bs evidence based medicine and atrial fibrillation

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Evidence Based MedicineEvidence Based Medicine

And Atrial FibrillationAnd Atrial Fibrillation

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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

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Age and Projected Prevalence of AF

Atria Study Go et al; JAMA; 2001

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Atrial Fibrillation In The ElderlyAtrial Fibrillation In The ElderlyAre Older Patients Different?Are Older Patients Different?

Younger PatientsYounger Patients Elderly PatientsElderly Patients

Associated DiseaseAssociated Disease +/-+/- ++++++

SymptomsSymptoms ++++++ ++

Intermittent/ChronicIntermittent/Chronic I > CI > C C > IC > I

Thromboembolic RiskThromboembolic Risk ++ ++++++

Hemorrhagic RiskHemorrhagic Risk +/-+/- ++++

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Evidence based medicineEvidence based medicine

80 year old male80 year old male

Hypertension for 5 years; Atrial fib ? durationHypertension for 5 years; Atrial fib ? duration

Treated with diuretic and ACE: BP 150/87 mmHgTreated with diuretic and ACE: BP 150/87 mmHg

Electrocardiograph – within normal limitsElectrocardiograph – within normal limits

Echocardiogram – EF 50% early diastolic Echocardiogram – EF 50% early diastolic

relaxation abnormalityrelaxation abnormality

Creatinine 99 umol / lCreatinine 99 umol / l

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Atrial Fibrillation In The ElderlyAtrial Fibrillation In The ElderlyThromboembolismThromboembolism

5 year stroke risk is 15%5 year stroke risk is 15%

Aspirin Aspirin risk by 20%; ARR 0.6; NNT 166risk by 20%; ARR 0.6; NNT 166

Warfarin risk Warfarin risk x 70%; ARR 2.1: NNT 47.6 x 70%; ARR 2.1: NNT 47.6

Aspirin major risk 1% pa; warfarin 3% pa Aspirin major risk 1% pa; warfarin 3% pa

P warfarin benefit 100 – (85) + 4.5 = 10.5%P warfarin benefit 100 – (85) + 4.5 = 10.5%

P Aspirin benefit 100 – (85) + 12 = 3%P Aspirin benefit 100 – (85) + 12 = 3%

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Computer Decision supportComputer Decision support

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Comparison of Decision Model for patients > 75 only with clinical practice

Current treatment N (%)

Recommended

Warfarin Antiplatelet Nil Both

Placebo 5 (38.5) 8 (61.5) 0 0

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

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Decision support can provide evidence based Decision support can provide evidence based

information to assist in clinical decision makinginformation to assist in clinical decision making

Clinicians believe that their decisions on OAC Clinicians believe that their decisions on OAC

for atrial fibrillation are evidence based ?for atrial fibrillation are evidence based ?

However a computer decision support program However a computer decision support program

did not agree that the majority of therapeutic did not agree that the majority of therapeutic

decisions were likely to advantage the patientdecisions were likely to advantage the patient

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Evidence based medicineEvidence based medicineRisk benefit ?Risk benefit ?

Balancing the risks of stroke and upper GI tract

bleeding in older patients with atrial fibrillation. Arch

Intern Med 2002: 162(5) ; 541 - 50

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

For 80yr, baseline stroke risk 4.3% pa, warfarin, 7.44;

aspirin, 7.39; and no treatment, 7.21 QALYs per

patient

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80 year old male80 year old male

Hypertension for 5 years; Atrial fib ? durationHypertension for 5 years; Atrial fib ? duration

Treated with diuretic and ACE: BP 150/87 mmHgTreated with diuretic and ACE: BP 150/87 mmHg

Electrocardiograph – within normal limitsElectrocardiograph – within normal limits

Echocardiogram – EF 50% early diastolic Echocardiogram – EF 50% early diastolic

relaxation abnormalityrelaxation abnormality

Creatinine 99 umol / lCreatinine 99 umol / l

Am Heart J. 2005; 149 (4): 650-656.

Calculation of Risk-Benefit RatioCalculation of Risk-Benefit Ratio

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Warfarin reduces the risk of stroke by about two-thirds Warfarin reduces the risk of stroke by about two-thirds

compared with placebo (ARR, 3.1% per year; NNT, 32) and compared with placebo (ARR, 3.1% per year; NNT, 32) and

by about a third compared with aspirin (ARR, 0.8% per by about a third compared with aspirin (ARR, 0.8% per

year; NNT, 125), but causes at least twice as many intrayear; NNT, 125), but causes at least twice as many intra--

cranial and extracranial and extra--cranial bleeds as aspirin cranial bleeds as aspirin

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Predicted event rate in population from calculatorPredicted event rate in population from calculator

Multiply by RRR (Relative risk reduction)Multiply by RRR (Relative risk reduction)

Gives the ARR (Absolute Risk Reduction)Gives the ARR (Absolute Risk Reduction)

1 / ARR = NNT (Patient yr to prevent stroke)1 / ARR = NNT (Patient yr to prevent stroke)

NNH (numbers to harm)NNH (numbers to harm)

1 / Serious ADR1 / Serious ADR


Warfarin ( NNT – 32 : NNH – 80)Warfarin ( NNT – 32 : NNH – 80)

ARR = 100 / 30 = 3.13%ARR = 100 / 30 = 3.13%

Assumed stroke risk – 3.13 / 0.7 = 4.46%Assumed stroke risk – 3.13 / 0.7 = 4.46%

Bleed assumed rate 100 / 80 = 1.25%Bleed assumed rate 100 / 80 = 1.25%

Assuming risk rate unrelated to warfarin 0.8%Assuming risk rate unrelated to warfarin 0.8%

