Secondary Stroke Prevention - Sunnybrook Hospital · R.H.Swartz, University of Toronto. • To review basic epidemiology of stroke and rationale for stroke prevention efforts •

R.H.Swartz, University of Toronto.

Secondary Stroke Prevention

Acute stroke conference,

Sunnybrook EstatesJanuary 20, 2011

Rick Swartz HBSc, MD, PhD, FRCPC

Assistant Professor, Department of Medicine,

Divisions of Neurology and Obstetrical Medicine,

Director, University of Toronto Stroke Program

Sunnybrook Health Sciences Centre, University of Toronto

[email protected]

Disclosures

Salary support:

• Heart and Stroke Foundation Centre for Stroke Recovery

• CIHR/CSN “Focus on Stroke”

Advisory Boards:

None.

Speaker’s Honararia:

GTA stroke conference, Ontario Stroke Day.

Bristol-Myers Squibb Canada

Trials:

None.

No stock in pharmaceutical companies



• To review basic epidemiology of stroke and

rationale for stroke prevention efforts

• To review secondary prevention strategies and

outline an approach to the art & science of

secondary prevention

Objectives

Stroke is a “brain attack”

R.H.Swartz, University of Toronto

• sudden loss of specific brain functions from

damage to one part of the brain secondary to:

• an interruption of that region’s blood supply

(ischemic ~ 85%)

OR

• bleeding into that area of brain

(hemorrhagic ~15%)


http://www.strokecenter.org/

Basic epidemiology of stroke


• 1 stroke every 10 minutes in Canada

• #1 leading cause of adult disability in Canada

• 2nd leading cause of death worldwide

• Overall, ~20% fatal; 60-75% some disability

• ~50,000 Canadians annually have strokes

resulting in death or serious disability.

http://www.canadianstrokenetwork.ca/

World Stroke Day Proclamation, Stroke 2008;39

http://www.canadianstrokenetwork.ca/

Outcome of Stroke

Adapted from Stegmayr B, et al. Stroke 1997;28:1367-1374

About 50% are either dead or disabled

Prognosis of hemorrhage is worse

Adapted from Hacke 1998, Asplund, 1997

Stroke outcome in round numbers

• For every 10 stroke patients…

• 2 will die

• 2 will recover

• 6 will be left with disability

ICES data, 2001

Dr. David Gladstone, 2004

Basic epidemiology of stroke


• ~300,000 Canadian survivors live at risk for:• another stroke (20% in 2 years)

• post-stroke dementia & post-stroke depression.

• < 50% survivors return to work… lost income.

• 50% caregivers develop emotional illness

within 1 year (care for the caregivers).

• Estimated direct and indirect costs of stroke are

~$4 BILLION annually in Canada.http://www.canadianstrokenetwork.ca/

So…


• Strokes are common (and “silent” strokes = 3x symptomatic!)

• Strokes kill and disable people.

• Fortunately, some of this burden is also

preventable

• Stroke is common, serious and treatable…

we can make a difference

A brief interlude for motivation…


• We will “cure” more people by aggressively

managing risk factors than we will EVER cure

with tPA.

http://www.strokebestpractices.ca/

Primary Prevention of Stroke


• Primary prevention means treating us…

modifying risk factors before symptoms or

illnesses occur (individuals & populations)

• We treat far more people for primary prevention,

and the event you’re trying to prevent is rarer.

• Thus, treatments have to be VERY safe and

effective in populations.

Primary Prevention of Stroke (& heart disease)


• Blood pressure lowering

• Atrial fibrillation (CHADS2)

• Smoking cessation

• Diabetes treatment

• Cholesterol treatment

• Weight loss / abdominal obesity / exercise

• Low-risk drinking guidelines

http://www.preventstroke.ca Stroke. 2006;37:577-617

Secondary Stroke Prevention


• Treatment of those with prior stroke or TIA,

regardless of etiology

1) Why treat?

2) When to treat?

3) Who to treat?

4) What to treat?

• In people with TIAs discharged from ER:

• 12% are readmitted to hospital within 30 days

• 9 – 12% recurrent stroke or death within 30 days!• 9% for TIA with speech deficit

• 12% for TIA with motor deficit

• Also need to treat FAST…

Secondary Prevention 1) Why treat?

Gladstone et al. CMAJ 2004 R.H.Swartz, University of Toronto

Stroke After TIA Canadian Data (slide courtesy Dr. F. Silver)

9.5 % 14.5 %

21.8 %

Secondary Prevention 2) when?

When treat? Early Risk of Stroke After TIAGladstone et al. CMAJ 2004

Half of the strokes occurred in the first 2 days(slide courtesy Dr. D. Gladstone)

http://www.cmaj.ca/content/vol170/issue7/images/large/22ff2.jpeg

pooled analysis from population and RCT’s (OXVASC, OCSP, UK-TIA and ECST).

