Effective Secondary Stroke Prevention VHA -------------------------------- Marilyn M.Rymer, MD Saint Luke’s Brain and Stroke Institute Howard Kirshner,

Effective Secondary Stroke Prevention

VHA --------------------------------Marilyn M.Rymer, MD

Saint Luke’s Brain and Stroke InstituteHoward Kirshner, MD

Vanderbilt University Medical Center-----------------------------------------------

Section 1

•   Examine the epidemiology and pathophysiology for the occurrence of transient ischemic stroke (TIA) and of secondary strokes, including appropriate diagnostic evaluation to determine cause

A TIA – What is it?

• Classical definition: A neurological deficit lasting <24 hours due to focal ischemia of the brain or retina.

• Newer thinking: A brief episode of neurological dysfunction caused by focal brain or retinal ischemia with clinical symptoms lasting < 1 hour and without evidence of acute infarction

• TIA is “angina of the brain”, a medical emergency• 30-50% of TIA patients have an infarct by DWI (stroke,

not TIA)• 10% have a stroke in upcoming weeks, half in 48 hours• NSA Guidelines: admit, evaluate, treat

Prognosis After TIA1,707 patients identified by ED MDs with TIA among 16 hospitals

in HMO in northern California; follow-up to 90 days

Johnston SC, et al. JAMA. 2000;284:2901-2906.

Stroke 10.5%

Adverse Events 25.1% (stroke, cardiovascular hospitalization, death, or recurrent TIA)

No. of Pts. at Risk

Stroke 1,001 1,577 1,527 1,480 1,451AE 1,001 1,462 1,361 1,293 1,248

Stroke Risk and ABCD2 ScoreOxfordshire TIA Study

Symptom ScoreMaximum score is 7. Score 6 or 7 = high risk

AAge ≥60 years 1 point

BBlood pressure ≥140/90 mm Hg 1 point

CClinical features [of TIA]2 points for unilateral weakness1 point for speech impairment without weakness

DDuration [of TIA]2 points for ≥60 minutes1 point for 10-59 minutes

DDiabetes 1 point 7-day stroke risk was 8.5-10.5%

Risk of stroke before appointment correlated with ABCD2>4 Johnston SC, et al. Lancet. 2007;369:283-292.

Stroke Risk by ABCD Score

0% 0%

2%1% 1%

3%4%

6%

10%

8%

12%

18%

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

0-1 2-3 4-5 6-7

2 Day Risk7 Day Risk90 Day Risk

EXPRESS Study Effect of urgent treatment of TIA and minor

stroke on early recurrent stroke: A prospective population-based sequential comparison

•Background – Risk of recurrent stroke is as high as 10% in the week following TIA•Study Objective – Prospectively determine the effect on process of care and outcome after TIA/minor stroke of more urgent assessment and treatment•Primary Outcome – 1278 patients in the UK with TIA or minor stroke•Risk of stroke within 90 days following TIA/minor stroke

Rothwell PM, et al, Lancet. 2007;370:1432-1442.Rothwell PM, et al, Lancet. 2007;370:1432-1442.

EXPRESS Results

Rothwell PM, et al, Lancet. 2007;370:1432-1442.

N = 1278 Phase 1 Phase 2

P = 0.0001

Phase I-Usual care: rate of stroke 10.3%Phase II-Urgent care: rate of stroke 2.1% (p<.0001)

MRI Diffusion Study

The first step in secondary prevention is to try to find the cause

of the stroke or TIA

Stroke SubtypesIschemic Stroke (83%)Ischemic Stroke (83%)Hemorrhagic Stroke (17%)Hemorrhagic Stroke (17%)

AtherothromboticAtherothromboticCerebrovascularCerebrovascularDisease Disease (20%)(20%)

Embolism Embolism (20%)(20%)Lacunar Lacunar (25%)(25%)Small vessel diseaseSmall vessel disease

Cryptogenic and Cryptogenic and Other KnownOther KnownCause Cause (30%)(30%)

IntracerebralIntracerebralHemorrhage Hemorrhage (59%)(59%)

Subarachnoid Hemorrhage Subarachnoid Hemorrhage (41%)(41%)

Albers GW, et al. Chest. 1998;114:683S-698S.Rosamond WD, et al. Stroke. 1999;30:736-743.

Large Vessel Aortic Atherosclerosis

Large vessel carotid artery disease causing thrombosis or embolism

Lenticulostriate small vesselsSite of lacunar strokes

Posterior CirculationPenetrating small vessel branches

off the basilar artery

Evaluation of the Vascular System

Reprinted with permission from Albers GW, et al. Chest. 2001;119:300S-320S.

