primary and secondary stroke prevention daniel ackerman, … · 3/18/2016 1 primary and secondary...

·:{iC0Fp'16ACOFP 53rd Annual Convention & Scientific Seminars

Primary and Secondary Stroke Prevention

Daniel Ackerman, MD

3/18/2016

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Primary and Secondary Stroke Prevention

Dr. Daniel Ackerman MD

Director of Stroke and Vascular Neurology

St. Luke’s University Health Network

Clinical Assistant Professor of Neurology

Lewis Katz School of Medicine at Temple University

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Disclosures

I have no financial disclosures

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Objectives

Brief review of stroke epidemiology and pathophysiology

Primary prevention of stroke– Risk Factors

– Screening

– Special populations

Secondary prevention of stroke– Understanding etiology

– Monitoring and ongoing evaluation

Stroke prevention therapy– Antiplatelet agents

– Anticoagulation

– BP/Statins/DM

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Ok…What is a stroke anyway?

Stroke, also known as a “brain attack” is the

damage resulting from an alteration in cerebral

blood flow.

87% of strokes are ischemic, 10% ICH and 3%

SAH

Stroke affects nearly 800,000 people per year

with a new stroke every 40 seconds.

It remains the 5th leading cause of death in the

US and a leading cause of long term disability.

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Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke

Statistics—2016 Update.; 2015. doi:10.1161/CIR.0000000000000350.

St. Luke’s University Health Network 2


So why is TIME = BRAIN??

Every minute that the brain is starved for blood,

2 million neurons, 14 billion synapses, and 12

Kilometers of myelinated fibers are destroyed…

Put another way, every hour the brain ages 3.6

years.

Every 30 minutes in delay to reperfusion

decreases the likelihood of a good outcome by

10%.

Several targets for neuroprotection have been

identified including inflammation, oxidative stress,

blood-brain barrier disruption, excitotoxicity,

apoptosis, autophagy…

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no effective interventionsMozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke

Statistics—2016 Update.; 2015. doi:10.1161/CIR.0000000000000350.

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A quick word on acute care

Speed is the word of the day…

IV thrombolytics remain the standard of care for

acute ischemic stroke within 4.5 hours.

Mechanical thrombectomy is now the standard of

care for those with anterior circulation proximal

occlusions within 6 hours from the last seen

normal.

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O.Y. Chernyshev et al. Neurology 2010;74:1340-1345

©2010 by Lippincott Williams & Wilkins

What about Stroke Mimics?

Total number of pts tx with IVTPA over a 4 year retrospective study 512, total

number with MRI negative 106, 14% overall thought to be Stroke Mimics and 7%

neuroimaging negative ischemia, NO cases of symptomatic ICH, NIHSS on

discharge was about 0, very limited functional disability…

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Primary Prevention

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Some of the common risk factors

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Non-Modifiable– Age

– Gender

– History of TIA/Stroke

Genetic– Hypercoaguable state

– Fabry Disease

– Sickle Cell

– Trisomy 21

– CADASIL

Modifiable– Hypertension

– Dyslipidemia

– Diabetes

– Obesity

– Obstructive Sleep Apnea

– Tobacco Use

– A-Fib

– Medication/iatrogenic

– Drug/Alcohol abuse

Meschia, J. F., et al (2014). Guidelines for the Primary Prevention of Stroke: A Statement for

Healthcare Professionals From the American Heart Association/American Stroke Association .

Stroke , 45 (12 ), 3754–3832. http://doi.org/10.1161/STR.0000000000000046


Doc…am I at risk?

No single risk assessment tool captures all of the

complexities of age, race, gender, genetics, etc…

2 Different approaches– Lumping: Combining risk factor sets based on observed

associations. Easy to use on a relatively wide scale but may

have pitfalls in generalizability.

– Splitting: Evaluating risk factors separately on a patient specific

basis. More challenging and not necessarily more accurate as

some risk factors and the association/interaction between them

may not be well defined.

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Doc…am I at risk?

No single risk assessment tool captures all of the

complexities of age, race, gender, genetics, etc…

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Started in 1948 with the recruitment of 5200

participants.

Additional cohorts have been added including the

children and grandchildren of the original group

and new additions to improve diversity.

