Effective Secondary Stroke
Prevention
VHA -------------------------------Marilyn M.Rymer, MD
Saint Luke’s Brain and Stroke Institute
Howard 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 TIA
1,707 patients identified by ED MDs with TIA among 16 hospitals
in HMO in northern California; follow-up to 90 days
Stroke 10.5%
Adverse Events 25.1%
(stroke, cardiovascular
hospitalization, death, or recurrent TIA)
No. of
Pts. at Risk
Stroke
AE
1,001
1,001
1,577
1,462
1,527
1,361
Johnston SC, et al. JAMA. 2000;284:2901-2906.
1,480
1,293
1,451
1,248
Stroke Risk and ABCD2 Score
Oxfordshire TIA Study
Symptom
Score
Maximum score is 7. Score 6 or 7 = high
risk
Age ≥60 years
1 point
Blood pressure ≥140/90 mm Hg 1 point
Clinical features [of TIA]
2 points for unilateral weakness
1 point for speech impairment without
weakness
Duration [of TIA]
2 points for ≥60 minutes
1 point for 10-59 minutes
Diabetes
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
18%
18%
16%
14%
2 Day Risk
7 Day Risk
90 Day Risk
12%
12%
10%
10%
8%
8%
6%
6%
4%
4%
3%
2%
2%
0%
1% 1%
0% 0%
0-1
2-3
4-5
6-7
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.
EXPRESS Results
Phase I-Usual care: rate of stroke 10.3%
Phase II-Urgent care: rate of stroke 2.1% (p<.0001)
Phase 1
Phase 2
N = 1278
Risk of Recurrence (%)
12
10
8
6
4
2
0
10
20
30
40
50
60
Time (days)
70
80
90
P = 0.0001
Rothwell PM, et al, Lancet. 2007;370:1432-1442.
MRI Diffusion Study
The first step in secondary
prevention is to try to find the cause
of the stroke or TIA
Stroke Subtypes
Hemorrhagic Stroke (17%)
Intracerebral
Hemorrhage (59%)
Ischemic Stroke (83%)
Atherothrombotic
Cerebrovascular
Disease (20%)
Cryptogenic and
Other Known
Cause (30%)
Subarachnoid Hemorrhage (41%)
Lacunar (25%)
Embolism (20%)
Small vessel disease
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 vessels
Site of lacunar strokes
Posterior Circulation
Penetrating small vessel branches
off the basilar artery
Evaluation of the Vascular System
Intracranial
atherosclerosis
Carotid plaque with
arteriogenic emboli
Aortic arch
plaque
Cardiogenic
emboli
Penetrating artery
disease
Flow-reducing
carotid stenosis
Atrial fibrillation
Valve disease
Left ventricular
thrombi
Reprinted with permission from Albers GW, et al. Chest. 2001;119:300S-320S.
Stroke Diagnostic Tests
Brain imaging: CT, MR
Cardiac Imaging: TTE, TEE, heart
monitoring
Lipid, coagulation testing
Vascular 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.
Baseline Imaging
MRI Head
MRA Head
Section 2
• Identify the risk factors leading to
secondary stroke, following an initial TIA or
stroke
How Many Strokes in the US Can Be
Prevented Per Year by Risk-Factor
Control?
Hypertension
360,500
Cholesterol
146,000
Cigarettes
89,500
Atrial Fibrillation
68,500
34,500
Heavy Alcohol Use
0
100,000
200,000
300,000
400,000
Number of Preventable Strokes Per Year*
*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 for
Blood Pressure Control
Initial Drug Therapy
BP
Class
SBP*
mm Hg
DBP*
mm Hg
Lifestyle
Modification
<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
Stage 2
HTN
160
or 100
Yes
Two-drug comb
for most†
Drugs for the
compelling
indications. Other
anti-HTN drugs as
needed (diuretics,
ACEI, ARB, BB,
CCB)
Normal
No Compelling
Indication
*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.
