1. The Management of AF Warfarin New anticoagulants 16 Sept 2011

2. Efficacy of Warfarin AFASAK27811 BAATAF15922 CAFA14478 SPAF23508 SPINAF29972 Combined*1083691 No. of EventsPatient-years 100 50 0 -50 -100 Warfarin Better Warfarin Worse Risk Reduction, % *Total risk reduction for all 5 studies combined is 68% studies combined is 68%

3. Patients Assigned to Warfarin in AF Trials Intensity of Anticoagulation When Stroke Occurred AFASAK SPAF I BAATAFSPINAFCAFA 1.0 2.0 3.0 4.0 1.7 1.6 1.5 1.4 1.3 1.2 1.1 1.0 INR Ratio PT Ratio (ISI 2.4) INR: 2.0–3.0 1.8 Target range for individual study

4. Dr Maneesh Bhargava Dr Arindam Kar Dr Richard Perry Dr Diane Ames St Mary’s Hospital Imperial College NHS Trust UK Anticoagulation is underused and suboptimal in high risk patients with atrial fibrillation who present with a stroke - 5 year data

5. St Mary’s data - Stroke with AF and no contra-indication to anti-coaguation

6. Prediction of Annual Stroke Risk - CHADS2 Gage et al, JAMA 2001 C Recent CHF H Hypertension A Age > 75 yrs D Diabetes S 2 History of CVA or TIA

7. CHA 2 DS 2 -VASc

8. CHADS 0 and 1 Olesen et al BMJ 2011; 342:d124

9. CHADSVASc 0 and 1 Olesen et al BMJ 2011; 342:d124

11. Thursday, March 31, 2011 Improving the Management of Atrial Fibrillation: Ambassadors Hotel, London CHART Online Data uploads PCTs77 Practices868 Population covered6 million Patients with AF108,662 High risk patients61,226

12. Thursday, March 31, 2011 Improving the Management of Atrial Fibrillation: Ambassadors Hotel, London May 16 2011

13. AF prevalence V % patients age > 65 by Network

16. Achieving reasonable conversion rates after running GRASP is a major problem

17. Thursday, March 31, 2011 Improving the Management of Atrial Fibrillation: Ambassadors Hotel, London May 16, 2011

18. Contra-indications York study Absolute17423% Relative 19626% Patient declined 9312% Doctor’s decision26134% Not coded 43 5% K Griffith A Graham

19. Treatment by age

20. Prevalence of AF amongst stroke patients

21. Attributable risk - % strokes due to AF

22. BAFTA - primary endpoints Primary endpoints –Fatal or non-fatal disabling stroke –Other intracranial haemorrhage –Arterial embolism Warfarin 1.8 % / year Aspirin 3.8 % / year Relative risk 0.48 (95 % CI 0.28 – 0.8)

24. CHADS > 1 45.4%

25. CHADS > 1 77.7%

26. Warfarin substitutes

27. RE-LY Study Stroke or Systemic embolism NEJM, Sept 2009

28. Apixaban – stroke / systemic embolism

29. Time in therapeutic range RELY Dabigatran64 % ARISTOTLEApixaban62 % ROCKET Rivaroxaban55 %

31. RELY - Mean time in therapeutic range by country

33. ARISTOTLE TTR by country

34. Aristotle – benefit by quartile of TTR

35. £ 2800£ 5165 £ 29365Warfarin superior Overall cost / QALY £ 12640

36. NHS- I Commissioning guide

37. Influence of Time in therapeutic range What would an improvement of 5 % achieve? An approximate improvement in odds ratio of 0.23 Equivalent to NNT of 434 245,655 patients nationally on warfarin (NICE) Would prevent 565 strokes “Free”

38. Time in therapeutic range 2.0 - 3.0 UK anti-coagulant clinics

39. Why does TTR vary between clinics? ? Differences between patients –Age –Co-morbidities –Other drug therapy –Alcohol –Indication for anti-coagulation ? Differences in service delivery –Patient allocation between primary and secondary care Differences in clinical supervision

40. Conclusions Warfarin is an amazingly effective drug There is still great reluctance to use it We can combat this reluctance: –Education –Change in QOF (hopefully) We need to focus on quality of anti-coagulation –Improving TTR with warfarin –Appropriate use of the newer drugs