secondary prevention slide set: aha stroke guideline 2006
TRANSCRIPT
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Guidelines for Prevention ofStroke in Patients with
Ischemic Stroke or TransientIschemic Attack From theStroke Council of the AHA
Ralph L. Sacco, Chair; Robert Adams, Vice-Chair
Greg Albers, Mark J. Alberts, Oscar Benavente, Karen Furie, Larry B.Goldstein, Philip Gorelick, Jonathan Halperin, Robert Harbaugh, S.
Claiborne Johnston, Irene Katzan, Margaret Kelly-Hayes, Edgar J.
Kenton, Michael Marks, Lee H. Schwamm, Thomas Tomsick
Stroke 2006;37:577-617
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Presentation Compiled by the
AHA/ASA Professional
Education Committee
Susan C. Fagan, Chair
Deborah Bergman
Glenn D. Graham
S. Claiborne Johnston
Karen Johnston
Edgar J. KentonDawn Kleindorfer
Creed Pettigrew
Kathryn Taubert, Staff Scientist
Karen Modesitt, Staff
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Introduction
This slide set was adapted from the AHA/ASA
Guidelines for Prevention of Stroke in Patients withIschemic Stroke or Transient Ischemic Attack.
From the American Heart Association/American
Stroke Association Council on Stroke
Co-Sponsored by the Council on Cardiovascular
Radiology and Intervention
Affirmed by the American Academy of Neurology
The full-text guidelines are available on the Web site
of the AHA (www.americanheart.org)
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Introduction
Since the 1999 AHA Stroke Council guidelines
for the secondary prevention of stroke, important
evidence from clinical trials has emerged that
further supports and broadens the options foraggressive risk reduction therapies.
The secondary prevention patient population to
be addressed includes those with prior stroke or
transient ischemic attack, regardless of etiology.
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Changes from 1999 Guidelines
1999 guidelines* DID NOT include levels ofevidence
BP targets have been lowered to 120/80
For diabetes, HbA1c
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Changes from 1999 Guidelines
Antiplatelet agents now the sole antithrombotic
recommended for noncardioembolic stroke
Aspirin no longer solely recommended as first line Ticlopidine no longer recommended as an option
New guidelines much more comprehensive
Wolf PA et al. Stroke 1999;30:1991-94
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Secondary Prevention Definition
Therapy to reduce recurrent stroke and other
cardiovascular events and decrease cardiovascular
mortality in patients with previous stroke or TIA.
Although prevention of stroke is of primary
interest, many grades of recommendations were
chosen to reflect the existing evidence on the
reduction of all cardiovascular outcomes.
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Transient Ischemic Attacks
Guidelines now recognize TIA as an important
harbinger of stroke.
- >10% 90-day risk of stroke after TIA
Prevention recommendations for patients with
ischemic stroke are now broadly applied to
those with TIA.
- Recognizes common etiologies and urgentneed for treatment
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AHA Classes and Levels of Evidence
Class I Agreement the treatment is useful and effective
Class II Conflicting evidence and/or a divergence of opinion about
the usefulness/efficacy of a treatment.
- Class IIa Weight of evidence is in favor of the treatment.
- Class IIb Usefulness/efficacy is less well established by evidence
Class III Evidence and/or general agreement that the treatment is
not useful/effective and in some cases may be harmful.
Levels of Evidence
A: Data derived from multiple randomized trials. B: Data derived from a single randomized trial or nonrandomized
studies.
C: Consensus opinion of experts.
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Components of Secondary
Prevention
Diuretics +/- ACE inhibitors
Statins
Antiplatelet agents / anticoagulants
Blood pressure control
Diabetes management
Lipid management
Smoking cessation
Alcohol moderationWeight reduction / physical activity
Carotid artery Interventions
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Challenges of Dissemination
The committee acknowledges that strategies forimplementation of the guidelines need to be
developed and disparities in health care delivery
addressed.
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Blood Pressure Control
ASA 2006 Secondary Stroke Recs Antihypertensivesare recommended beyond thehyperacute period (Class I, Evidence A).
