Preventing Stroke in Preventing Stroke in Primary CarePrimary Care

Clinical recommendations Clinical recommendations from the Alberta Provincial from the Alberta Provincial

Stroke StrategyStroke Strategy

Learning ObjectivesLearning Objectives Upon completion of this program, Upon completion of this program,

participants will be able to:participants will be able to:

Discuss the incidence of stroke and the risk of Discuss the incidence of stroke and the risk of recurrent strokerecurrent stroke

Describe four components of secondary stroke Describe four components of secondary stroke preventionprevention

Identify high risk TIA/stroke patients along with Identify high risk TIA/stroke patients along with the appropriate care and investigationsthe appropriate care and investigations

Explain strategies to reduce the risk of recurrent Explain strategies to reduce the risk of recurrent strokestroke

Stroke: The Canadian Stroke: The Canadian PerspectivePerspective

50,000 new stroke patients/year in Canada50,000 new stroke patients/year in Canada††

1 stroke every 10 minutes1 stroke every 10 minutes 5000 new strokes / year in Alberta5000 new strokes / year in Alberta

200,000–300,000 stroke survivors in 200,000–300,000 stroke survivors in CanadaCanada††

35-40,000 stroke survivors in Alberta35-40,000 stroke survivors in Alberta

Cost to Alberta Health over $300 million / Cost to Alberta Health over $300 million / yearyear

Stroke: The Canadian Stroke: The Canadian PerspectivePerspective

4th leading cause of death in Canada4th leading cause of death in Canada

The leading cause of adult disabilityThe leading cause of adult disability

28% of stroke patients are under age 28% of stroke patients are under age 65*65*

Stroke SubtypesStroke Subtypes

Ischemic 80%Ischemic 80%Hemorrhagic Hemorrhagic

20%20%

Athero-thrombosis: a Athero-thrombosis: a progressive processprogressive process

NormalFatty

streakFibrousplaque

Athero-scleroticplaque

Plaquerupture/fissure &

thrombosis

Myocardial infarction

Ischaemicstroke

Critical leg ischaemia

Clinically silent Cardiovasculardeath

Increasing ageIncreasing age

AnginaTransient ischaemic attack

Claudication/PAD

Recurrence of Ischemic Recurrence of Ischemic StrokeStroke

From Petty GW et al. Stroke 2000;31:1062-68

†Not significant; all other categories statistically different across subtype of stroke.

Outcomes Atherosclerotic Cardioembolic Lacunar Unknown cause

Mortality at 30 d 8.1% 30.3% 1.4% 14.0%†

Mortality at 5 y 32.2% 80.4% 35.1% 48.6%

Recurrent stroke at 30 d

18.5% 5.3% 1.4% 3.3%

Recurrent stroke at 5 y

40.2% 31.7% 24.8% 33.2%†

Good function at 1 y

53.4% 26.7% 81.9% 50.3%

Outcomes for Patients With a First Ischemic Stroke (by subtype)

Second StrokesSecond Strokes

Stroke or TIA survivors have an increased Stroke or TIA survivors have an increased risk of a subsequent strokerisk of a subsequent stroke

Recurrent strokes are more likely than initial Recurrent strokes are more likely than initial strokes to result in disability and death strokes to result in disability and death

~ 20%-40% of strokes are preceded by a TIA ~ 20%-40% of strokes are preceded by a TIA or non disabling strokeor non disabling stroke

(Rothwell et al. Lancet Neurol 2006; 5: 323-331)(Rothwell et al. Lancet Neurol 2006; 5: 323-331)

Golden Opportunity for Stroke Prevention!Golden Opportunity for Stroke Prevention!

TIA Stroke RiskTIA Stroke RiskRisk of stroke following TIA is high:Risk of stroke following TIA is high:

10-20% within 90 days10-20% within 90 days 50% of these within the first 2 days (48 50% of these within the first 2 days (48

hours)hours)

Johnston et al. JAMA 2000; 284: 2901-06Johnston et al. JAMA 2000; 284: 2901-06

EARLY PREVENTION STRATEGIES EARLY PREVENTION STRATEGIES can make a difference!can make a difference!