Total bleed rate 2.1%Total bleed rate 2.1%


80 yr old male, unCx Atrial fibrillation, BP 150/8780 yr old male, unCx Atrial fibrillation, BP 150/87

Stroke risk – Framingham 5yr (8 points) – 11%Stroke risk – Framingham 5yr (8 points) – 11%

Stroke risk – CHADS2 (4% pa) – 20%Stroke risk – CHADS2 (4% pa) – 20%

Bleeding risk – AFFIRM (2% pa + age 1.05) – 10.1%Bleeding risk – AFFIRM (2% pa + age 1.05) – 10.1%

Stroke risk is 3% and bleed risk 2%Stroke risk is 3% and bleed risk 2%



Stroke risk – on Warfarin (3 – (0.7 * 3)) = 0.9 Stroke risk – on Warfarin (3 – (0.7 * 3)) = 0.9

Absolute risk reduction = 2.1 (NNT 47.6)Absolute risk reduction = 2.1 (NNT 47.6)

Bleeding risk = 2% pa (NNH 83)Bleeding risk = 2% pa (NNH 83)

Applying principle of risk equivalence –Applying principle of risk equivalence –

ADR / Relative risk benefit (1.2 / 0.7 = 1.7)ADR / Relative risk benefit (1.2 / 0.7 = 1.7)

Risk must > 1.7 for a favourable risk profileRisk must > 1.7 for a favourable risk profile

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Evidence based medicineEvidence based medicineRisk benefit ?Risk benefit ?

HEMORRHEMORR22HAGESHAGES National Register of Atr Fibrillation National Register of Atr Fibrillation

Anti-thrombotic Rx on individual risks and benefits

Hospitalization for bleed / warfarin was 4.9 per 100

patient-yr, but depended on comorbidity (NNH 24.2)

High-risk patients haemorrhage rate (7.5-15.3) much

greater than the low-risk patients (1.1-2.9)

Previous trial estimates - 2.4 per 100 yr (NNH 62.5)

Am Heart J. 2006;151(3):713-719.


Harm (NNH)Harm (NNH)

90.990.9

58.858.8

22.222.2

13.213.2

10.410.4

8.78.7

24.424.4



Stroke risk – on Warfarin (3 – (0.7 * 3)) = 0.9 Stroke risk – on Warfarin (3 – (0.7 * 3)) = 0.9


Bleeding risk = 4.9% pa (NNH 24.4)Bleeding risk = 4.9% pa (NNH 24.4)

Applying principle of risk equivalence –Applying principle of risk equivalence –

ADR / Relative risk benefit (4.1 / 0.7 = 5.9)ADR / Relative risk benefit (4.1 / 0.7 = 5.9)

Risk must > 5.9 for a favourable risk profileRisk must > 5.9 for a favourable risk profile

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Evidence based medicineEvidence based medicineHigh risk and warfarin?High risk and warfarin?

CHAD2 SCORE > 3 - a stroke risk of 9 %CHAD2 SCORE > 3 - a stroke risk of 9 %

Stroke risk – on Warfarin (9 – (0.7 * 9)) = 2.7Stroke risk – on Warfarin (9 – (0.7 * 9)) = 2.7


The major bleed risk is 4.9% pa (NNH 20.4)The major bleed risk is 4.9% pa (NNH 20.4)

Risk equivalence (4.1 / 0.7) – stroke rate of 5.9%Risk equivalence (4.1 / 0.7) – stroke rate of 5.9%

Warfarin no difference 68.5% - ((100 – 45) + 13.5))Warfarin no difference 68.5% - ((100 – 45) + 13.5))

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Evidence based medicineEvidence based medicineIs aspirin a rational choice ?Is aspirin a rational choice ?

Aged 80 yr (atrial fib) has a 5 yr stroke risk of 15%Aged 80 yr (atrial fib) has a 5 yr stroke risk of 15%

Aspirin will reduce that risk by 20%Aspirin will reduce that risk by 20%

No event in 85% + 12 events not preventedNo event in 85% + 12 events not prevented

Aspirin will make no difference 97% of the timeAspirin will make no difference 97% of the time

Absolute risk reduction (ARR) – 0.6 (NNT 166.6)Absolute risk reduction (ARR) – 0.6 (NNT 166.6)

The average bleed risk is 0.2% x 5 = 1%The average bleed risk is 0.2% x 5 = 1%

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Evidence based medicineEvidence based medicinePatient preferences ?Patient preferences ?

Malcolm Man-Son-Hing, Malcolm Man-Son-Hing, et alet al, , Medical Decision Medical Decision

MakingMaking 2005: 2005: 2525;; 548-559 548-559 (Systemic review n = 8) (Systemic review n = 8)

FFewer patients ewer patients opt for opt for warfarin compared with warfarin compared with

guidelines ( 5 / 8 studies)guidelines ( 5 / 8 studies)

AspirinAspirin stroke rate of 1 stroke rate of 1 %% , opt for , opt for warfarinwarfarin 50% 50%

Aspirin stroke rateAspirin stroke rate 2 2% ,opt for % ,opt for warfarinwarfarin 66% 66%

Aspirin stroke rate 2 – 6% in 3 to choose warfarinAspirin stroke rate 2 – 6% in 3 to choose warfarin

PPhysicians balance patient preferences with hysicians balance patient preferences with Rx Rx

recommendations recommendations ofof clinical practice guidelines clinical practice guidelines

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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

bs evidence based medicine and atrial fibrillation

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