Penetrating arterydisease

Flow-reducingcarotid stenosis

Atrial fibrillation

Valve disease

Left ventricularthrombi

Cardiogenicemboli

Aortic archplaque

Carotid plaque witharteriogenic emboli

Intracranialatherosclerosis

Stroke Diagnostic TestsBrain imaging: CT, MRCardiac Imaging: TTE, TEE, heart

monitoringLipid, coagulation testingVascular Imaging:Noninvasive

MR angiography (MRA) Intracranial, extracranial

CT angiography (CTA) Intracranial, extracranial

Ultrasound: Carotid, TCD

Invasive Conventional cerebral angiography

Image courtesy of Regional Neurosciences Unit, Newcastle General Hospital, Newcastle, UK.

MRI Head MRA Head

Baseline ImagingBaseline Imaging

Section 2

• Identify the risk factors leading to secondary stroke, following an initial TIA or stroke

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

360,500

146,000

89,500

68,500

34,500

Number of Preventable Strokes Per Year*

Hypertension

Cholesterol

Cigarettes

Atrial Fibrillation

Heavy Alcohol Use

How Many Strokes in the US Can Be Prevented Per Year by Risk-Factor

Control?

*Based on estimated 700,000 annual strokes.

Gorelick PB. Arch Neurol. 1995;52:347-355.Gorelick PB. Stroke. 2002;33:862-875.

JNC-7 Recommendations forBlood Pressure Control

BP

Class

SBP*

mm Hg

DBP*

mm Hg

Lifestyle Modification

Initial Drug Therapy

No Compelling Indication

With Compelling Indications

Normal <120 and <80 Encourage

Pre-HTN 120-139 or 80-90 Yes Not indicated For compelling indications‡

Stage 1 HTN

140-159 or 90-99 Yes THZ diuretic for most. May consider ACEI, ARB, BB, CCB or combination

Drugs for the compelling indications. Other anti-HTN drugs as needed (diuretics, ACEI, ARB, BB, CCB)

Stage 2 HTN

160 or 100 Yes Two-drug comb for most†

*Treatment determined by highest BP category.†With caution in those with orthostatic hypotension.‡Chronic kidney disease or diabetes: BP goal <130/80 mm Hg.Chobanian AV, et al. Hypertension. 2003;42:1206-1252.

HOPE Study: 32% Reduction in Stroke Risk

The HOPE Study Investigators. N Engl J Med. 2000;342:145-153.

-35

-30-25

-20-15

-10-5

0

26%

CV Death

NonfatalMIStroke

32%

20%16%

All-CauseMortality*

• Aspirin and other antiplatelets• Beta-blockers• Lipid-lowering agents

Ramipril’s Benefit Beyond Standard Risk-Reduction Therapies Alone

• Diuretics• Calcium channel blockers

% R

ela

tive

Ris

k R

edu

ctio

n

Composite Outcome

22%P=0.0001

P=0.0002

P=0.0002

P=0.0003P=0.005

*Secondary end point

Pro

po

rtio

n w

ith

ev

ent

95% CI 17 - 38%

P<0.0001Placebo

Active (perindopril+ indapamide)

0.20

0.15

0.10

0.05

0.000 1 2 3 4 (Years)

28% RR

PROGRESS TrialStroke Risk Reduction

All participants

PROGRESS Collaborative Group. Lancet 2001; 358: 1033-41

Diabetes and Stroke• Patients with diabetes require more

rigorous control of blood pressure (<130/80 mm Hg) and blood lipids (LDL < 100)

• Tight glycemic control can reduce microvascular disease and other end points, such as neuropathy

.

Adapted from Sacco RL, et al. Stroke. 2006;37:577-617.

Statins for Stroke Prevention: Why?

• Stroke patients are at high risk of cardiovascular events

• Statin therapy reduces: – The risk of stroke after MI1-3

– The risk of stroke or death after carotid endarterectomy4

• The FDA has approved several statin agents for patients with “stroke or evidence of cerebrovascular disease”

1. Sacks FM, et al. N Engl J Med. 1996;335:1001-1009.2. The LIPID Study Group. N Engl J Med. 1998;339:1349-1357. 3. Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.4. Kennedy J, et al. Stroke. 2005;36:2072-2076.

SPARCL Results: Primary End Point

First occurrence of fatal or nonfatal stroke

The SPARCL Investigators. N Engl J Med. 2006;355:549-559.