ACT FAST!ACT FAST!

JAMA 2000;284:2901-2906

Kaplan-Meier Survival-Free from StrokePatients Presenting with TIA in Emergency Room (N=1707)

10.5%

High risk of stroke during 1st few days after TIA

ModifiableModifiable HypertensionHypertension DyslipidemiaDyslipidemia

DiabetesDiabetes Metabolic syndrome Metabolic syndrome

Atrial fibrillationAtrial fibrillation Cardiovascular DiseaseCardiovascular Disease TIA/prior strokeTIA/prior stroke Carotid stenosisCarotid stenosis

Cigarette smokingCigarette smoking Alcohol abuseAlcohol abuse ObesityObesity Physical inactivity Physical inactivity Obstructive sleep apneaObstructive sleep apnea

NonmodifiableNonmodifiable

AgeAge GenderGender Race/ethnicityRace/ethnicity HeredityHeredity

Goldstein L, et al. Circulation. 2001;103:163-182.Broderick J, et al. Stroke. 1998;29:415-421.Brown WV. Clin Cornerstone. 2004;6(suppl 3):S30-S34.

Risk Factors for StrokeRisk Factors for Stroke

Approach to Secondary Stroke Approach to Secondary Stroke PreventionPrevention

Components:Components:

Evaluate the EventEvaluate the Event

Implement InterventionsImplement Interventions

Initiate MedicationsInitiate Medications

Modify Stroke Risk Factor: Modify Stroke Risk Factor: Continuous MonitoringContinuous Monitoring

Evaluate the Evaluate the EventEvent

ABCDABCD22 Score ScoreRothwell et al. Lancet; 2007; 369: 283-292Rothwell et al. Lancet; 2007; 369: 283-292

Yes No

Age 60 yrs 1 0

Bp 140/90 1 0

Clinical Features Unilateral weakness 2 0

(with or without speech disturbance)

Speech deficit without weakness 1 0

Duration

> 10 min < 59 min 1 0

60 min 2 0

Diabetes 1 0

Score 4 = High Risk

Evaluate the Event: Evaluate the Event: TIA / Minor Stroke Risk AssessmentTIA / Minor Stroke Risk Assessment

TIA Stroke Risk AssessmentTIA Stroke Risk Assessment

High RiskHigh Risk

1. Symptom onset within the last 48 hours with any one of the 1. Symptom onset within the last 48 hours with any one of the following :following :

Motor deficit lasting more than 5 minutesMotor deficit lasting more than 5 minutes Speech deficit lasting more than 5 minutesSpeech deficit lasting more than 5 minutes ABCDABCD22 score ≥ 4 score ≥ 4

2. Atrial fibrillation with TIA2. Atrial fibrillation with TIA

Evaluate the Event: Evaluate the Event: TIA / Minor Stroke Risk AssessmentTIA / Minor Stroke Risk Assessment

TIA Stroke Risk AssessmentTIA Stroke Risk AssessmentMedium RiskMedium Risk

Symptom onset between 48 hours and 7 days with any one of the Symptom onset between 48 hours and 7 days with any one of the following :following :

Motor deficit lasting more than 5 minutesMotor deficit lasting more than 5 minutes Speech deficit lasting more than 5 minutesSpeech deficit lasting more than 5 minutes ABCDABCD22 score ≥ 4 score ≥ 4

Low RiskLow Risk1. Symptom onset > 7 days 1. Symptom onset > 7 days 2. Symptom onset ≤ 7 days without the presence of high risk 2. Symptom onset ≤ 7 days without the presence of high risk

symptoms symptoms Speech deficit, motor deficit, ABCDSpeech deficit, motor deficit, ABCD22 score ≥ 4, atrial fibrillation with TIA score ≥ 4, atrial fibrillation with TIA

** Isolated syncope or dizziness is rarely a TIA and may not ** Isolated syncope or dizziness is rarely a TIA and may not require Stroke Prevention Clinic Referral require Stroke Prevention Clinic Referral

Evaluate the Event: Evaluate the Event: InvestigationsInvestigations

Labs - Labs - CBC, lytes, Cr, gluc, PTT, INR, fasting CBC, lytes, Cr, gluc, PTT, INR, fasting lipidslipids

