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STROKE PREVENTION

- behind the scene -


World Stroke Day
26 October 2019
EKA HOSPITAL BSD
INTRODUCTION
RISK FACTORS AND MECHANISMS
INTERVENTIONS
SUMMARY AND RECOMMENDATIONS
Introduction

• Although there has been substantial improvement in


atherosclerotic ischemic stroke and other ASCVD outcomes in
recent decades, stroke remains the leading cause of morbidity
and mortality globally.

• Much of this is attributable to suboptimal implementation of


prevention strategies and uncontrolled ASCVD risk factors in
many adults

3
• The most important way to prevent ASCVD is to promote a healthy lifestyle
throughout life. Prevention strategies must include a strong focus on lifestyle
optimization (improvements in diet, physical activity, and avoidance of smoking)
to minimize the risk of future ASCVD events.

• A comprehensive patient-centered approach that addresses all aspects of a


patient’s lifestyle habits and estimated risk of a future ASCVD event is the first
step in deciding on where there may be a need for pharmacotherapy.

• Only when a person’s risk is sufficiently high should medications to reduce ASCVD
risk be considered as part of a shared decision-making process for optimal
treatment.
Stroke modifiable risk factors
Ten potentially modifiable risk factors account for 90% of the
population attributable risks of stroke:
hypertension,
regular physical activity,
dyslipidemia,
diet,
obesity,
psychosocial factors,
smoking,
cardiac causes,
alcohol consumption, and
diabetes mellitus
Up to 75 percent of this burden may be reduced by both
therapeutic lifestyle changes (TLCs) and adjunctive drug
therapies of proven benefit.
Yusuf S, et al. Lancet 2004;336:937-
INTRODUCTION
RISK FACTORS AND MECHANISMS
INTERVENTIONS
SUMMARY AND RECOMMENDATIONS
The major modifiable risk factors for stroke

Hypertension
Diabetes mellitus
Smoking
Dyslipidemia
Physical inactivity
Important risk factors amenable to
effective secondary prevention

Atrial fibrillation
Carotid artery stenosis

15
Important but unmodifiable risk factors

Older age, particularly age >80 years


Race and ethnicity, with risk higher for blacks than for
whites
Sex – men > women; except age 35 to 44 years and
>85 years, where women ≥ men
Family history and genetic disorders
Hypertension
Hypertension, which promotes the formation of atherosclerotic
lesions, is the single most important treatable risk factor for
stroke.
There is a gradually increasing incidence of cardiovascular
mortality as the blood pressure rises above 110/75 mmHg.
Associated with an increased likelihood of subclinical or silent
stroke → elevated risk of vascular dementia and recurrent
stroke.
Stroke risk may be associated with other blood pressure
variables including mean blood pressure, pulse pressure, blood
pressure variability, blood pressure instability, and nocturnal
nondipping.
Copyrights apply
Smoking
Increased risk for all stroke subtypes and has a strong, dose-response
relationship for both ischemic stroke and subarachnoid hemorrhage.
In the Nurses' Health Study - smokers had a relative risk of stroke of 2.58
compared with never smokers .
In the Framingham Heart Study, the odds ratio for moderate carotid stenosis
was 1.08 for each five pack-years of smoking.
Among 10,938 normotensive subjects in a prospective Swedish cohort study,
about 39 percent of strokes were attributable to smoking.
The elevated risk of stroke due to smoking declines after quitting and
is eliminated by five years later.
American Heart Association/American Stroke Association (AHA/ASA)
guidelines recommend smoking cessation for patients with stroke or
transient ischemic attack who have smoked in the year prior to the
event and suggest avoidance of environmental tobacco smoke.
Diabetes Mellitus
DM patients have approximately twice the risk of ischemic
stroke compared with those without diabetes.
The risk of stroke associated with DM is higher in women
than in men.
RF that promote carotid atherosclerosis in diabetics:
Dyslipidemia,
Endothelial dysfunction, and
Platelet and coagulation abnormalities
Impaired glucose tolerance may be a risk factor for ischemic
stroke in patients with a history of transient ischemic attack
(TIA) or minor ischemic stroke.
Dyslipidemia
Cholesterol is an established risk factor for atherosclerosis, but the
degree of risk varies for stroke subtypes.
Weak but positive association of elevated cholesterol with ischemic
stroke, particularly for large artery atherosclerotic and lacunar stroke
subtypes
An inverse association of cholesterol levels with hemorrhagic stroke.
Strong association between cholesterol and carotid atherosclerosis
also supports the role of cholesterol in the pathogenesis of large
artery ischemic stroke.
Statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9
(PCSK9) inhibitors have been shown to reduce the risk of adverse
cardiovascular events.
Among these three, statins are the best studied and have proven efficacy for
reducing the risk of recurrent ischemic stroke.
Dyslipidemia in Indonesia