16

12

10

8

00 1 2 3 4 5 6

Fat

al o

r N

on

fata

l Str

oke

(%

) Placebo

Atorvastatin

HR, 0.84 (95% CI, 0.71-0.99); P=.03

No. At Risk

Atorvastatin 2365 2208 2106 2031 1935 922 126

Placebo 2366 2213 2115 2010 1926 887 137

Years Since Randomization

SPARCL Trial: Results

End Point RR, %

(atorvastatin vs placebo)

P value

Stroke or TIA ↓23 .001

Major coronary event ↓35 .003

Major CVD events ↓20 .002

Any cardiovascular event ↓42 .001

Revascularization ↓45 .001

Hemorrhagic stroke 1.66-fold increase

The SPARCL Investigators. N Engl J Med. 2006;355:549-559.

SMOKING CESSATION

• It helps to recommend it

• 5 years after stopping smoking, stroke risk back to non-smoker’s

• Behavioral therapy• Rx: Zyban, patches,

Chantix

• Section 3

• Assess the latest information on risk factor control for recurrent strokes, especially carotid artery disease and cardioembolism

Absolute Benefits of Carotid Endarterectomy (CEA)

CEA had marginal benefits on annual rates of ipsilateral stroke for patients with asymptomatic or moderate lesions. Dramatic benefit was seen for high-grade, symptomatic stenoses.

Nicolaides AN, et al. Eur J Vasc Endovasc Surg. 2005;30:275-284.

Stents and Angioplasty• SAPPHIRE: Carotid stent + angioplasty with

protection device in high risk surgical patients. 50% stenosis in symptomatic; 80% in asymptomatic. Results=5.8% stroke, MI, death in stent group; 12.5% surgical group at 30 days; recent 3 year follow-up, no difference

• Vertebral stents: anecdotal good outcomes• Intracranial stents: considered investigational

Carotid Stents

• CREST: NIH multicenter trial CEA vs stent with protection in symptomatic and asymptomatic patients with >50% stenosis (still enrolling)

Carotid Stent

Carotid stent

When to Stent While CREST is Pending

• Recommend for patients with symptomatic >70% stenosis in whom stenosis is difficult to access surgically, medical conditions increase surgical risk, or special circumstances such as radiation-induced stenosis or restenosis after CEA.

• Vertebral stents: symptomatic patients who fail medical therapy

• Intracranial stents: still investigational

Intracranial Stenosis

• WASID TRIAL: ASA vs warfarin in intracranial ICA, MCA, vertebral, basilar symptomatic stenoses– No difference in combined death and stroke– More deaths and bleeding in warfarin group– Conclusion: ASA is the treatment of choice– SAMMPRIS trial- stent vs ASA, underway

LEFTLEFT

MCAMCA

STENOSISTENOSISS

Cardioembolism

• Atrial fibrillation: >2M cases in the US resulting in 75,000 strokes annually

• Advanced age, CHF, diabetes, prior stroke increase risk is people with AF.

• Recommend warfarin with INR 2-3 (target 2.5)

Warfarin in Prospective NVAF Trials

Intention-to-treat AnalysisS

tro

ke r

ate

(% /

year

)

Adapted from Atwood JE, et al. Herz. 1993;18:27-38.

8

6

4

2

0AFASAK SPAF BAATAF CAFA SPINAF

825 504 922 490 896 p=0.03 p=0.01 p=0.002 p>0.2 p=0.001

person-yearsp value

Control

Warfarin

4.6

1.9

7.0

2.33.0

0.4

3.6

2.1

4.3

0.9

NVAF – nonvalvular atrial fibrillation

Adapted from Hersi A, et al. Curr Probl Cardiol. 2005;30:175-233.

Score 0 = low risk Score 0 = low risk ASA onlyASA only

Score 1-2 = Score 1-2 = intermediate riskintermediate riskASA or warfarinASA or warfarin

Score 3-6 = high Score 3-6 = high risk warfarinrisk warfarin

Score 0 = low risk Score 0 = low risk ASA onlyASA only

Score 1-2 = Score 1-2 = intermediate riskintermediate riskASA or warfarinASA or warfarin

Score 3-6 = high Score 3-6 = high risk warfarinrisk warfarin

CHADS2 Stroke Risk Stratification Scheme for Patients With NVAF

Risk Factors ScoreC Recent congestive heart failure 1H Hypertension 1A Age ≥75 years 1D Diabetes mellitus 1S2 History of stroke or transient ischemic attack 2