ECGECG ? Cardiac cause - afib? Cardiac cause - afib Holter monitorHolter monitor

CT or MRICT or MRI Rule out mimics, identify stroke typeRule out mimics, identify stroke type

Carotid Imaging (carotid dopplar, CTA Carotid Imaging (carotid dopplar, CTA or MRA)or MRA) Identify stenosisIdentify stenosis

EchocardiogramEchocardiogram If suspect cardiac causeIf suspect cardiac cause

IMPLEMENT IMPLEMENT

INTERVENTIONSINTERVENTIONSACT FAST WITH HIGH RISK ACT FAST WITH HIGH RISK

PATIENTS!PATIENTS!

SOS - TIA

EXPRESS study ( UK)EXPRESS study ( UK) PHASE 1 : daily appointment clinic , advice PHASE 1 : daily appointment clinic , advice

faxed to the FPfaxed to the FP PHASE 2 : Emergency clinic, TIA patients seen PHASE 2 : Emergency clinic, TIA patients seen

on the same day and treatment given in clinicon the same day and treatment given in clinic ASA in all cases, ASA + clopidogrel in high ASA in all cases, ASA + clopidogrel in high

risk patients, simvastatin 40mg, perindopril risk patients, simvastatin 40mg, perindopril 4mg and indapamide 1.25 mg4mg and indapamide 1.25 mg

Reduction in risk of early recurrent stroke by Reduction in risk of early recurrent stroke by over 80%over 80%

Rothwell et al. Lancet; 2007:370:1432-Rothwell et al. Lancet; 2007:370:1432-

14421442

Express Study

Implement Interventions: Implement Interventions: Carotid EndarterectomyCarotid Endarterectomy

If TIA due to ≥ 50% stenosis in If TIA due to ≥ 50% stenosis in extracranial carotid artery consider CEAextracranial carotid artery consider CEA

Greatest benefit if surgery within 2 weeksGreatest benefit if surgery within 2 weeks

Rothwell et al. Lancet; 2004; 363: Rothwell et al. Lancet; 2004; 363: 915-25915-25

Early Carotid Surgery Much Better >70% w/o near-Early Carotid Surgery Much Better >70% w/o near-occlusionocclusion

Rothwell PM et al. Stroke 2004;35:2855-2861.

NNT 3

To order pocket card: there is a link on APSS webpage underneath Professional Education Resources:http://www.strokestrategy.ab.ca/health-care-providers-ed.html:

Initiate Medications: Initiate Medications: Antithrombotic TherapyAntithrombotic Therapy

Aspirin (50-325 mg/day) is first line Aspirin (50-325 mg/day) is first line treatmenttreatment

If aspirin naïve- load with 160mg then If aspirin naïve- load with 160mg then 81 mg OD81 mg OD

OptionsOptions::

Aspirin/extended release dipyridamoleAspirin/extended release dipyridamole 25mg/200mg BID25mg/200mg BID

Clopidogrel Clopidogrel 75 mg OD, consider loading with 300 75 mg OD, consider loading with 300

mgmg

ESPS-2: The Second ESPS-2: The Second European European

Stroke Prevention StudyStroke Prevention Study Tested efficacy of ASA/ER DP for Tested efficacy of ASA/ER DP for

secondary stroke preventionsecondary stroke prevention Addressed clinical questionsAddressed clinical questions

Does ER DP prevent stroke? Does ER DP prevent stroke? Does low-dose ASA prevent stroke?Does low-dose ASA prevent stroke? Is ASA/ER DP superior to ASA alone? Is ASA/ER DP superior to ASA alone?

To ER DP alone?To ER DP alone? Is ASA/ER DP well tolerated?Is ASA/ER DP well tolerated?

