1. BS Evidence Based Medicine And Atrial Fibrillation

2. BS Go et al; JAMA; 2001 Age and Prevalence of AF Atria Study 1.9 million pts in HMO 17,974 pts with AF 45% > 75 years

3. BS Age and Projected Prevalence of AF Atria Study Go et al; JAMA; 2001

4. BS Atrial Fibrillation In The Elderly Are Older Patients Different? Younger Patients Elderly Patients Associated Disease +/-+++ Symptoms++++ Intermittent/Chronic I > C C > I Thromboembolic Risk ++++ Hemorrhagic Risk +/-++

5. BS Evidence based medicine l 80 year old male l Hypertension for 5 years; Atrial fib ? duration l Treated with diuretic and ACE: BP 150/87 mmHg l Electrocardiograph – within normal limits l Echocardiogram – EF 50% early diastolic relaxation abnormality l Creatinine 99 umol / l

6. BS Atrial Fibrillation In The Elderly Thromboembolism l 5 year stroke risk is 15% Aspirin  risk by 20%; ARR 0.6; NNT 166 Aspirin  risk by 20%; ARR 0.6; NNT 166 Warfarin risk  x 70%; ARR 2.1: NNT 47.6 Warfarin risk  x 70%; ARR 2.1: NNT 47.6 l Aspirin major risk 1% pa; warfarin 3% pa l P warfarin benefit 100 – (85) + 4.5 = 10.5% l P Aspirin benefit 100 – (85) + 12 = 3%

7. BS Computer Decision support

8. BS

16. Comparison of Decision Model for patients > 75 only with clinical practice Current treatment N (%) Recommended WarfarinAntiplateletNil Both Placebo 5 (38.5)8 (61.5)00 Warfarin 11 (52.4)7 (33.3)3 (14.3)0 Aspirin 46 (48.4)41 (43.2)7 (7.4)1 (1.0) Proportion where current treatment = recommended treatment is 41.1% (53/129) 10% (13/129) on some medication when none recommended

17. BS Evidence based medicine l Decision support can provide evidence based information to assist in clinical decision making l Clinicians believe that their decisions on OAC for atrial fibrillation are evidence based ? l However a computer decision support program did not agree that the majority of therapeutic decisions were likely to advantage the patient

18. BS Evidence based medicine Risk benefit ? l l Balancing the risks of stroke and upper GI tract bleeding in older patients with atrial fibrillation. Arch Intern Med 2002: 162(5) ; 541 - 50 l l For 65-yr with average risks of stroke and upper GI tract bleeding, warfarin 12.0; aspirin 10.8 and no antithrombotic Rx, 10.1 QALYs per patient l l For 80yr, baseline stroke risk 4.3% pa, warfarin, 7.44; aspirin, 7.39; and no treatment, 7.21 QALYs per patient

19. BS Evidence based medicine l 80 year old male l Hypertension for 5 years; Atrial fib ? duration l Treated with diuretic and ACE: BP 150/87 mmHg l Electrocardiograph – within normal limits l Echocardiogram – EF 50% early diastolic relaxation abnormality l Creatinine 99 umol / l

20. BS

23. Am Heart J. 2005; 149 (4): 650-656. Calculation of Risk-Benefit Ratio

24. BS Evidence based medicine

25. BS Evidence based medicine l Warfarin reduces the risk of stroke by about two-thirds compared with placebo (ARR, 3.1% per year; NNT, 32) and by about a third compared with aspirin (ARR, 0.8% per year; NNT, 125), but causes at least twice as many intra- cranial and extra-cranial bleeds as aspirin

26. BS Evidence based medicine

27. Calculation of Risk-Benefit Ratio l Predicted event rate in population from calculator l Multiply by RRR (Relative risk reduction) l Gives the ARR (Absolute Risk Reduction) l 1 / ARR = NNT (Patient yr to prevent stroke) l NNH (numbers to harm) l 1 / Serious ADR