There are questions about generalizability among

those with minimal risk factors and in people of

more diverse racial and geographic backgrounds.

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www.framinghamheartstudy.org


MEN 0 1 2 3 4 5 6 7 8 9 10

Age 54-56 57-59 60-62 63-65 66-68 69-72 73-75 76-78 79-81 82-84 85

SBP (untreated)

97-105 106-115 116-125 126-135 136-145 146-155 156-165 166-175 176-185 186-195 196-205

SBP (treated)

97-105 106-112 113-117 118-123 124-129 130-135 136-142 143-150 151-161 162-176 177-205

DM XXX

Tob XXX

CVD XXX

A-Fib XXX

LVH XXX

Variables were defined as follows: SBP, systolic blood pressure in mmHG; Diabetes, history of diabetes; Tob, smokes cigarettes; CVD

(cardiovascular disease), history of myocardiai infarction, angina pectoris, coronary insufficiency, intermittent claudication, or congestive heart

failure; AF, history of atrial fibrillation; LVH, left ventricular hypertrophy on electrocardiogram.

Prediction of 10 year probability of Stroke in Men


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Points 1 2 3 4 5 6 7 8 9 10

10-yr prob.

3% 3% 4% 4% 5% 5% 6% 7% 8% 10%

Points 11 12 13 14 15 16 17 18 19 20

10-yr prob.

11% 13% 15% 17% 20% 22% 26% 29% 33% 37%

Points 21 22 23 24 25 26 27 28 29 30

10-yr prob.

42% 47% 52% 57% 63% 68% 74% 79% 84% 88%

Prediction of 10 year probability of Stroke in Men



WOMEN 0 1 2 3 4 5 6 7 8 9 10

Age 54-56 57-59 60-62 63-64 65-67 68-70 71-73 74-76 77-78 79-81 82-84

SBP (untreated)

95-106 107-118 119-130 131-143 144-155 156-167 168-180 181-192 193-204 205-216

SBP (treated)

95-106 107-113 114-119 120-125 126-131 132-139 140-148 149-160 161-204 205-216

DM XXX

Tob XXX

CVD XXX

A-Fib XXX

LVH XXX XXX

Variables were defined as follows: SBP, systolic blood pressure in mmHG; Diabetes, history of diabetes; Tob, smokes cigarettes; CVD

(cardiovascular disease), history of myocardiai infarction, angina pectoris, coronary insufficiency, intermittent claudication, or congestive heart

failure; AF, history of atrial fibrillation; LVH, left ventricular hypertrophy on electrocardiogram.

Prediction of 10 year probability of Stroke in Women



Points 1 2 3 4 5 6 7 8 9 10

10-yr prob.

1% 1% 2% 2% 2% 3% 4% 4% 5% 6%

Points 11 12 13 14 15 16 17 18 19 20

10-yr prob.

8% 9% 11% 13% 16% 19% 23% 27% 32% 37%

Points 21 22 23 24 25 26 27

10-yr prob.

43% 50% 57% 64% 71% 78% 84%

Prediction of 10 year probability of Stroke in Women


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St. Luke’s University Health Network 19http://my.americanheart. org/cvriskcalculator



http://my.americanheart. org/cvriskcalculator

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More specific screening tools may be available

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Some more specific populations are challenging

in terms of general guidelines and risk tools.– Specific ethnic/racial considerations

– Local cultural effects

– Theoretical risks

Pubmed search for “primary stroke prevention”

limiting results to review papers published in the

last 5 years yields 554 results.


Patient specific risk

Age

Low Birth Weight

Race/Ethnicity

Physical Inactivity

Dyslipidemia

Hypertension

Obesity

Diabetes

Tobacco

Atrial Fibrillation

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Established cardiac disease

Carotid artery stenosis

(asymptomatic)

Migraine with aura

Alcohol use/abuse

Drug Abuse

Sleep disordered breathing

Hyperhomocysteinemia

Inflammation/infection

Meschia, J. F. et al (2014). Guidelines for the Primary Prevention of Stroke: A

Statement for Healthcare Professionals From the American Heart

Association/American Stroke Association . Stroke , 45 (12 ), 3754–3832.