- Benefit for those with & w/o HTN (Class IIa,
Evidence B)
- Target BP level and reduction are uncertain, butnormal BP levels are
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PROGRESS Trial Results
Combination versus Monotherapy
Events
active placebo
Favorsactive
Favorsplacebo
RiskReduction
(95%CI)
Stroke
Combination 150/1770 255/1774 43% (30 to 54)
Single Drug 157/1281 165/1280 5% (-19 to 23)
Total Stroke 307/3051 420/3054 28% (17 to 38)
0.4 1.0 2.0
Hazard Ratio
PROGRESS Collaborative Group. Lancet 2001;358:1033-41
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PROGRESS Trial Results
Hypertensive versus Normotensive Patients
Events/patients
Active Placebo
Favors
active
Favors
placebo
Risk reduction
(95%CI)
Stroke
Hypertensive 163/1464 235/1452
Non-hypertensive 144/1587 185/1602
Total stroke 307/3051 420/3054
Major vascular events
Hypertensive 240/1464 331/1452
Non-hypertensive 218/1587 273/1602
Total events 458/3051 604/3054
32% (17 to 44)
27% (8 to 42)
28% (17 to 38)
29% (16 to 40)
24% (9 to 37)
26% (16 to 34)
0.5 1.0 2.0Hazard ratio
PROGRESS Collaborative Group. Lancet 2001;358:1033-41
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Diabetes
ASA 2006 Secondary Stroke Recs
More rigorous control of HTN and dyslipidemia
should be considered in patients with DM.
- BP targets of 130/80 mm Hg (Class IIa,
Evidence B). ACEIs and ARBs are recommended asfirst-choice medications for patients with DM (Class
I, Evidence A).
Glucose control is recommended to near
normoglycemic levels to reduce microvascular
complications (Class I, Evidence A) and possibly
macrovascular complications (Class IIb, Evidence B).
Hemoglobin A1c goal
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Those with elevated chol, CHD, or evidence of an
atherosclerotic origin should be managed according
to NCEP III* (Class I, Evidence A).
Statins are recommended with target LDL-C of
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Cholesterol Control
ASA 2006 Secondary Stroke Recs
Baselinefeature SIMVASTATIN(10269)PLACEBO(10267)
Rate ratio & 95% CISTATIN better PLACEBO better
Prior coronary disease
Yes
No
1459 1841(21.8%) (27.5%)
574 744(16.1%) (20.8%)
Prior cerebrovascular disease
Yes 406 488(24.7%) (29.8%)
No 1627 2097(18.9%) (24.3%)
Prior diabetes
Yes 601 748(20.2%) (25.1%)
No 1432 1837(19.6%) (25.2%)
ALL PATIENTS 2033 2585(19.8%) (25.2%)
0.4 0.6 0.8 1.0 1.2 1.4
24% SE 3reduction(2P
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HPS: Conclusions for people with
cerebrovascular disease
Lowering LDL cholesterol by 1 mmol/L (40 mg/dL)reduces the 5-year risk of ischemic stroke by about one
quarter, with no apparent adverse effect on cerebral
hemorrhage.
Similar proportional reductions in stroke risk are seen
with statin therapy irrespective of age, sex, lipid levels,
blood pressure, or use of other medications (including
aspirin).
Statin therapy clearly reduces the risk of major vascular
events among people with pre-existing cerebrovascular
disease, irrespective of the presence of coronary disease.
Heart Protection Study Collaborative Group. Lancet 2002;360:7-22
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Recommendations for Modifiable
Behavioral Risk Factors
Smoking: All ischemic stroke or TIA patients whosmoked in the past should be encouraged not to smoke
(Class I, Level C).
Alcohol: Patients with prior ischemic stroke or TIA who
are heavy drinkers should eliminate or reduce their
consumption of alcohol (Class I, Level A).
Obesity: Weight reduction may be considered for all
overweight ischemic stroke or TIA patients to maintain thegoal BMI (Class IIb, Level C).
Physical activity: Substantial evidence exists that physical
activity exerts a beneficial effect on multiple cardiovascular
risk factors including those for stroke (Class IIB, Level C).
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Symptomatic Carotid
Endarterectomy ASA 2006
Secondary Stroke Recs Ipsilateral severe (70% to 99%) carotid stenosis,
CEA is recommended (Class I, Evidence A).
Ipsilateral moderate (50% to 69%) carotidstenosis, CEA is recommended depending on age,
gender, comorbidities, and the severity of symptoms
(Class I, Evidence A).
Stenosis
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Urgent Endarterectomy
Surgery within 2 weeks is suggested rather than delaying surgery
(Class IIa, Evidence B).
Rothwell PM. Lancet 2004;363(9413):915-24
C tid A i l t d St ti
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Carotid Angioplasty and Stenting
ASA 2006 Secondary Stroke Recs
CAS may be considered (Class IIb, Evidence B).- Stenosis (>70%) difficult to access surgically
- Medical conditions that greatly increase the
risk for surgery, or
- When other circumstances exist such as
radiation-induced stenosis or restenosis after
CEA.
