Stratifying stroke risk to guide antithrombotic therapy in patients with AF

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

2. No evidence that AF type significantly impacts stroke risk Incidence of a first ischaemic stroke *In paroxysmal versus permanent AF in subjects without prior stroke Friberget al,Eur Heart J 2010 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

3. Stroke Risk in AF Working Group: factors influencing stroke risk in patients with AF Pooled analysis of seven randomized trials1 *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. Cammet al, Eur Heart J 2010

4. Different schemes designed to stratify stroke risk in patients with AF 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 Walravenet al, Arch Intern Med 2003; 10. Fusteret al, Circulation 2006; 11. Lip et al, Chest 2010 Atrial Fibrillation Investigators (1994)1 Stroke Prevention in AtrialFibrillation (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

5. Differences in risk stratification schemes yield varying degrees of stroke risk 100 Low Moderate 80 High 60 Patients (%) 40 20 0 AFI SPAF ACCP2001 ACCP2004 CHADS2 Fram. vanWalraven 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 Baruch et al, Stroke 2007

6. CHADS2 is the most recognized risk stratification scheme Add points together *Per 100 patient-years without antithrombotic therapy Gage et al, JAMA 2001 1 or 2 points are assigned as shown for each of the risk factors below Stroke risk is determined by the cumulative score

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 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 *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 Cammet al, Eur Heart J 2010

10. Many stroke risk factors are also risk factors for bleeding *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 Higher stroke risk = higher bleeding risk

11. 1-year risk of major bleeding increases with HAS-BLED score AF cohort of the Euro Heart Survey P value for trend = 0.007 HAS-BLED score Pisterset al, Chest 2010

12. ATRIA: a risk scheme to predict warfarin-associated haemorrhage *Defined as estimated glomerular filtration rate <30 ml/min or dialysis-dependent Fang et al, J Am Coll Cardiol 2011