Kernan, W. N. et al (2014). Guidelines for the Prevention of Stroke in Patients With

Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From

the American Heart Association/American Stroke Association . Stroke , 45 (7 ),


Carotid Artery Disease…whom do we screen?

The risk for stroke in an asymptomatic carotid disease

(CAD) is not as high as symptomatic CAD but knowing

who to screen is challenging.

The prevalence of severe asymptomatic carotid stenosis

in the US population is estimated at 3.1%

There is clearly a subset of people who are at higher

risk…

The AHA/ASA recommends screening with doppler

ultrasound for select patients with bruits, symptomatic

PVD or coronary disease, or >/= 2 atherosclerotic risk

factors

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Genetic Risk

Family History:– Those with a parent who suffered a stroke under age 65 were at

3X higher risk of stroke

Conditions associated with increased risk– Sickle Cell Disease

– Trisomy 21

– Fabry Disease

– MELAS

– CADASIL

– Intrinsic hypercoaguable state

– Autosomal dominant polycystic kidney disease

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Ok…I’ve had a stroke, so now what?

A brief word on recovery

Etiology is key to understanding secondary

prevention.

Ongoing monitoring

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Stroke Recovery

Requires a multidisciplinary effort and

takes…TIME (6-12 months or more).

May be complicated by loss of independence and

several changes in lifestyle.

Anxiety and depression are major common

barriers.

Education and re-education followed by

education and support… and then some

education.

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Common types/causes of ischemic stroke

Embolic– Cardioembolic

• Structure problem

• Rhythm problem

• Hypercoaguable state

– Atheroembolic (artery to artery)

– Septic

– Other (air, Onyx, fat)

Thrombotic– Small vessel ischemic disease

Hypoperfusion– Watershed area

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But he’s so healthy at home…

Frequently a stroke is the bridge to reveal

vascular risk.

Post stroke evaluation typically includes– Brain structure imaging (preferably Brain MRI without contrast)

– Vascular imaging

– Echocardiography

– Fasting lipid panel

– Diabetes evaluation

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Extra’s that may be necessary

Long term heart rhythm monitoring– Holter vs. ILR

Hypercoaugable evaluation

Vasculitis evaluation– Primary Angiitis of the CNS

– Secondary vasculitis/vasculopathy

Inflammatory state/autoimmune disease

Drug and Alcohol use

Pregnancy test

OSA evaluation

In spite of all this, about 30% of strokes remain

cryptogenic.

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What about that drug I saw on TV?

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Treatment Options:

Antiplatelet agents

Anticoagulation

BP control

Lipid-lowering agents

Glycemic control

Surgical revascularization

Lifestyle modification program

OSA tx

Other*

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Antiplatelet agents

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http://www.australianprescriber.com/magazine/30/4/92/6/ with modification


Antiplatelet agents

Aspirin– For primary prevention in those with 10 year risk >10%, may also

be considered in those with CKD (GFR between 30-45); unclear

if it is helpful in those with DM and low 10 year CVD risk.

– For patients with a bio-prosthetic heart valve

– Initial agent for secondary prevention without extenuating

circumstances (allergy, severe CKD, PUD, etc…)

Cilostazol– For primary prevention in those with peripheral arterial disease

Clopidogrel– May be considered for secondary prevention in patients who fail

aspirin therapy

– Need to consider hypo/non-responders

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Antiplatelet FAQ’s and Controversies

What about Aggrenox?– Reasonable for secondary stroke prevention but not often used.

Doses of Aspirin– There have not been any studies demonstrating a difference

between 81mg and 325mg for stroke prevention at this point.

Dual antiplatelet agents– One study suggested a benefit for secondary prevention when

initiated early but it was only done in China and has limited

generalizability.

– May be considered for those with severe intracranial

atherosclerosis, recent drug-eluting stent placement, or with

atrial fibrillation who cannot tolerate anticoagulants.

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Oral anticoagulants

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http://www.slideshare.net/peraltalorca1/804185-slide


Oral anticoagulants

Anticoagulation– Non-valvular A-Fib with Chads2Vasc >/= 2

– Mitral valve stenosis and an embolic event or left atrial thrombus

– Those with heart failure (EF </ 30%) and an embolic event

– Potentially those with a hypercoaguable state

– Evaluation for those with Cryptogenic stroke and ESUS is ongoing

Warfarin– Primary or secondary prevention in valvular A-fib and those with

mechanical aortic or mitral valves (typically with ASA 81mg)

* The addition of an antiplatelet agent is not recommended except in cases of

clinically apparent coronary artery disease/ACS or stent placement.