Rothwell & Warlow, Neurology, 2005;64:817-20.

23% of patients with ischemic stroke have had a TIA

before their stroke

• 17% occur the day of the stroke,

• 9% the previous day,

• 43% had a TIA during the 7 days prior to the

stroke.

2) When to treat?


• Phase 1 vs. 2

• 90-day stroke risk

from 10% to 2%

• Medications started

right away

• Carotid

endarterectomy

expedited

EXPRESS StudyRothwell et al. Lancet 2007

2) When to treat?


FASTER Kennedy et al. Lancet Neurology 2007

• Fast Assessment of Stroke and TIA to prevent Early

Recurrence

• ASA +/- clopidogrel +/- simvastatin in 24 hours

• Stroke risk: 10.8% vs. 7.1% in favour of

ASA/clopidogrel combination (n.s.)

2) When to treat? Urgent assessments

prevent stroke

SOS-TIA Lavallee et al. Lancet Neurol 2007

• 24 hours TIA unit had lower event rates than

expected from ABCD2 score (1.24% vs. 5.96%)

Age 1 point if >60 years

Blood pressure 1 point if sBP >140 or dBP >90

Clinical features 2 points for unilateral weakness; 1 point

speech deficit without weakness

Duration 2 points if >60 min; 1 point if >10-59 min

Diabetes 1 point

• 2-day stroke risk: 1% (0-3 points), 4% (4-5 points), 8% (6-7 points)

• 90-day stroke risk up to 25%

Secondary Prevention 3)Who to treat? Risk Stratification with ABCD2 vs. Motor or speech TIA’s

Johnston, Rothwell, et al. Lancet 2007; 369:283-92

• It isn’t always as simple as the “ABC’s”

• For example:

• 61 y.o. woman with mild HTN and diet controlled

DM, who had >2 hours of dizziness

• 58 y.o. man without diabetes or hypertension but had

a 15 minute episode of right face, arm and leg

weakness, with speaking gibberish and not

understanding speech.

Who to treat? The problem with ABCD’s

Gladstone et al. CMAJ 2004 R.H.Swartz, University of Toronto

3) Who to treat? Defining high risk.

Coutts et al., Int J. Stroke 2008; AnnNeurol 2005

ABCD2 + MRI (DWI / intracranial vessel occlusions)


The future of TIA Triaging?

1.

2.

3.

1) Look at the intracranial vessels: atherosclerosis,

moya-moya, inflammatory diseases

2) Look at the neck: Carotid stenosis, dissections…

3) Look at the heart: Atrial fibrillation (+/- valve etc.)

4) Look at the blood: Platelet, APLA etc.

5) Look at the patient: risk factor modification

(hypertension, high cholesterol, diabetes, smoking,

drinking, diet/exercise, social situation)

Secondary Prevention 4) What to treat?


3-Month Stroke Risk

According to Etiological SubtypeLovett et al. Neurology 2004: meta-analysis, n=1709

3

9

12

19

0

5

10

15

20

TOAST Classification

Per

cen

tage

small

vesselunknown cardiac large

vessel

(slide courtesy Dr. D. Gladstone)

What to treat: A) Symptomatic Carotid Stenosis

• Severe stenosis (70-99%)

surgery highly beneficial (NNT=3*)

• Moderate stenosis (50-69%)

surgery beneficial (NNT=7*)

• Mild stenosis (<50%) – No surgery


Timing of Carotid SurgeryRothwell et al. Lancet 2004

NNT to prevent one stroke

at 5 years:

NNT = 5 if surgery within 2

weeks

NNT = 125 if surgery

delayed >3 months!


Management of “Surgical” Carotid Disease

• 2008 Canadian Best Practice Recommendations

• TIA or non-disabling stroke and ipsilateral 70%–99% ICA

stenosis should be offered carotid endarterectomy within 2

weeks unless contraindicated

• Appropriate antiplatelet therapy depends on timing:

• Surgery in ≤ 24 hours: consider ASA

• Surgery in 1-2 weeks: consider combination ASA +

clopidogrel

• Ensure optimal management of vascular risk factors

* CMAJ 2008;179(12 Suppl):S1-S25.

