Geriatric Grand Rounds

TIA; underrecognized, undertreated

Tuesday, March 25, 2008 12:00 noon

Ashfaq Shuaib MD FRCPC FAHA Dr. Bill Black Auditorium Glenrose Rehabilitation Hospital Visit the following web sites:

Professor of Neurology and Director of the Stroke Program University of Alberta, Edmonton, Canada

For handouts, poster, schedule, subscription: http://www.ualberta.ca/~geriatri/ggr/. For onon-demand archive of previous presentations: http://www.beamtelehealth.ca

Competing Interests Declaration • Competing interests – I co-chair the steering committee of the SENTIS trial and am an advisor to CoAxia

• In the past 5 years, I have received speaker fees from: • Sanofi-Aventis/BMS, BI, Pfizer, Merck, Roche, Servier, AstraZeneca

• In the past 5 years, I have served on advisory boards for: • AstraZeneca, BI, Sanofi-Aventis/BMS, Roche, Pfizer

Learning Objectives 1. To demonstrate that the risk of stoke is “front-loaded” in patients with TIAs and minor strokes 2. To offer an investigation protocol whereby high risk patients can be identified 3. To present very recent evidence showing that early and aggressive treatment of TIAs can lead to a significant reduction in stroke & CVD

1

Stroke in Canada

Prevalence of stroke

• Prevalence ~ 5% of population over 65 Percent of Population

•

3rd

14

leading cause of death

• 70% of survivors need help with ADL’s • Gender disparity – 8.6% of deaths in women

12.0

12

11.5

10 8

6.6 6.3

6 4 2

0.4

0.3

1.1 0.8

1.2

3.1 3.0

2.1

0 20-34

35-44

– 5.6 % in men

45-54

55-64

65-74

75+

Ages

– Women have longer length of stay and more likely to be discharged to institutional care

Men

Women

Figure 1. Hospital Incidence Rate of Stroke by type and age, men

Case presentation

180 160 140 120 100 80 60 40 20 0

• 72 year old male with mild untreated hypertension and high cholesterol (lipitor 10 mg)

per 10,000

Rate

and women combined, per 10,000, Canada, 1999/00.

• Presents with speech difficulty and right sided weakness …fluctuating 90+

85

80

75

70

65

60

55

50

45

40

35

30

25

20

Five year age group

• CT and Doppler • Course in ER

Subarrachnoid hemorrhage (ICD-9= 430) Intracerebral hemorrhage (ICD-9= 431) Cerebral infarction (ICD-9= 434, 436) Acute stroke (ICD-9= 430, 431, 434, 436)

2

CT

What to do next with the patient? • Discharge him and have him come to the SPC ?? • Further investigations ?? • Any additional treatment options ??

Learning Objectives 1. To demonstrate that the risk of stoke is “front-loaded” in patients with TIAs and minor strokes 2. To offer an investigation protocol whereby high risk patients can be identified 3. To present very recent evidence showing that early and aggressive treatment of TIAs can lead to a significant reduction in stroke & CVD

Clinical significance of TIAs • 30-40% of strokes are preceded by a TIA or a minor stroke ( Lancet Neurology 2006;5:323-31) • After a TIA the 90 day risk of stroke is as high as 10.5% and half could occur in the first 2 days. (JAMA 2000; 284:2901-06)

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Stroke Free Interval After First Stroke Rochester, Mn 95%

100

90%

“Relaxed…”

Expected

80 60.7% 70.8%

60 40

Observed

Risk: 55-15%/year

20

mean age 74.5 yrs

1

2

3

4

5

6

7

8

9

10 yrs Neurology 1998

90 Day Prognosis after ED Dx of TIA

Can this be supported by additional evidence ? Can we stratify patients into high and low risk groups ?

Johnston SC, JAMA 2000;284:2901-2906

4

Age Sym duration Type of symptoms Risk factors

Johnson et al JAMA 2000

Impending Doom…

Is there a simple way to identify patients at high risk?

5

The ABCD score to stratify risk • Validity of ABCD system in other population groups (Stroke 2006;37:1710-1714)

ABCD 2 Score • Age ≥ 60 years = 1 point • BP ≥ 140/90 = 1 point • Unilateral weakness = 2 points

• ABCD 2 scoring system ( Lancet 2007;369:28392)

• California + ABCD system validated in 4 population groups in US and UK

• Speech impairment without weakness = 1 point • Duration ≥ 60 minutes = 2 points • Duration 10-59 minutes = 1 point • Diabetes = 1 point

ABCD 2 score Score

2-day risk

• High risk

6-7

8.1%

• Moderate risk

4-5

4.1%

• Low risk

0-3

1.0% Rothwell Lancet 2006 Rothwell et all Lancet 2006

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Conclusions Obj. 1 • Patients with TIAs are at a very high risk of EARLY completed ischemic stroke • Current knowledge can identify patients at the highest risk ( stroke in the initial 48 hours) … patients who may likely require admission to hospital

Learning Objectives 1. To demonstrate that the risk of stoke is “front-loaded” in patients with TIAs and minor strokes 2. To offer an investigation protocol whereby high risk patients can be identified 3. To present very recent evidence showing that early and aggressive treatment of TIAs can lead to a significant reduction in stroke & CVD

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Which Tests Should We Perform Speech, motor, >10 min, age >60, diabetes

Very early imaging the neck vessels is essential in all patients Your choice of Doppler, CTA or MRA

Gladstone D et al. CMAJ. 2004 Mar 30;170(7):1099-104.