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Obligatory NOAC comparison slide

Name Dabigatran Apixaban Rivaroxaban Edoxaban

Target Factor II Factor Xa Factor Xa Factor Xa

Schedule BID BID Daily Daily

Reversal Hemodialysis, Idarucizumab

PCC’s/non-specific



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Hypertension

Represents the most important modifiable risk

factor.

For primary prevention, annual screening of

those with prehypertension with lifestyle

modification is recommended.

Effect of treatment is more important than the

specific agent considered.

The target for BP reduction is uncertain but goal

values <140/90 are reasonable. In some

circumstances SBP < 130 may be desirable.

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Dyslipidemia

Rather than a specific LDL target, for primary

prevention, low/moderate/high intensity statin

therapy is recommended for

low/intermediate/high risk as determined by the

AHA/ASA risk calculator.

Other agents may help lower cholesterol but are

not proven to help reduce the incidence of stroke.

For secondary prevention, when a stroke is

presumed to be atherosclerotic, high intensity

statin is recommended; even if LDL < 100.

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Stone NJ, et al. 2013 ACC/AHA guideline on the

treatment of blood cholesterol to reduce atherosclerotic

cardiovascular risk in adults: A report of the american

college of cardiology/american heart association task

force on practice guidelines. Circulation. 2014;129(25

SUPPL. 1).

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Statin Therapy

Low Intensity Daily dose lowers LDL-C by >30%

Simvastatin 10mgPravastatin 10-20mgLovastatin 20mgFluvastatin 20-40mgPitavastatin 1mg

Moderate Intensity Daily dose lowers LDL-C by approximately 30-50%

Atorvastatin 10-20mgRosuvastatin 5-10mgSimvastatin 20-40mgPravastatin 20-40mgLovastatin 40mgFluvastatin XL 80mgFluvastatin 40mg BIDPitavastatin 2-4mg

High Intensity Daily dose lowers LDL-C by >/=50%

Atorvastatin 40-80mgRosuvastatin 20-40mg

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Diabetes

For those with DM and otherwise low CV risk the

benefit of aspirin for primary prophylaxis is

unclear.

Patients with stroke/tia should be evaluated for

DM, HgB A1c is likely more accurate in the early

acute setting.

There are not guidelines from the AHA/ASA that

are specific for stroke but we typically counsel for

a goal HgB A1c <7%.

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Surgical intervention

Intracranial:– Angioplasty and/or stenting is considered investigational and

should only be considered in the case of failure of medical

therapy.

Carotid revascularization:– May consider CEA in asymptomatic patients with >70% stenosis

if the risk of perioperative MI/stroke/death is <3%. CAS may be

considered in this setting but effectiveness compared to best

medical management is not clear.

– Consider CEA or CAS in symptomatic patients with >70%

stenosis by non-invasive imaging or > 50% by cath based

imaging (or non-invasive imaging with corroboration) as long as

periprocedural expected stroke/death rate is <6%.

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Lifestyle Modification

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Sleep disordered breathing

Represents a modifiable risk factor for

cardiovascular disease and stroke.

Would be reasonable to evaluate with forms such

as the Epworth sleepiness scale or via referral to

a sleep center/polysomnography.

Is among the interventions for stroke prevention

that will really help the patient feel better.

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Potpouri

Cerebral Amyloid Angiopathy– Boston Criteria

Aortic arch atheroma

Sickle Cell disease– Transfuse to a goal of HgB S < 30%

Migraine with aura– Consider avoiding contraceptives and counsel strongly to avoid

tobacco use.

Pregnancy

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Summary

Stroke is ubiquitous, rapid, and unforgiving.

The best offense is a good defense.

Partnering with your local vascular neurologist

can help to clarify complex cases.

THANK YOU FOR YOUR ATTENTION!

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primary and secondary stroke prevention daniel ackerman, … · 3/18/2016 1 primary and secondary...

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