With Compelling
Indications
HOPE Study: 32% Reduction
in Stroke Risk
Ramipril’s Benefit Beyond Standard Risk-Reduction Therapies Alone
% Relative Risk Reduction
• Aspirin and other antiplatelets
• Beta-blockers
• Lipid-lowering agents
0
-5
-10
-15
-20
-25
-30
-35
Composite
Outcome
Stroke
• Diuretics
• Calcium channel blockers
CV
Death
Nonfatal
MI
All-Cause
Mortality*
16%
20%
22%
P=0.005
P=0.0003
26%
P=0.0001
32%
P=0.0002
P=0.0002
The HOPE Study Investigators. N Engl J Med. 2000;342:145-153.
*Secondary end
point
PROGRESS Trial
Stroke Risk Reduction
All participants
28% RR
0.20
Proportion with event
95% CI 17 - 38%
P<0.0001
0.15
Placebo
Active (perindopril
+ indapamide)
0.10
0.05
0.00
0
1
2
PROGRESS Collaborative Group. Lancet 2001; 358: 1033-41
3
4
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
Fatal or Nonfatal Stroke (%)

16
Placebo
12
Atorvastatin
10
8
HR, 0.84 (95% CI, 0.71-0.99); P=.03
0
0
1
2
3
4
5
6
Years Since Randomization
No. At Risk
Atorvastatin 2365
2208
2106
2031
1935
922
126
Placebo
2213
2115
2010
1926
887
137
2366
The SPARCL Investigators. N Engl J Med. 2006;355:549-559.
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
LEFT
MCA
STENOSIS
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 Analysis
8
Control
7.0
Stroke rate (% / year)
Warfarin
6
4.6
4.3
3.6
4
2
1.9
2.3
3.0
2.1
0.9
0.4
0
person-years
p value
AFASAK
825
p=0.03
SPAF
504
BAATAF
922
CAFA
490
SPINAF
896
p=0.01
p=0.002
p>0.2
p=0.001
NVAF – nonvalvular atrial fibrillation
Adapted from Atwood JE, et al. Herz. 1993;18:27-38.
CHADS2 Stroke Risk Stratification
Scheme for Patients With NVAF
Risk Factors
C
H
A
D
S2
Score
Recent congestive heart failure
Hypertension
Age ≥75 years
Diabetes mellitus
History of stroke or transient ischemic attack
1
1
1
1
2
Score 0 = low risk
ASA only
Score 1-2 =
intermediate risk
ASA or warfarin
Score 3-6 = high
risk warfarin
Adapted from Hersi A, et al. Curr Probl Cardiol. 2005;30:175-233.
ACTIVE W Trial: Primary Efficacy Outcome:
Stroke, Non-CNS Systemic Embolism, MI &
Vascular Death
0.10
5.64 %/year
Cumulative Hazard Rates
RR = 1.45
0.08
p=0.0002
0.06
Clopidogrel+ASA
3.93 %/year
0.04
OAC
0.02
0.00
Number
at Risk
C+A
OAC
0.0
0.5
1.0
1.5
2,387
2,453
916
911
Years
3,335
3,371
3,149
3,220
Active W=The Atrial Fibrillation Clopidogrel Trial with Irbesartan
for Prevention of Vascular Events"
Connolly S. et al. Lancet. 2006;367:1903-1912
OAC – oral anticoagulation
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 CLOSED?
(vs antiplatelet, 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
Probability of Event (%)
Warfarin-Aspirin for Recurrent
Stroke Study (WARSS)
30
20
Warfarin
10
Aspirin
0
0
Number at Risk
Warfarin
Aspirin
90 180 270 360 450 540 630 720
Days after Randomization
1103 1047 1013 998
972
956
939
924
885
1103 1057 1032 1004 984
974
951
932
900
Mohr J, et al, for the WARSS Group. N Engl J Med. 2001;345:1444-1451
Antiplatelet Therapy
% of Patients Having
Stroke, MI, or Vascular Death
Efficacy of Antiplatelets in Prevention
of Ischemic Events
25%
22%
Antiplatelet Therapy
Control
25%
20%
29%
27%
25%
15%
32%
10%
5%
0%
Prior
Acute MI
Stroke/TIA
Prior MI
Other
High Risk
High
Risk
All
Patients
Antiplatelet Trialists’ Collaboration. BMJ. 1994;308(6921):81-106.
