major’
risk factors ≥2
Oral anticoagulation (INR 2–3)
Reference: Camm et al. Eur Heart J 2010;31:2369–429
Camm et al, Eur Heart J 2010 9

10. Many stroke risk factors are also risk factors for bleeding
Higher stroke risk = higher bleeding risk
Risk factor for stroke*
Risk factor for anticoagulant-related bleeding*
Advanced age14 
History of hypertension1,3,4
History of MI or ischaemic heart disease1,3
Cerebrovascular disease1–4
Anaemia3,4
Previous history of bleeding3,4
Kidney or liver dysfunction4
Concomitant use of antiplatelets3,4
References: Lip et al. Chest 2010;137:263–272, Hylek et al. Ann Intern Med 1994;120:897–902, Hughes et al. QJM 2007;100:599−607, Pisters et al. Chest 2010;138:1093–1100
*Not exhaustive
The relationship between stroke risk and bleeding risk complicates the evaluation of benefit–risk
1. Lip et al, Chest 2010; 2. Hylek et al, Ann Intern Med 1994; 3. Hughes et al, QJM 2007; 4. Pisters et al, Chest 2010 10

11. 1-year risk of major bleeding increases with HAS-BLED score
AF cohort of the Euro Heart Survey
Clinical characteristic
Points
Hypertension (SBP >160 mm Hg) 1
Abnormal renal or liver function
1 + 1
Stroke
Bleeding
Labile INRs
Elderly (age >65 years)
Drugs or alcohol
Cumulative score
Range 0−9
P value for trend = 0.007
Reference: Pisters et al. Chest 2010;138:1093–110
HAS-BLED score
Pisters et al, Chest 2010 11

12. ATRIA: a risk scheme to predict warfarin-associated haemorrhage
Clinical characteristic
Points
Anaemia 3
Severe renal disease*
Age ≥75 years 2
Any prior haemorrhage diagnosis 1
Diagnosed hypertension
*Defined as estimated glomerular filtration rate <30 ml/min or dialysis-dependent
Low risk
0–3
Intermediate risk 4
High risk
5–10
ATRIA, Anticoagulation and Risk Factors in Atrial Fibrillation, Reference: Fang et al. J Am Coll Cardiol 2011;58:395–401
Fang et al, J Am Coll Cardiol 2011