Diener HC, et al. J Neurol Sci 1997;151:S1-S77Diener HC, et al. J Neurol Sci 1996;143:1-13

ESPS-2 Results:ESPS-2 Results:Stroke-Free SurvivalStroke-Free Survival

Kaplan-Meier stroke-free survival curves

ER DPASA/ER DPASAPlacebo

Pa

tient

s w

ithou

t str

oke

(%

)

Time (months)

80

85

90

95

100

6 12 18 24

Diener HC, et al. J Neurol Sci 1997;151:S1-S77Diener HC, et al. J Neurol Sci 1996;143:1-13

ESPS-2: ConclusionsESPS-2: Conclusions

Combined treatment with ER DP + Combined treatment with ER DP + ASA reduces the risk of stroke by ASA reduces the risk of stroke by 37% vs. placebo (p<0.001)37% vs. placebo (p<0.001)

Combined treatment with ER DP + Combined treatment with ER DP + ASA is significantly superior to ASA ASA is significantly superior to ASA alone (RRR 23.1%, p<0.006)alone (RRR 23.1%, p<0.006)

ER DP and ASA have an additive ER DP and ASA have an additive effect in secondary prevention of effect in secondary prevention of strokestroke

RRR: 6.4% (p=0.244)

ASA+Clopidogrel

Clopidogrel

IS, MI, VD, rehospitalisation for acute ischaemic event

Cum

ula

tive

eve

nt r

ate

0.00

0.04

0.08

0.12

0.16

0.20

Months of follow-up

0 3 6 9 12 15 18

MATCH: ASA+Clopidogrel showed a non significant trend for MATCH: ASA+Clopidogrel showed a non significant trend for the reductionthe reduction

in major vascular events in specific high risk cerebrovascular in major vascular events in specific high risk cerebrovascular patients*patients*

Primary Endpoint (ITT)

* All patients received clopidogrel

Initiate Medications: Initiate Medications: Antithrombotic TherapyAntithrombotic Therapy

If cardioembolic source: If cardioembolic source:

Long-term anticoagulation Long-term anticoagulation (Warfarin)(Warfarin)

Target INR 2.0 – 3.0Target INR 2.0 – 3.0

Atrial FibrillationAtrial Fibrillation

Persistent and PAF predictors of first Persistent and PAF predictors of first and recurrent strokesand recurrent strokes

Overall RR with coumadin is 68%Overall RR with coumadin is 68% Optimal INR 2-3Optimal INR 2-3 Estimated RR with ASA compared to Estimated RR with ASA compared to

placebo is 21%placebo is 21% About one-third with AF & IS will About one-third with AF & IS will

have another potential cause eg have another potential cause eg carotid stenosiscarotid stenosis

Stroke Prediction Model: CHADS Stroke Prediction Model: CHADS Scoring Tool Scoring Tool Risk Classification Scheme:Risk Classification Scheme:

Components of CHADS2Components of CHADS2

CHADS2 itemCHADS2 item PointsPointsCongestive heart failureCongestive heart failure 1 1Hypertension (systolic >160 mmHg) Hypertension (systolic >160 mmHg)

11Age greater than 75 yearsAge greater than 75 years 1 1DiabetesDiabetes 1 1Prior cerebral ischemiaPrior cerebral ischemia 2 2

Antithrombotic Therapy for Antithrombotic Therapy for Patients With Atrial Patients With Atrial

FibrillationFibrillationWeaker Risk FactorsWeaker Risk Factors Moderate-Risk Factors Moderate-Risk Factors High-Risk FactorsHigh-Risk Factors

Female genderFemale gender Age ≥ 75 yearsAge ≥ 75 years Previous stroke Previous stroke /TIA or /TIA or embolismembolism

Age 65 to 74 Age 65 to 74 HypertensionHypertension Mitral stenosisMitral stenosis

Coronary Artery DiseaseCoronary Artery Disease Heart FailureHeart Failure Prosthetic heart Prosthetic heart valvevalve

ThyrotoxicosisThyrotoxicosis LV ejection fraction ≤ 35% LV ejection fraction ≤ 35%

DiabetesDiabetes

ACC/AHA/ESC guide lines for management of AF; Circulation 2 Aug 06ACC/AHA/ESC guide lines for management of AF; Circulation 2 Aug 06

Antithrombotic Therapy for Antithrombotic Therapy for Patients With Atrial Patients With Atrial

FibrillationFibrillationRisk CategoryRisk Category Recommended TherapyRecommended Therapy

