Secondary Prevention Slide Set: AHA Stroke Guideline 2006

8/14/2019 Secondary Prevention Slide Set: AHA Stroke Guideline 2006

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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


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


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


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


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


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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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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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


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


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


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.

Secondary Prevention Slide Set: AHA Stroke Guideline 2006

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