CAS is reasonable when performed by operatorswith morbidity and mortality rates of 4% to
6% (Class IIa, Evidence B).
At i l Fib ill ti
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Atrial Fibrillation
ASA 2006 Recommendations
For patients with ischemic stroke or TIA with
persistent or paroxysmal (intermittent) AF,
anticoagulation with adjusted-dose warfarin (target
INR 2.5, range 2.0 to 3.0) is recommended (Class I,Evidence A).
For patients unable to take oral anticoagulants,
aspirin 325 mg per day is recommended (Class I,Evidence A).
Stroke Prevention:
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Stroke Prevention:
Non-cardioembolic
ASA 2006 RecommendationsFor patients with noncardioembolic ischemic
stroke or TIA, antiplatelet agents are
recommended rather than oral anticoagulationto reduce the risk of recurrent stroke and other
cardiovascular events (Class I, Evidence A).
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Warfarin-Aspirin for Recurrent
Stroke Study (WARSS)
9009329519749841004103210571103Aspirin
885924939956972998101310471103Warfarin
No. at Risk
0 90 180 270 360 450 540 630 720
Days After Randomization
0
10
20
30
Probabilityof
Event(%)
Warfarin
Aspirin
1.13Hazard Ratio
P=0.25
The primary
outcome occurred
in 17.8% of
patients in the
warfarin group and
16.0% in the ASA
group.
Mohr JP et al. N Engl J Med 2001;345:1444-51
tro e revent on: on car oem o c
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tro e revent on: on-car oem o c
ASA 2006 Recommendations
Acceptable options for initial therapy
(Class IIa, Evidence A).
- aspirin (50-325 mg qd)
- the combination of aspirin and extended-release dipyridamole (25/200 mg bid)
- clopidogrel (75 mg qd)
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Antiplatelet Therapy
ASA 2006 Recommendations
Compared to aspirin alone, both the
combination of aspirin and extended-release
dipyridamole and clopidogrel are safe.
The combination ofaspirin and extended-release
dipyridamole is suggested instead of aspirin alone
(Class IIa, Level A).
Clopidogrel is suggested instead of aspirin alone
based on direct comparison trials
(Class IIb, Level B).
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ESPS 2: Effects on StrokeRelative
Risk Reduction (Pair-wise Comparisons)
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
30.0%
35.0%
40.0%37.0%
P< 0.001
16.3%P= 0.039
18.1%P= 0.013
23.1%
P= 0.006
ER-DP = Extended-Release
Dipyridamole
ASA = Acetylsalicylic Acid
RRR = Relative Risk Reduction
RRR
ASA/ER-DP vs. Placebo
ER-DP vs. Placebo
ASA vs. Placebo
ASA/ER-DP vs. ASA
ESPS 2 Group. J Neurol Sci 1997;151(suppl):S1-S77
CAPRIE Study
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Efficacy of Clopidogrel vs Aspirin in MI,
Ischemic Stroke, or Vascular Death (n=19,185)
CAPRIE Study
Months of Follow-up
C
u mu
la t i
ve E
ve n t R
a te
( %)
0
4
8
12
16
ClopidogrelClopidogrel
AspirinAspirinOverall
Relative RiskReduction
8.7%*
3 6 9 12 15 18 21 24 27 30 33 36
AspirinAspirin
5.83%5.83%
5.32%5.32%
ClopidogrelClopidogrel
Event Rate per YearEvent Rate per Year
*ITT analysis.CAPRIE Steering Committee. Lancet 1996;348:1329-39
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Secondary Stroke Prevention
ASA 2006 Recommendations
Insufficient data are available to make evidence-
based recommendations regarding choices between
antiplatelet options other than aspirin. Selection of
an antiplatelet agent should be individualized based
on patient risk factor profiles, tolerance, and other
clinical characteristics.
S S i
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Secondary Stroke Prevention
ASA 2006 Recommendations
The addition of aspirin to clopidogrel increases
the risk of hemorrhage and is not routinely
recommended for stroke or TIA patients (ClassIII, Evidence A).
For patients allergic to aspirin, clopidogrel is
recommended (Class IIa, Evidence B).