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RISKESDAS 2013
Physical Inactivity
Low physical activity and prolonged sitting increases
the risk of cardiovascular disease, including stroke.
Studies showing the benefit of increased physical
activity and exercise for reducing the risk of
cardiovascular events.
Copyrights apply
Atrial Fibrillation
The most common cause of cardioembolic ischemic
stroke
Amenable to effective secondary prevention with
anticoagulation
Large and small vessel disease
The risk of ischemic stroke due to symptomatic carotid
artery stenosis can be effectively treated with
revascularization combined with intensive medical
management.
The mainstay of secondary prevention of large and
small vessel ischemic stroke or TIA is intensive medical
management including treatment with:
antiplatelet agents,
antihypertensive drugs,
statins, and
lifestyle modification
Metabolic Syndrome
Defined by the presence of three or more of the following:
abdominal obesity,
hypertriglycerides ≥150 mg/dL,
high-density lipoprotein (HDL) <40 mg/dL in men or <50 mg/dL in
women,
systolic blood pressure ≥130 mmHg or diastolic blood pressure
≥85,
fasting glucose ≥100 mg/dL.
A 10-year risk of a first CHD event of 16 to 18 percent,
which is as high as many individuals who have already had
an MI or stroke.
Considered to be a prediabetic condition linked to
increased risk of cardiovascular disease.
INTRODUCTION
RISK FACTORS AND MECHANISMS
INTERVENTIONS
SUMMARY AND RECOMMENDATIONS
INTERVENTIONS
Patients with an ischemic stroke or transient ischemic attack
(TIA) should be treated with all available risk reduction
strategies.
Currently viable strategies include:
blood pressure reduction,
statin therapy,
antithrombotic therapy,
lifestyle modification,
select patients with symptomatic carotid disease may benefit from
revascularization.
Treatment of all major stroke risk factors, compared with no
treatment, would reduce the risk of recurrent stroke by 80 %.
Antihypertensive therapy
In accordance with American Heart Association/American Stroke
Association (AHA/ASA) guidelines 2014:
resumption of antihypertensive therapy for previously treated patients with
known hypertension for both prevention of recurrent stroke and prevention
of other vascular events.
initiation of antihypertensive therapy for patients with any type of ischemic
stroke or TIA who have an established blood pressure ≥140 mmHg systolic or
≥90 mmHg diastolic.
Unlike the 2014 AHA/ASA guidelines, there is a suggestion (a weaker
recommendation) to initiateof antihypertensive therapy for previously
untreated patients with ischemic stroke or TIA of atherothrombotic, lacunar
(small vessel occlusive), or cryptogenic type, whose baseline blood pressure
is >120 mmHg systolic or >70 mmHg diastolic.
Do not give antihypertensive therapy for nonhypertensive patients (ie, blood
pressure <130/80 mmHg) who have had an ischemic stroke or TIA due to a
cardioembolic phenomenon (eg, atrial fibrillation).
Antihypertensive therapy…cont’d