Connolly S. et al. Lancet. 2006;367:1903-1912

Number at Risk C+A 3,335 3,149 2,387916OAC 3,371 3,220 2,453911

0.00

0.02

0.04

0.06

0.08

0.10

0.0 0.5 1.0 1.5

Years

Cu

mu

lati

ve H

aza

rd R

ate

s

3.93 %/year

5.64 %/yearRR = 1.45

p=0.0002

OAC

Clopidogrel+ASA

OAC – oral anticoagulation

ACTIVE W Trial: Primary Efficacy Outcome: Stroke, Non-CNS Systemic Embolism, MI &

Vascular Death

Active W=The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events" Active W=The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events"

PARADOXICAL EMBOLISM

• Small clots in leg or pelvic veins – generally not seen on venous ultrasound studies

• Usually no sign of thrombophlebitis• Sudden change in intrathoracic pressure i.e.

valsalva (scuba divers at risk)• Clot travels from right atrium to left atrium via

PFO with potential for cerebral embolism• Evaluate for hypercoagulability

SHOULD THE PFO BE SHOULD THE PFO BE CLOSED?CLOSED?

(vs antiplatelet, (vs antiplatelet, anticoagulation?)anticoagulation?)

When to use warfarin in stroke?(Red Clot vs White Clot)

• Atrial fibrillation and related cardiac sources of embolism

• PFO/Atrial septal aneurysm (?)

• Venous sinus thrombosis• Hypercoagulable states

(APL antibody (??)• Carotid, vertebral

dissections (?)• Intracranial stenosis (X)

• “Treatment failures” (X)

Section 4

• Determine from evidence the role of antithrombotic agents in the prevention and treatment of secondary stroke

Warfarin Aspirin Recurrent Stroke Study (WARSS)

• 2200 ischemic, non A Fib stroke patients • > 50% small vessel• Warfarin INR 1.4-2.8 v. ASA 325 mg• No difference in stroke (trend favored ASA)• Slight trend favoring warfarin in “cryptogenic” • No difference: anticardiolipin Ab, PFO• Warfarin: limited indications in stroke Mohr J, et al, for the WARSS Group. N Engl J Med. 2001;345:1444-1451

Warfarin-Aspirin for Recurrent Stroke Study (WARSS)

0 90 180 270 360 450 540 630 720

Days after Randomization

Aspirin

Warfarin

Pro

bab

ilit

y o

f Even

t (%

)

30

20

10

0

Number at RiskWarfarin 1103 1047 1013 998 972 956 939 924 885

Aspirin 1103 1057 1032 1004 984 974 951 932 900Mohr J, et al, for the WARSS Group. N Engl J Med. 2001;345:1444-1451

Antiplatelet Therapy

Antiplatelet Trialists’ Collaboration. BMJ. 1994;308(6921):81-106.

OtherHigh Risk

32%32%

Antiplatelet TherapyControl

% o

f P

atie

nts

Hav

ing

Str

oke

, MI,

or

Vas

cula

r D

eath

PriorStroke/TIA

Acute MI Prior MI HighRisk

0%

5%

10%

15%

20%

25%22%22%

29%29%

25%25%

25%25%27%27%

AllPatients

3PLA012c

Efficacy of Antiplatelets in Preventionof Ischemic Events

ESPS 2: Effects on Stroke–RRR(Pairwise Comparisons)

ESPS 2 Group. J Neurol Sci. 1997;151(suppl):S1-S77.

37.0%P < .001

16.3%P =.039

18.1%P =.013

23.1%P =.006

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

30.0%

32.0%

40.0%

RRR

ASA/ER-DP vs Placebo

ER-DP vs Placebo

ASA vs Placebo

ASA/ER-DP vs ASA

ESPRIT Trial

• 3 groups of patients with TIA or minor stroke: ASA, ASA + DP, warfarin

• Reported outcomes of 1376 pts with ASA alone, 1363 pts with ASA + DP

• 1o events in 173 (13%) of ASA + DP, 216 of ASA (16%); hazard .80 (.66-98), ARR 1% per year (1.1-1.8)

• Bleeding essentially equal• Dropout 34% ASA + DP, 14% ASA• Meta-analysis of ASA + DP trials: hazard .82

(.74-.91)

ESPRIT Study Group. Lancet. 2006;367:1665-1673.