What to treat? B) Atrial Fibrillation


• Atrial fibrillation (CHADS2):

Atrial fibrillation increases stroke risk 3-5x

Higher risks: CHF, HTN, Age, DM, prior stroke/tia (2)

CHADS Score Risk Stroke Rate / yr Recommendation

0 low <2 % ASA 75-325mg/d

1 low-mod <2 % warfarin INR 2-3 OR ASA

2 mod 4 % warfarin INR 2-3

3 high 5.9 % warfarin INR 2-3

4 v. high 8 – 18 % warfarin INR 2-3

Gage et al, JAMA 2001;285(22):2864-2870

Stroke Prevention


10

20

30

50–59 60–69 70–79 80–89

AF prevalence

Strokes attributable to AF

Age (years)

Pre

vale

nce (

%)

Wolf, Stroke 1991;22:983-8

Strokes Attributable to Atrial Fibrillation

(slide courtesy Dr. F. Silver)

Warfarin: RRR in Stroke

Hart RG Ann Intern Med 131:492-501, 1999

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

SPINAF

CAFA

BAATAF

SPAF I

AFASK

All Patie

nts

Gladstone et al, Stroke 2009

• Blood pressure: Common. >2/3 of adults >65

• The most important modifiable risk factor (2-5 x)• Ischemic, bleeding, “silent strokes”

• Contributes to:• Large-vessel atherosclerotic disease

• Small-vessel (lacunar) disease

• LV dysfunction and Afib

• Untreated HTN increases stroke risk 3-4 times. Treatment can

reduce stroke risk and fatalities ~40%.

• Most patients require 2 or more agents

• CHEP guidelines <140/90 (or if diabetes <130/80)

4) What to treat? C) Vascular risks


http://www.preventstroke.ca http://www.americanheart.org/presenter.jhtml?identifier=4704Stroke. 2006;37:577-617

• Diabetes: ~2x increased risk of stroke. Highly

correlated w/ HTN, high cholesterol, weight and

sedentary lifestyles. Target HbA1c <0.07. Treatment

reduces microvascular complications > macrovascular.

• Cholesterol: 2x increased risk of stroke. Risk for

CAD (which independently also increases stroke risk).

SPARCL (NNT = 50)


R.H.Swartz, University of Torontohttp://www.preventstroke.ca

http://www.americanheart.org/presenter.jhtml?identifier=4704

Stroke. 2006;37:577-617


• Smoking:

• 2 – 6 x risk (2x with second hand smoke only);

normalizes >5 yrs, independent of age

• one-time advice from physician results in 2% of

smokers quitting for >1 yr

• Weight loss, exercise, abdominal obesity: 2-6x

increased stroke risk with obesity. Treatments: low-

calorie, low-fat, low-sodium diet, 20-30 minutes of

moderate exercise most days

http://www.preventstroke.ca



• Anti-platelets (Aspirin (ASA), Clopidogrel (Plavix),

ASA/ER-dipyridimol (Aggrenox)):

• Low-dose ASA 1o prevention in people at risk

• increases GI bleed & hemorrhagic stroke risk.

• 75–160 mg daily as effective as higher doses.


Stroke. 2006;37:577-617



• Deciding between anti-platelets?!

• CAPRIE (ASA vs. Plavix), CURE (Plavix/ASA vs

placebo/ASA post-ACS), ESPS2 and ESPRIT (ASA

plus ER dipyridamole vs. ASA)

• MATCH (Plavix vs. ASA/plavix): bleeding higher w/

combined ASA/Plavix (risk increases with long-term

use)

• PROFESS: no decisions between Plavix and Aggrenox


Stroke. 2006;37:577-617


Stroke Prevention


• Smoking cessation:

• 2 – 6 x increased risk (2x with second hand smoke);

normalizes 5 yrs after quitting, independent of age

• one-time advice from physician results in 2% of

smokers quitting for >1 yr

• Weight loss, exercise, abdominal obesity: 2-6x

increased stroke risk with obesity. Treatments: low-

calorie, low-fat, low-sodium diet, 20-30 minutes of

moderate exercise most days

http://www.preventstroke.ca

Stroke Prevention


• We will “cure” more people by aggressively

managing risk factors than we will EVER cure

with tPA.

1) Look at the intracranial vessels: atherosclerosis,

moya-moya, inflammatory diseases

2) Look at the neck: Carotid stenosis, dissections…

3) Look at the heart: Atrial fibrillation (+/- valve etc.)

4) Look at the blood: Platelet, APLA etc.

5) Look at the patient: risk factor modification

(hypertension, high cholesterol, diabetes, smoking,

drinking, diet/exercise, social situation)

Secondary Prevention: What to treat?


Summary: Stroke Prevention

• Strokes are common and serious

• We can identify high risk patients

• We have effective stroke prevention therapies

• But…current management is often suboptimal

• Primary prevention: do the things we should do anyway

• Secondary prevention:

• Look at the brain vessels, neck, heart, blood and patient

• Treat TIA’s early and aggressively

• Expedite surgery for symptomatic carotid artery disease

• Anticoagulate patients with atrial fibrillation

• Anti-platelets and other risk reduction for everyone else!

Documents

Secondary Stroke Prevention - Sunnybrook Hospital · R.H.Swartz, University of Toronto. • To review basic epidemiology of stroke and rationale for stroke prevention efforts •