No risk factors ( ASR 1%)No risk factors ( ASR 1%) Aspirin, 81 Aspirin, 81 to 325 mg dailyto 325 mg daily

One moderate-risk factor (ASR 4%)One moderate-risk factor (ASR 4%) Aspirin, or Aspirin, or warfarin warfarin

Any high-risk factor or more than 1Any high-risk factor or more than 1 warfarin warfarin

moderate-risk factor (ASR 8-12%)moderate-risk factor (ASR 8-12%)

ACC/AHA/ESC guide lines for management of AF; ACC/AHA/ESC guide lines for management of AF; Circulation 2 Aug 06Circulation 2 Aug 06

Modifiable Stroke Risk Modifiable Stroke Risk Factors Factors

Medical conditionsMedical conditions HypertensionHypertension HypercholesterolemiaHypercholesterolemia ObesityObesity Diabetes mellitusDiabetes mellitus Insulin resistance?Insulin resistance? Cardiac diseasesCardiac diseases

Atrial fibrillationAtrial fibrillation Coronary artery Coronary artery

diseasedisease CHF CHF

BehavioursBehaviours Cigarette Cigarette

smoking smoking Heavy alcohol use Heavy alcohol use Physical inactivity Physical inactivity

1. Healthy diet; High in fresh fruits, vegetables and low fat dairy products, low in saturated fat and salt in accordance with the DASH diet

2. Regular physical activity: optimum 20-60 minutes of moderate cardiorespiratory activity 3-5/week or more

3. Reduction in alcohol consumption in those who drink excessively (<2 drinks/ day)

4. Weight loss (> 5 Kg) in those who are over weight (BMI>25)

5. Smoke free environment

Lifestyle RecommendationsLifestyle Recommendations

Lifestyle: Weight LossLifestyle: Weight Loss

Healthy BMI: Healthy BMI: 18.5-24.9 kg/m18.5-24.9 kg/m22

Waist circumference:Waist circumference: <102 cm for men, <88 cm for women<102 cm for men, <88 cm for women

? Insulin Resistance ? Insulin Resistance

(metabolic syndrome)(metabolic syndrome)

CAN ALL BARRIERS BE OVERCOME?CAN ALL BARRIERS BE OVERCOME?

Treating Hypertension to Treating Hypertension to Prevent StrokePrevent Stroke

HTN is the single most important HTN is the single most important modifiable risk factor for strokemodifiable risk factor for stroke

HTN contributes to 70% of all HTN contributes to 70% of all strokesstrokes Atheroma in carotids, aortic archAtheroma in carotids, aortic arch Friability of small cerebral end Friability of small cerebral end

arteriesarteries LV dysfunction and atrial fibrillationLV dysfunction and atrial fibrillation

Benefits of Treating Benefits of Treating Hypertension Hypertension

Younger than 60 yrsYounger than 60 yrs Reduces the risk of stroke by 42%Reduces the risk of stroke by 42% Reduces the risk of coronary event by 14%Reduces the risk of coronary event by 14%

Older than 60yrsOlder than 60yrs Reduces overall mortality by 20%Reduces overall mortality by 20% Reduces cardiovascular mortality by 33%Reduces cardiovascular mortality by 33% Reduces incidence of stroke by 40%Reduces incidence of stroke by 40% Reduces coronary artery disease by 15%Reduces coronary artery disease by 15%

Treat Hypertension Treat Hypertension AggressivelyAggressively

Target most patients still < 140/90Target most patients still < 140/90 Home Measurement < 135/85 Home Measurement < 135/85 Diabetics < 130/80Diabetics < 130/80

Lifestyle Modification:Lifestyle Modification: Sodium restriction, DASH diet, physical Sodium restriction, DASH diet, physical

activity, weight loss, alcohol restriction, activity, weight loss, alcohol restriction, smoking cessationsmoking cessation

Expect to use combination therapyExpect to use combination therapy ACE inhibitor, ARB, diureticACE inhibitor, ARB, diuretic

Per

cent

(%

)

Hypertension outcome trials

Kjeldsen et al. Blood Pressure 2001;10:190-192.