Efficacy of Clopidogrel vs. Aspirin in MI, Stroke, or Vascular Death (n= 19,185)

Months of Follow-UpMonths of Follow-Up

Cu

mu

lati

ve

Cu

mu

lati

ve

Ev

ent

Ra

te (

%)

Ev

ent

Ra

te (

%)

00

44

88

1212

1616

ClopidogrelClopidogrel

AspirinAspirinOverall Overall

Relative RiskRelative RiskReductionReduction

8.7%*8.7%*

00 33 66 99 1212 1515 1818 2121 2424 2727 3030 3333 3636

AspirinAspirin

5.83%5.83%

5.32%5.32%

ClopidogrelClopidogrel

Event Rate per YearEvent Rate per Year

P P = 0.045= 0.045

*ITT analysis.CAPRIE Steering Committee. Lancet 1996;348:1329-1339.

MATCH: Management of Atherothrombosis With Clopidogrel

in High-Risk PatientsPatient population 7599 patients with

– Recent TIA or ischemic stroke (within 3 months) and

– High-risk recurrent ischemic events

Study drugs Clopidogrel 75 mg/d Aspirin + Clopidogrel 75 mg/d

Treatment duration Up to 18 months

MATCH = Management of atherothrombosis with clopidogrel in high-risk patients withrecent transient ischemic attack or ischemic stroke.

Diener HC, et al. Lancet. 2004;364;331-337.

RRR: 6.4% (P=.244)

ASA + Clopidogrel

Placebo + Clopidogrel

IS, MI, VD, rehospitalization for acute ischemic event

Cu

mu

lati

ve e

ven

t ra

te

0.00

0.04

0.08

0.12

0.16

0.20

Months of follow-up

0 3 6 9 12 15 18

MATCH: Primary End Point

Diener H-C. Antiplatelet therapy: results of the MATCH trial. Paper presented at: European Stroke Conference;

May 13, 2004; Mannheim-Heidelberg, Germany.

MATCH: Life-Threatening and Major

Bleeding

Diener HC, et al. Lancet. 2004;364;331-337.

2.5%

1.3%

1.9%

0.6%

P <.0001

P <.0001

0

1

2

3

4

5

Placebo +Clopidogrel

Aspirin + Clopidogrel

Ble

edin

g E

ven

ts (

%)

Major

Life-threatening

CHARISMA: Study Design

Clopidogrel 75 mg Clopidogrel 75 mg ++

ASA 75–162 mgASA 75–162 mgn=7802n=7802

Placebo +Placebo +ASA 75–162 mgASA 75–162 mg

n=7801n=7801

Symptomatic patients Symptomatic patients with coronary, with coronary,

cerebrovascular, or cerebrovascular, or peripheral arterial peripheral arterial

disease*disease*n=12,153 n=12,153

Follow-up until 1040 primary Follow-up until 1040 primary eventsevents

Primary end point:Primary end point:First occurrence of MI, stroke (any cause), CV death (including First occurrence of MI, stroke (any cause), CV death (including

hemorrhagic)hemorrhagic)Principal secondary end point:Principal secondary end point:

First occurrence of MI, stroke, CV death, hospitalization for UA, TIA, First occurrence of MI, stroke, CV death, hospitalization for UA, TIA, revascularizationrevascularization††

Randomized,double-blind

Asymptomatic patients Asymptomatic patients with multiple with multiple

atherothrombotic atherothrombotic risk factors*risk factors*

n=3284 n=3284

N=15,603

*n=166 not in either category, but included in overall analysis.†Coronary, cerebral, or peripheral. CHARISMA=Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management,and Avoidance. Bhatt DL et al. N Engl J Med. 2006;354:1706-1717.

Population n RR (95% CI)P Value

Documented CV disease 12,153 0.88 (0.77, 0.998) .046

Coronary 5835 0.86 (0.71, 1.05) .13

Cerebrovascular 4320 0.80 (0.65, 0.997) .05

PAD 2838 0.87 (0.67, 1.13) .29

Multiple risk factors 3284 1.20 (0.91, 1.59) .20

Overall population 15,603 0.93 (0.83, 1.05) .22

CHARISMA: Primary Efficacy Results (MI/Stroke/CV Death)* by Inclusion Criteria

0.6 0.8 1.41.2Clopidogrel betterPlacebo better

1.60.4

*First occurrence of MI (fatal or nonfatal), stroke (fatal or nonfatal), or CV death.Bhatt DL. Presented at: American College of Cardiology Annual Scientific Session; March 11-14, 2006, Atlanta, GA.Bhatt DL, et al. N Engl J Med. 2006;354:1706-1717.

