1

Determining the Risk of Stroke in AF

Lalit Kalra

Professor of Stroke Medicine

Dept of Basic and Clinical Neurosciences

King’s College London

PAF, diagnosed opportunistically 2 yrs ago

Type 2 Diabetes, Hyperlipidemia, NSTEMI 5 years agoNon-smoker, Drinks half a bottle of wine a day

DH: Metformin, Ramipril, Simvastatin, Aspirin

Pulse 78 reg, BP= 150/84, no signs of CCF or heart murmurs

Bloods: Normal FBC, LFTs, Glu, electrolytes, Cr (eGFR 52ml/min)

Normal TFT

ECG + 24 h ECG: NSR7 day event recorder ECG: X3 paroxysmal AF > 30sec, asymptomatic

Echo: Preserved LV systolic function – EF 60%, Moderate LA enlargement 4.2cm, no valve abnormalities

Mrs W-T 69 yrs F

2

Questions:

What are the risks of this patient suffering an ischaemic stroke?

How will you assess the risk?

Is there a difference in risk of an ischaemic stroke between persistent and paroxysmal AF?

Dec 2011

Atrial FibrillationStratification of stroke risk: CHADS2 score

Gage BF et al. JAMA 2001;285:2864–2870

Score

CHF or LV dysfunction 1

Hypertension 1

Age >75 years 1

Diabetes 1

Stroke/TIA 2

CHADS2 score

Adjusted Stroke Rate

(per 100 pt years)

0

4

8

12

16

20

0 1 2 3 4 5 6

3

Stroke risk assessment with CHA2DS2-VASc

CHA2DS2-VASc criteria Score

Congestive heart failure/left ventricular dysfunction

1

Hypertension 1

Age ≥75 yrs 2

Diabetes mellitus 1

Stroke/transient ischaemic attack/TE

2

Vascular disease(prior myocardial infarction, peripheral artery disease or aortic plaque)

1

Age 65–74 yrs 1

Sex category (i.e. female gender)

1

CHA2DS2-VASc total score

Rate of stroke/other TE (%/year)*

0 0.0

1 1.3

2 2.2

3 3.2

4 4.0

5 6.7

6 9.8

7 9.6

8 6.7

9 15.2

* Theoretical rates without therapy: assuming that warfarin provides a 64% relative reduction in TE risk (2.7% ARR), based on Hart et al.

Stroke risk persists even in asymptomatic/paroxysmal AF

The risk of stroke with asymptomatic or paroxysmal AF is comparable to that with permanent AF

Annual risk

of

stro

ke (

%)

Observed rate of ischaemic stroke

Stroke risk category

Low Moderate High0

2

4

6

8

10

12

14 Intermittent AF

Sustained AF

4

Antithrombotic strategy: what are the options?

1. Continue aspirin

2. Stop aspirin and commence oral anticoagulation

3. Others

Limited efficacy of Aspirin in reducing the risk of stroke in patients with AF

Random effects model; Error bars = 95% CI; *P>0.2 for homogeneity; †Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic); QOD = every other day

RRR (%)†

100 –10050 0 –50

AFASAK

SPAF

EAFT

ESPS II

Aspirin better Placebo better

LASAF125 mg/d

125 mg QOD

UK-TIA300 mg/d

1200 mg/d

JAST

All trialsRRR = 19%*

(95% CI: –1 to 35%)

8

5

Low dose aspirin in low risk patients

Kaplan-Meier survival curves for primary end points (a) and for primary plus secondary end points (b).

Aspirin associated with an increased risk of major bleeding (7 patients; 1.6%) compared with the control group (2 patients; 0.4%;p= 0.101).

Primary:cardiovascular death, stroke or TIA

Secondary:non-cv death, ICH, major bleeding, and peripheral embolisation.

Warfarin reduces the risk of stroke in NVAF

Random effects model; Error bars = 95% CI; *P>0.2 for homogeneity; †Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic)

Warfarin better Placebo better

RRR (%)†100 –10050 0 –50

AFASAK

SPAF

BAATAF

CAFA

SPINAF

EAFT

All trialsRRR 64%*

(95% CI: 49−74%)

6

Warfarin v Aspirin for stroke prevention in NVAF

Random effects model; error bars = 95% CI; *P>0.2 for homogeneity; †Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic)

RRR (%)*

100 –10050 0 –50

AFASAK I

AFASAK II

EAFT

PATAF

Warfarin better Aspirin better

Chinese ATAFS

SPAF IIAge ≤75 yrsAge >75 yrs

All trialsRRR 38%

(95% CI: 18–52%)

OAC v ASPIRIN in patient >75 yrs

973 patients aged 75 years with AF

Warfarin (INR 2–3) or aspirin (75 mg/day)

Follow-up for 2·7 years

Primary endpoint: fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism

7

Dec 2011

HAS-BLED risk criteria Points awarded

Hypertension 1

Abnormal renal and liver function (1 point each) 1 or 2

Stroke 1

Bleeding 1

Labile INRs 1

Elderly (e.g. age >65 years) 1

Drugs or alcohol (1 point each) 1 or 2

Maximum 9 points

INR = international normalised ratio

Assessment of bleeding risk

Dec 2011

ESC Guidelines for AC in AF

Aspirin plus clopidrogel or, less effectively, aspi rin only, should be considered in patients who refuse any OAC or cannot tolerate anticoagulants for reasons unrelated to bleeding

8

Offered Warfarin, risks and benefits explained

Declined:

• “told” risk not high with PAF

• unwilling to have regular blood tests

• anxious regarding risk of bleeding

• Concern about lifestyle changes

“Best” treatment option for Mrs W-T

Presented to ED 4/12 later with acute onset of:

• Left face, arm and leg weakness

• Dysarthria

• L visual and sensory inattention

NIHSS = 9, BP=160/90, BM=5.2 mmols

What happened next to Mrs W-T

9

Management

IV rtPA treatment successful

Patient returned to normal at 24hrs

10

Antithrombotic strategy: what would you do next?