28. Calculation of Risk-Benefit Ratio l Warfarin ( NNT – 32 : NNH – 80) l ARR = 100 / 30 = 3.13% l Assumed stroke risk – 3.13 / 0.7 = 4.46% l Bleed assumed rate 100 / 80 = 1.25% l Assuming risk rate unrelated to warfarin 0.8% l Total bleed rate 2.1%

29. Calculation of Risk-Benefit Ratio l 80 yr old male, unCx Atrial fibrillation, BP 150/87 l Stroke risk – Framingham 5yr (8 points) – 11% l Stroke risk – CHADS2 (4% pa) – 20% l Bleeding risk – AFFIRM (2% pa + age 1.05) – 10.1% l Stroke risk is 3% and bleed risk 2%

30. Calculation of Risk-Benefit Ratio l 80 yr old male, unCx Atrial fibrillation, BP 150/87 l Stroke risk – on Warfarin (3 – (0.7 * 3)) = 0.9 l Absolute risk reduction = 2.1 (NNT 47.6) l Bleeding risk = 2% pa (NNH 83) l Applying principle of risk equivalence – l ADR / Relative risk benefit (1.2 / 0.7 = 1.7) l Risk must > 1.7 for a favourable risk profile

31. BS Evidence based medicine Risk benefit ? l HEMORR 2 HAGES National Register of Atr Fibrillation l l Anti-thrombotic Rx on individual risks and benefits l l Hospitalization for bleed / warfarin was 4.9 per 100 patient-yr, but depended on comorbidity (NNH 24.2) l l High-risk patients haemorrhage rate (7.5-15.3) much greater than the low-risk patients (1.1-2.9) l l Previous trial estimates - 2.4 per 100 yr (NNH 62.5)

32. Am Heart J. 2006;151(3):713-719. Evidence based medicine Harm (NNH) 90.9 58.8 22.2 13.2 10.4 8.7 24.4

33. Calculation of Risk-Benefit Ratio l 80 yr old male, unCx Atrial fibrillation, BP 150/87 l Stroke risk – on Warfarin (3 – (0.7 * 3)) = 0.9 l Absolute risk reduction = 2.1 (NNT 47.6) l Bleeding risk = 4.9% pa (NNH 24.4) l Applying principle of risk equivalence – l ADR / Relative risk benefit (4.1 / 0.7 = 5.9) l Risk must > 5.9 for a favourable risk profile

34. BS

35. Evidence based medicine High risk and warfarin? l CHAD2 SCORE > 3 - a stroke risk of 9 % l Stroke risk – on Warfarin (9 – (0.7 * 9)) = 2.7 l Absolute risk reduction = 6.3 (NNT 15.9) l The major bleed risk is 4.9% pa (NNH 20.4) l Risk equivalence (4.1 / 0.7) – stroke rate of 5.9% l Warfarin no difference 68.5% - ((100 – 45) + 13.5))

36. BS Evidence based medicine Is aspirin a rational choice ? l Aged 80 yr (atrial fib) has a 5 yr stroke risk of 15% l Aspirin will reduce that risk by 20% l No event in 85% + 12 events not prevented l Aspirin will make no difference 97% of the time l Absolute risk reduction (ARR) – 0.6 (NNT 166.6) l The average bleed risk is 0.2% x 5 = 1%

37. BS Evidence based medicine Patient preferences ? l Malcolm Man-Son-Hing, et al, Medical Decision Making 2005: 25; 548-559 (Systemic review n = 8) l Fewer patients opt for warfarin compared with guidelines ( 5 / 8 studies) l Aspirin stroke rate of 1 %, opt for warfarin 50% l Aspirin stroke rate 2%,opt for warfarin 66% l Aspirin stroke rate 2 – 6% in 3 to choose warfarin l Physicians balance patient preferences with Rx recommendations of clinical practice guidelines

38. BS Evidence based medicine Anyone who believes that the same thing can be suited to everyone is a great fool, since medicine is practiced not on mankind in general but on every individual in particular Henry De Mondeville circa 1300

39. BS