TIA and CT TIA population 67% CT performed 4% : 13/322 had evidence of infarct on CT.

What about CT scan?

Odds Ratio 4.06 (1.16-14.14) for risk of stroke if infarct evident on CT. Important to rule out other disease

Stroke. 2003 Dec;34(12):2894-8.

8

Kaplan-Meier life-table analysis of survival free from stroke for patients with (dotted line) and without (solid line) new infarct on head CT 10%

And if you want to get fancy with investigations

38%

MRI and TCD for emboli monitoring

Ischemic injury and brain at risk common in TIA

Event Free Survival Curve for New Stroke Couttts SB et al. Annals of Neurology 2005;57:848-854

Kidwell C et al. Stroke 1999; 6:1174-1180. Couttts SB et al. Annals of Neurology 2005;57:848-854 Krol A et al. Stroke 2005

~50% of all TIA’s are associated with DWI abnormality. Especially if symptoms last > 1 hour or those with motor or speech deficits.

1.0

No DWI Lesion & No Occlusion

4

0.9

Yes DWI Lesion & No Occlusion

10

Yes DWI Lesion & Yes Occlusion

32

0.8 0.7

Likelihood ratio test p-value = 0.02

0.6 0.0

Even brief symptoms cause areas of permanent injury

0

30

60

90

Days after Presenting Acute TIA or Minor Stroke

9

FLAIR

ADC

DIFFUSION

MRA

10

Clinical Classification • Crescendo TIAs • TIAs with imaging showing evidence of CI • High risk TIAs • Low risk TIAs • Asymptomatic carotid disease

Conclusions Obj 2 • Immediate investigations are essential in patients with recent TIAs • Investigations help identify patients at the highest risk of early stroke • It is important to rule out (or in) significant symptomatic carotid stenosis or atrial fibrillation

Treatment of TIAs Learning Objectives 1. To demonstrate that the risk of stoke is “front-loaded” in patients with TIAs and minor strokes 2. To offer an investigation protocol whereby high risk patients can be identified

How to reduce the risk of early stroke in high risk patients?

3. To present very recent evidence showing that early and aggressive treatment of TIAs can lead to a significant reduction in stroke & CVD

Is there evidence that such strategies work?

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TIAs and Therapy What is new in treatment of TIAs

•

Rapid evaluation and observation of high risk TIA patients

•

Antiplatelet agents

•

BP control

• SOS-TIA

•

Statins

• FASTER

•

Anticoagulants (cardioembolic TIAs)

•

Early revascularization in presence of significant ICA disease

• EXPRESS

12

statin

clopidogrel

1st BP drug

2 BP drugs

13

SOS-TIA trial • Paris area study (Jan 2003 - Dec 2005) • 1085 suspected TIA, majority seen within 20 hours from onset • Outcome: 90 day stroke, MI and vascular death

14

Treatment of our patient

Clinical Classification

• Initial treatment: ASA 81 mg per day

• Crescendo TIAs

• Increased Atorvastatin to 40 mg per day

• TIAs with imaging showing evidence of CI

• Add Clopidogrel 75 mg per day

• High risk TIAs • Low risk TIAs • Asymptomatic carotid disease

TIA Prognosis: Benign

Malignant

Timing

days to wks

10 minutes

Frequency Sensory

multiple

one to few

Summary Obj 3

yes with positive sx

no

Motor

no

yes

Speech

no

aphasia?

Risk factors

no

Htn, DM, bruit?

Sympt ICA stenosis

no

yes

• Early treatment with appropriate antithrombotic agents (including combination therapy in some high risk patients)

yes

• Effective early management of risk factors

Intracranial disease

no

CT

no infarct

infarct

MRI

no DWI no occlusion

DWI + multiple DWI

• Diagnosis of conditions that may require alternate therapy (AF and carotid stenosis)

PWI abnormality carotid stenosis Discharge to clinic

Admit/intervene

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What are our plans in Edmonton • Move high risk TIAs to “critical care line” • Work with Diagnostic Radiology for access to immediate investigations of the high risk patient • Offer effective treatment, including risk factor management by the stroke team • Monitor our patients for outcomes

Overall summary Slide • Recognize, investigate and treat TIAs early and urgently • Risk factor management critical in primary and secondary prevention • Best results if management initiated in the first visit (preferably within initial 24 hours)

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