3PLA012c
ESPS 2: Effects on Stroke–RRR
(Pairwise Comparisons)
40.0%
37.0%
P < .001
32.0%
30.0%
25.0%
20.0%
16.3%
P =.039
18.1%
P =.013
23.1%
P =.006
ASA/ER-DP vs Placebo
ER-DP vs Placebo
15.0%
ASA vs Placebo
10.0%
ASA/ER-DP vs ASA
5.0%
0.0%
RRR
ESPS 2 Group. J Neurol Sci. 1997;151(suppl):S1-S77.
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)
Event Rate per Year
Aspirin
Aspirin
Clopidogrel
16
12
5.83%
5.32%
8
Clopidogrel
4
P = 0.045
0
0
3
6
9 12 15 18 21 24 27 30 33 36
Months of Follow-Up
*ITT analysis.
CAPRIE Steering Committee. Lancet 1996;348:1329-1339.
8.7%*
Overall
Relative Risk
Reduction
MATCH: Management of
Atherothrombosis With Clopidogrel
in High-Risk Patients
Patient 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 with
recent transient ischemic attack or ischemic stroke.
Diener HC, et al. Lancet. 2004;364;331-337.
MATCH: Primary End Point
IS, MI, VD, rehospitalization for acute ischemic event
0.20
Cumulative event rate
Placebo + Clopidogrel
0.16
ASA + Clopidogrel
RRR: 6.4%
0.12
(P=.244)
0.08
0.04
0.00
0
3
6
9
12
15
18
Months of follow-up
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
Bleeding Events (%)
5
4
1.9%
3
Major
Life-threatening
P <.0001
2
0.6%
1
P <.0001
2.5%
1.3%
0
Placebo +
Clopidogrel
Diener HC, et al. Lancet. 2004;364;331-337.
Aspirin + Clopidogrel
CHARISMA: Study Design
N=15,603
Symptomatic patients with
coronary, cerebrovascular, or
peripheral arterial disease*
n=12,153
Clopidogrel 75 mg +
ASA 75–162 mg
n=7802
Asymptomatic patients with
multiple atherothrombotic
risk factors*
n=3284
Randomized,
double-blind
Placebo +
ASA 75–162 mg
n=7801
Follow-up until 1040 primary events
Primary end point:
First occurrence of MI, stroke (any cause), CV death (including hemorrhagic)
Principal secondary end point:
First occurrence of MI, stroke, CV death, hospitalization for UA, TIA, revascularization†
*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.
CHARISMA: Primary Efficacy Results
(MI/Stroke/CV Death)* by Inclusion Criteria
Population
n
Documented CV disease
12,153
RR (95% CI)
P Value
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
3284
1.20 (0.91, 1.59)
.20
15,603
0.93 (0.83, 1.05)
.22
Multiple risk factors
Overall population
0.4 0.6 0.8
Clopidogrel better
1.2 1.4 1.6
Placebo better
*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 (%)
Clopidogrel
+ ASA
Placebo
+ ASA
P Value
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
Hazard Ratio
(95%
Clopid Confidence
o-grel
Interval)
First recurrent
stroke
9.0%
8.8% 1.01 (0.921.11)
Recurrent
ischemic stroke
7.7%
7.9%
Hemorrhagic
stroke
0.8%
0.4%
P Value
0.783
Sacco R. European Stroke Conference Webcast. Available at http://eurostroke.org. Accessed May 15, 2008.
PRoFESS:
Secondary Efficacy Outcome
Stroke, MI, or
vascular death
ER-DP +
ASA
Clopidogrel
13.1%
13.1%
Hazard Ratio
(95%
Confidence
Interval)
0.99 (0.921.07)
Boehringer Ingelheim. Available at: http://www.boehringer-ingelheim.com. Accessed May 14, 2008.
P Value
0.83
AHA/ASA Recommendations
Antiplatelet 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 on Selected Treatment and Quality of Care
Indicators for Acute Stroke and Secondary Prevention (cont)
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%
*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.
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.
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