76543210

STOP-1

SHEP

STONE

SYST-EUR

SYST-CHINA

HOT

CAPP

STOP-2

NICS

NORDIL

INSIGHT

StrokeMyocardial infarction

Reference: Lancet 2001; 358: 1033-41

PROGRESS TRIALPROGRESS TRIAL

Randomised placebo-controlled Randomised placebo-controlled trial designed to determine the trial designed to determine the effects of a blood pressure-effects of a blood pressure-lowering regimen on the risks of lowering regimen on the risks of stroke and other major vascular stroke and other major vascular events in hypertensive and non events in hypertensive and non hypertensive patients with a hypertensive patients with a history of stroke or TIAhistory of stroke or TIA

Reference: Lancet 2001; 358: 1033-41

Pro

po

rtio

n w

ith

ev

ent

Placebo

Active*

0 1 2 3 4Follow-up time (years)

28% risk reduction95% CI 17 - 38%

p<0.0001

*Active: perindopril 4 mg ± indapamide

PROGRESS TRIAL PROGRESS TRIAL STROKE RISK STROKE RISK REDUCTIONREDUCTION

0.00

0.05

0.10

0.15

0.20

Hypertension: ARB Hypertension: ARB StudiesStudies

• LIFE LIFE (Losartan Intervention for Endpoint Reduction in Hypertension)(Losartan Intervention for Endpoint Reduction in Hypertension)

• Randomized controlled trialRandomized controlled trial• Treatment:Treatment:

• Losartan + Atenelol placebo Losartan + Atenelol placebo vsvs Atenelol + Losartan placebo Atenelol + Losartan placebo • Hydrochlorothiazide added at 2 monthsHydrochlorothiazide added at 2 months• At 4 months - Losarten or Atenelol doubled to achieve target BP At 4 months - Losarten or Atenelol doubled to achieve target BP

< 140/90 < 140/90• ResultsResults

• More patients reached target BP with Losarten vs Atenelol armMore patients reached target BP with Losarten vs Atenelol arm• 25% decrease incidence of diabetes25% decrease incidence of diabetes• Less incidence of stroke, MI and death in Losarten armLess incidence of stroke, MI and death in Losarten arm

Lancet 2002;359:995-1003Lancet 2002;359:995-1003

LIFE: Fatal/Nonfatal LIFE: Fatal/Nonfatal StrokeStroke

Losartan

Atenolol

Adjusted Risk Reduction 24·9%, p=0·001Unadjusted Risk Reduction 25·8%, p=0.0006

Pro

po

rtio

n o

f p

atie

nts

wit

h f

irst

eve

nt

(%)

0

1

2

3

4

5

6

7

8

B Dahlof et al. Lancet 2002;359:995-1003

0 6 12 18 24 30 36 42 48 54 60 66

Study Month

Treatment of Treatment of HypertensionHypertension

withwith Cerebrovascular Cerebrovascular DiseaseDisease• Strongly consider blood pressure reductionStrongly consider blood pressure reduction

in all patients in all patients after the acute phase after the acute phase of non of non disabling stroke or TIAdisabling stroke or TIA

• Recommended agents:Recommended agents:ACE-I, diureticsACE-I, diureticsARB - ongoing studiesARB - ongoing studiesß-blockers, CCBß-blockers, CCB

Hypercholesterolemia: Hypercholesterolemia: Using Statins for Using Statins for

Secondary Prevention of Secondary Prevention of StrokeStroke

Lipid-lowering trials using Lipid-lowering trials using statinsstatins have shown benefit in decreasing have shown benefit in decreasing progression and/or inducing progression and/or inducing regression of carotid artery plaqueregression of carotid artery plaque

Lipid-lowering trials using Lipid-lowering trials using statinsstatins for for secondary prevention (of CHD) have secondary prevention (of CHD) have shown benefit in stroke preventionshown benefit in stroke prevention

Why Should Statins Why Should Statins Prevent Ischemic Stroke?Prevent Ischemic Stroke?