MATCH T i l P i E d P i t
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MATCH Trial Primary End Point:MI, IS, Vascular Death, or Rehospitalization for an Acute
Ischemic Event
OverallRelative Risk
Reduction
6.4%*
P
= 0.244
*ITT Analysis
CumulativeEven
tRate
Clopidogrel+ ASA
Clopidogrel+ Placebo
0.00
0.04
0.08
0.12
0.16
0.20
0 3 6 9 12 15 18
N=7,599
Months of Follow Up
Diener H-C et al. Lancet 2004;364:331-7
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MATCH: Safety Outcomes
Excess life-threatening bleeding events withcombination versus clopidogrel monotherapy:
96 (2.6%) vs. 49 (1.3%); p
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Secondary Stroke Prevention
ASA 2006 Recommendations
For patients who have an ischemic
cerebrovascular event while taking aspirin,
there is no reliable evidence that increasing the
dose of aspirin provides additional benefit.Although alternative antiplatelet agents are
often considered for these patients, no single
agent or combination has been specifically
evaluated in patients who have had an event
while receiving aspirin.
St k d P
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Stroke and Pregnancy
ASA 2006 Secondary Stroke Recs
High-risk thromboembolic conditions consider:- adjusted-dose UFH throughout pregnancy,
- adjusted-dose LMWH with Factor Xa
monitoring
- UFH or LMWH until week 13, followed bywarfarin until mid-3rd trimester, then UFH or
LMWH in last trimester (Class IIb,
Evidence C).
Lower risk conditions
- UFH or LMWH in the first trimester followed
by - low-dose aspirin for the remainder of the
pregnancy (Class IIb, Evidence C).
Adj t d R l ti Ri k f St k
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Adjusted Relative Risk of Stroke
According to a Womans Status With
Respect to Pregnancy*
* Relative risks have been adjusted for age and race; The 6-week period after pregnancy was defined as the 6 weeks after aspontaneous or induced abortion, stillbirth, or live birth;
Subarachnoid hemorrhages (SAHs) have been excluded.
During pregnancy or 6 weeks 1.6 (1.0-2.7) 5.6(3.0-10.5) 2.4 (1.6-3.6)
After pregnancy
During pregnancy 0.7 (0.3-1.6) 2.5 (1.0-6.4) 1.1(0.6-2.0)
During 6 weeks after pregnancy 5.4 (2.9-10.0)18.2(8.7-38.1) 7.9 (5.0-12.7)
After delivery 8.7 (4.6-16.7)28.3 (13.0-61.4)12.7 (7.8-20.7)
After abortion 1.1 (0.2-7.9) 4.5 (0.6-33.1) 1.8
RR of RR of RRof Cerebral Intracerebral EitherType Infarction Hemorrhage of
Stroke
Risk Period (95% CI) (95% CI) (95%CI)
Kittner SJ et al. (1996), N Engl J Med 335(11):768-774
P t l H
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Postmenopausal Hormones
ASA 2006 Secondary Stroke Recs
For women with ischemic stroke or TIA,
postmenopausal hormone therapy (with estrogen
with or without a progestin) is not recommended(Class III, Evidence A).
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Womens Health Initiative
16,608 postmenopausal women, 50-79 years,with an intact uterus at baseline were recruited
by 40 U.S. clinical centers for the period 1993-
1998.
Received conjugated equine estrogens, 0.625
mg/d, plus medroxyprogesterone acetate, 2.5
mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).
After a mean of 5.2 years of follow-up, the trialwas stopped because of high rates of invasive
breast cancer and the global index statistic
supported risks exceeding benefits.
Rossouw et al. JAMA 2002;288(3):321-33
Estimates of Cumulative Hazards for
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Estimates of Cumulative Hazards for
Strokes in Womens Health Initiative
Study
Time (Years)
Cumulative
Hazard
0.030
0.025
0.020
0 1 2 3 4 5 6 7
0.015
0.010
0.005
0
Estrogen +
Progestin
Placebo
Rossouw et al. JAMA 2002;288(3):321-33
Other Circumstances
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Other Circumstances
ASA 2006 Secondary Stroke Recs
Dissections
PFO and hyperhomocysteinemia
Hypercoagulable states
Sickle cell disease
Cerebral venous thrombosis
Anticoagulation after cerebral hemorrhage
L l A R d i
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Level A Recommendations
Antihypertensive treatment
Glucose control to reduce microvascular
complications of diabetes
Statins to reduce LDL to
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Summary
These guidelines provide comprehensive andtimely evidence-based recommendations.
There is an intent to fully update the guidelines
every 3 years, with updates encouraged when
pivotal studies are published.