1. Offer oral anticoagulation

2. Offer NOAC

3. Other

What should we do next for Mrs J-T?

69 yr female with PAF

T2DM (metformin)

Half a bottle of wine/day

Recent stroke on Aspirin

The story continues

Presents to ED 2/12 later

– Not feeling well

– Headache and malaise

– Difficulty in walking, no falls

– Dysarthric and confused

Bilateral weakness, sensation difficult to assess

Upgoing plantars

ITTR < 60%, INR > 5 x2 since discharge

INR 4.4

69 yr female with PAF

T2DM (metformin)

Half a bottle of wine/day

Recent stroke on Aspirin

Now warfarinised

11

Dec 2011

Warfarin utilisation in practice

0 500 1000 1500 2000

Survival to stroke (days)

0.6

0.7

0.8

0.9

1.0

Cu

mu

lati

ve

su

rviv

al

71–100%

Warfarin group

61–70%

51–60%

41–50%

31–40%

<30%

Non warfarin

There are no guidelines for the management of symptomatic chronic SDH

– surgical evacuation if clot thickness ≥10 mm

– Conservative management for 30 to 45 days, may produce complete recovery alone

Managed conservatively, improved

12

Dec 2011

Stroke risk assessment with CHA2DS2-VASc

CHA2DS2-VASc criteria Score

Congestive heart failure/left ventricular dysfunction

1

Hypertension 1

Age ≥75 yrs 2

Diabetes mellitus 1

Stroke/transient ischaemic attack/TE

2

Vascular disease(prior myocardial infarction, peripheral artery disease or aortic plaque)

1

Age 65–74 yrs 1

Sex category (i.e. female gender)

1

CHA2DS2-VASc total score

Rate of stroke/other TE (%/year)*

0 0.0

1 1.3

2 2.2

3 3.2

4 4.0

5 6.7

6 9.8

7 9.6

8 6.7

9 15.2

* Theoretical rates without therapy: assuming that warfarin provides a 64% relative reduction in TE risk (2.7% ARR), based on Hart et al.

HAS-BLED risk criteria Points awarded

Hypertension 1

Abnormal renal and liver function (1 point each) 1 or 2

Stroke 1

Bleeding 1

Labile INRs 1

Elderly (e.g. age >65 years) 1

Drugs or alcohol (1 point each) 1 or 2

Maximum 9 points

INR = international normalised ratio

Assessment of bleeding risk

13

Dec 2011

What would you do for secondary prevention?

Switch back to aspirin

Start aspirin and clopidrogel

Continue anticoagulation

Other

Dec 2011

ACTIVE: Dual antiplatelet therapy is superior to Aspirin alone but inferior to Warfarin

ACTIVE Investigators. N Engl J Med 2009;360:2066–78

Aspirin aloneAspirin (75–100 mg/d)

Dual antiplatelet therapyClopidogrel (75 mg/d) + Aspirin (75–100 mg/d)

HR 0.72(95% CI: 0.62–0.83)

P<0.0001

Stroke

Cum

ula

tive

inci

dence

Years

0.15

00.00

1 2 4

0.10

0.05

3

26

Oral anticoagulationVKA (target INR = 2.0–3.0)

RR 1.72(95% CI: 1.24−2.37)

P=0.001

14

Balancing risk using the CHADS2-VASc and HAS-BLED scores

Anticoagulation for AF in perspective

28

Meta-analysis of ischaemic stroke or systemic embolism

Favourswarfarin

Favoursother treatment

Warfarin vs.:

Placebo

Low-dose warfarin

Aspirin

Aspirin + clopidogrel

0.0Hazard ratio

2.00.5 1.0 1.5

Dabigatran (H), Apixaban

Dabigatran (L) Rivaroxaban

15

ICH: Novel agents v warfarin

Dec 2011

Left atrial ablation (LAAB)

Restoration of NSR

Reduction in stroke risk

Reduced need for anti-arrhythmic drugs

No/reduced need for lifelong anticoagulation

Restoration of mechanical function

Reversal of inflammation and EF (AF begets AF)

Reversal of hypercoagulation disorder

16

Dec 2011

LAAB as treatment for abolishing AF

Freedom for AF: 85% PAF, 72% persistent AF

Number of procedures:

– 1 procedure 46%

– 2 procedures 36%

– 3 procedure 13%

– 4 or more procedures 5%

75% of PAF and 60% of Persistent AF off anti-arrhythmics

OAC may not be required if sustained NSR (low CHADS risk)

Key messages

NVAF incl PAF is associated with high risk of stroke

All patients with AF need risk stratification for AC

Risk stratification needs to be individualised to patients

– Stroke and bleeding risk (CHADS-VASC and HASBLED)

– Lifestyles and concordance with treatment

Lower threshold for OAC, those with ≥1 stroke risk factors are eligible (ESC guidelines)

Suboptimal assessment or prevention INCREASES the risk of stroke or bleeding