Lipid effects = LDL loweringLipid effects = LDL lowering Target LDL-C < 2.0 mmol/L (in stroke Target LDL-C < 2.0 mmol/L (in stroke

patients)patients)

Non-lipid effects = Non-lipid effects = Stabilizing plaquesStabilizing plaques Improving endothelial functionImproving endothelial function Decreasing inflammationDecreasing inflammation Decreasing platelet aggregationDecreasing platelet aggregation Directly lowering blood pressureDirectly lowering blood pressure Decreasing cardiac emboliDecreasing cardiac emboli

Statin StudiesStatin Studies• SPARCL SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels)(Stroke Prevention by Aggressive Reduction in Cholesterol Levels)

• Double Blind Randomized Controlled TrialDouble Blind Randomized Controlled Trial• Stroke or TIA within 1-6 monthsStroke or TIA within 1-6 months• Treatment:Treatment:

• Atorvastatin 80 mg once daily or placebo Atorvastatin 80 mg once daily or placebo • ResultsResults

• 5 year absolute reduction in risk of stroke - 22%5 year absolute reduction in risk of stroke - 22%• 5 year absolute reduction in risk of major CV events - 3.5%5 year absolute reduction in risk of major CV events - 3.5%• Significant increase in hemorrhagic strokeSignificant increase in hemorrhagic stroke

N Engl J Med 2006;355:549-559N Engl J Med 2006;355:549-559

Hypercholesterolemia: Hypercholesterolemia: Using Statins for Using Statins for

Secondary Prevention of Secondary Prevention of StrokeStroke

Should statins be used if lipids Should statins be used if lipids normal?normal?

consider statin if event presumed to consider statin if event presumed to be of atherosclerotic origin even if be of atherosclerotic origin even if no preexisting indications no preexisting indications

Stroke 2006;37:577-Stroke 2006;37:577-617617

Cholesterol Lowering-----Cholesterol Lowering-----

Statins as first line therapyStatins as first line therapy Ezetimibe: Ezetimibe:

a) First line for patients a) First line for patients intolerant to intolerant to

statinsstatins

b) Dual inhibition b) Dual inhibition

Secondary Stroke PreventionSecondary Stroke Prevention

Evaluate the EventEvaluate the Event:: Identify Events requiring Urgent intervention / Identify Events requiring Urgent intervention / Identify causeIdentify cause TIA / Minor Stroke Risk Assessment TIA / Minor Stroke Risk Assessment Investigations Investigations

CT, MRI, ECG, Carotid imaging, echocardiogramCT, MRI, ECG, Carotid imaging, echocardiogram

Implement InterventionsImplement Interventions Carotid EndarterectomyCarotid Endarterectomy

Initiate MedicationsInitiate Medications Antiplatelets /anticoagulants, ACE-I, Diuretics, ARB, Antiplatelets /anticoagulants, ACE-I, Diuretics, ARB,

statinsstatins

Modify Stroke Risk FactorsModify Stroke Risk Factors Vascular Risk FactorsVascular Risk Factors Behavioral/Lifestyle Risk Factors Behavioral/Lifestyle Risk Factors

Impact of Impact of Prevention Prevention StrategiesStrategies

Do they work ? Do they work ?

*Based on estimated 700,000 annual strokes.Gorelick PB. Arch Neurol. 1995;52:347-355.Gorelick PB. Stroke. 2002;33:862-875.

0 100,000 200,000 300,000 400,000

360,500

146,000

89,500

68,500

34,500

Number of Preventable Strokes*

Hypertension

Cholesterol

Cigarettes

Atrial Fibrillation

Heavy Alcohol Use

How Many Strokes AnnuallyHow Many Strokes AnnuallyCan Be Prevented by Risk-Factor Can Be Prevented by Risk-Factor

Control?Control?

25,000

10,000

5000

6400

2500

Cumulative Relative risk Cumulative Relative risk reductionreduction

Survivors of first stroke and a TIASurvivors of first stroke and a TIA Diet, Exercise, Aspirin, Statins and Diet, Exercise, Aspirin, Statins and

Anti-hypertensivesAnti-hypertensives RR of 80%RR of 80% NNT 5 to prevent 1 event in 5 years NNT 5 to prevent 1 event in 5 years

Stroke. June, 2007Stroke. June, 2007

BRAIN ATTACK  

STROKE CAN BE PREVENTED!