CHARISMA: Safety End Points by Inclusion Criteria

Event Rate (%)

P ValueClopidogrel

+ ASAPlacebo + ASA

Symptomatic

Severe bleeding*

Moderate bleeding*

1.6

2.1

1.4

1.3

.39

<.001

Asymptomatic

Severe bleeding*

Moderate bleeding*

2.0

2.2

1.2

1.4

.07

.08

*Bleeding was defined using GUSTO criteria.GUSTO=Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

Bhatt DL et al. N Engl J Med. 2006;354:1706-1717.

Antiplatelet Therapy in Stroke Prevention: PRoFESS Study Design

(Recruitment ended 5/06, Results at ESC 5/08)

ER-DP/ASA Clopidogrel

Telmisartan

ER-DP/ASA+

telmisartan(n=3875)

Clopidogrel+

telmisartan(n=3875)

n=10,000

Placebo

ER-DP/ASA +

placebo (n=3875)

Clopidogrel +

placebo(n=3875)

n=10,000

n=10,000 n=10,000 N=20,000

On June 4, 2004, the PRoFESS Steering Committee discontinued the ASA component of the clopidogrel + ASA treatment arm after release of the MATCH trial data showed no benefit for combination therapy.PRoFESS=Prevention Regimen for Effectively Avoiding Second Strokes.Available at: http://www.clinicaltrials.gov/ct/show/NCT00153062?order=1. Accessed March 31, 2006.

PRoFESS: Primary Efficacy Outcome

ER-DP + ASA

Clopido-grel

Hazard Ratio

(95% Confidence

Interval) P Value

First recurrent stroke

9.0% 8.8% 1.01 (0.92-1.11)

0.783

Recurrent ischemic stroke

7.7% 7.9%

Hemorrhagic stroke

0.8% 0.4%

Sacco R. European Stroke Conference Webcast. Available at http://eurostroke.org. Accessed May 15, 2008.

PRoFESS: Secondary Efficacy Outcome

ER-DP + ASA

Clopido-

grel

Hazard Ratio (95%

Confidence Interval) P Value

Stroke, MI, or vascular death

13.1% 13.1% 0.99 (0.92-1.07)

0.83

Boehringer Ingelheim. Available at: http://www.boehringer-ingelheim.com. Accessed May 14, 2008.

AHA/ASA RecommendationsAntiplatelet Therapy

• Noncardioembolic ischemic stroke/ TIA antiplatelet agents recommended, rather than oral anticoagulants (I,A)

• ASA, ASA/ER dipyridamole, and clopidogrel all acceptable for initial therapy (IIa, A)

• ASA/ER dipyridamole suggested over ASA alone (IIb, A)• Clopidogrel may be considered over ASA alone (IIb, B)• ASA + clopidogrel not routinely recommended for

ischemic stroke/TIA (III, A)• Clopidogrel is reasonable for patients with ASA allergy

(IIa, B) .

AHA/ASA Council on Stroke. Stroke. 2006;37:577-617.

Get With The Guidelines—Stroke

Performance Indicator Baseline GWTG

Antithrombotics at discharge* 91.0% 97.6%

Anticoagulation for atrial fibrillation at discharge* 81.4% 97.6%

Therapy at discharge if LDL >100 mg/dL or on therapy at admit*

58.7% 81.6%

Counseling for smoking cessation* 38.8% 83.8%

Lifestyle changes recommended for BMI >25 kg/m2 33.7% 42.3%

Fonarow GC. The first million patients in the Get With The Guidelines program:lessons learned. http://www.cardiosource.com/editorials/index.asp?EdID=101. Accessed March 12, 2008.

Performance on Selected Treatment and Quality of Care Indicators for Acute Stroke and Secondary Prevention (cont)

*Indicates 1 of the 7 key performance measures targeted in GWTG-Stroke.

Data collected from 141,449 clinically identified patients admitted to 778 hospitals participating in the GWTG-Stroke program from January 1, 2006, through December 31, 2006.

Conclusions• Ischemic stroke is a major cause of mortality and

disability in the United States• Most strokes could be prevented by risk factor

Rx: diet, exercise, smoking cessation, BP, lipid Rx; important also for secondary prevention

• Carotid endarterectomy, stenting • Anticoagulation for atrial fib, related disorders• Antiplatelet therapy for all but warfarin-indicated

patients; ASA, ASA-ER dipyridamole, clopidogrel

• New guidelines for secondary stroke prevention updated in 1/08