In patients with acute ischemic stroke (ie, the first hours


and days after onset), it is important not to lower the
blood pressure too quickly.
Lifestyle modifications that have been associated with
blood pressure reductions should be included as part of
the antihypertensive regimen.
weight loss,
salt restriction,
a diet rich in fruits, vegetables, and low-fat dairy products,
regular aerobic physical activity, and
limited alcohol consumption.
Antithrombotic therapy
For noncardioembolic ischemic stroke or TIA of
atherothrombotic, lacunar (small vessel occlusive), or
cryptogenic type should be treated with an antiplatelet
agent.
Aspirin (50 to 100 mg daily),
clopidogrel (75 mg daily), and
The combination of aspirin-extended-release dipyridamole (25
mg/200 mg twice a day).
Early, short-term dual antiplatelet therapy (DAPT),
typically with aspirin plus clopidogrel, is beneficial for
select patients with high-risk TIA or minor ischemic
stroke, and may be beneficial for patients with recently
symptomatic intracranial large artery atherosclerosis.
Anticoagulation Therapy
Long-term anticoagulation with warfarin or a direct oral
anticoagulant (DOAC; dabigatran, apixaban, rivaroxaban,
or edoxaban) is recommended as prevention for patients with
chronic nonvalvular atrial fibrillation who have had an ischemic
stroke or transient ischemic attack.
Other potential cardiac sources of embolism for which
anticoagulation therapy may be indicated for select patients
include the following:
Mechanical heart valves and a subpopulation of high-risk patients
with bioprosthetic valves
Left ventricular thrombus
Dilated cardiomyopathy
Rheumatic valve disease
Recent myocardial infarction in high-risk patients
LDL-Clowering therapy
In patients with hyperlipidemia, treatment with HMG-CoA
reductase inhibitors (statins) decreases the risk of stroke, while
lipid lowering by other means (eg, fibrates, resins, diet) has no
significant impact on stroke incidence.
The protective effects of statins are not mediated by
cholesterol lowering, but by anti-atherothrombotic properties.
In addition to their cholesterol lowering properties, statins also
have a role in:
plaque stabilization,
reducing inflammation,
slowing carotid arterial disease progression,
improving endothelial function, and
reducing embolic stroke by prevention of myocardial infarction and
left ventricular dysfunction.
LDL-Clowering therapy …cont’d
High-intensity statin therapy (atorvastatin 80 mg/day) is
recommended for patients with TIA or ischemic stroke of
atherosclerotic origin who are able to tolerate statins, independent of
the baseline low-density lipoprotein cholesterol (LDL-C), to reduce the
risk of stroke and cardiovascular events.
For patients who are intolerant of high-intensity statin therapy,
alternatives are:
moderate-intensity statin therapy (eg, atorvastatin 10 to 20 mg
daily, rosuvastatin 5 to 10 mg daily, simvastatin 20 to 40 mg
daily, pravastatin 40 to 80 mg daily, lovastatin 40 mg daily, or fluvastatin 40
mg daily in two divided doses) or
low-intensity statin therapy (eg, pravastatin 10 to 20 mg daily or lovastatin 20
mg daily) if tolerated.
For patients whose LDL-C level remains ≥70 mg/dL (≥1.8 mmol/L)
despite maximally tolerated statin therapy, adding ezetimibe or a
proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is
reasonable [87].
For patients who are unable to tolerate any statin regimen, we
suggest treatment with ezetimibe
Glycemic control
For patients with diabetes who have had an ischemic stroke or
TIA, we suggest glucose control to near normoglycemic levels.
Tight glucose control reduces microvascular complications.
Diet, exercise, oral hypoglycemic drugs, and insulin are proven
methods to achieve glycemic control.
A reasonable goal of therapy is an A1C value of ≤7 percent for
most patients.
However, the available evidence has not demonstrated a
consistent beneficial effect of intensive glucose-lowering
therapy or lifestyle modification for macrovascular outcomes
(eg, stroke and death) in patients with type 2 diabetes.
Treatment of insulin resistance
Disordered glucose metabolism appears to be common among
nondiabetic patients with ischemic stroke or TIA; one small
study found a prevalence of 50 percent on the basis of an
abnormal oral glucose tolerance test.
Pioglitazone treatment appears to reduce the risk of recurrent
stroke and myocardial infarction in nondiabetic patients who
have insulin resistance, though this benefit is partially offset by
an increased risk of adverse effects such as bone fracture.
The number needed to treat (NNT) with pioglitazone to prevent
one patient from developing stroke or myocardial infarction is
36, while the number needed to harm (NNH) to cause one
patient to develop bone fracture requiring hospitalization is 53.

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Lifestyle modification
A number of behavioral and lifestyle modifications may be
beneficial for reducing the risk of ischemic stroke and
cardiovascular disease.
These include:
smoking cessation,
limited alcohol consumption,
weight control,
regular aerobic physical activity,
moderate to vigorous intensity physical exercise most days of the week for
at least 40 minutes
moderate intensity exercise is defined as activity sufficient to break a sweat
or noticeably raise the heart rate
salt restriction, and
a Mediterranean diet
Diet
Patients with a history of stroke or TIA, are encouraged to
follow a Mediterranean-type diet that emphasizes the intake of
vegetables, fruits, whole grains, low-fat dairy products, poultry,
fish, legumes, nontropical vegetable oils, and nuts.
Limits the intake of sweets, sugar-sweetened beverages, and
red meats.
Calories from saturated fat should be limited to 5 to 6 percent
and calories from trans-fat should be reduced.
For patients who would benefit from blood pressure lowering,
a reduction in sodium (< 2400 mg per day) is also suggested.

The 2013 American Heart Association/American College of Cardiology (AHA/ACC) guideline on lifestyle management
to reduce cardiovascular risk;
The 2014 AHA/ASA guideline for stroke prevention in patients with stroke or TIA
Weight reduction
Weight reduction for obese patients is potentially
beneficial for improved control of other important
parameters, including blood pressure, blood glucose,
and serum lipid levels.
The 2014 AHA/ASA guidelines for stroke prevention
recommend screening all patients with stroke or TIA
for obesity with measurement of body mass index

40
Revascularization
Revascularization of the cervical
internal carotid artery with
endarterectomy or stenting is
beneficial for patients with recently
symptomatic ICA atherosclerotic
disease
There is no proven benefit of
revascularization for patients with
large vessel atherothrombotic
disease in anterior and posterior
cerebral circulation sites other than
the cervical internal carotid artery.
Polypills
Contain various combinations of statins, antihypertensive
medications, and aspirin.
Potential advantages include increased compliance and decreased
costs.
May be useful as a population-based strategy in resource limited
settings.
Potential disadvantages include increased adverse effects, individual
patient variability concerning the optimal combination of
medications, and difficulty in titration.
Contained hydrochlorothiazide 12.5 mg, aspirin 81
mg, atorvastatin 20 mg, and enalapril 5 mg; participants who
developed a cough were switched to a polypill
containing valsartan 40 mg instead of enalapril.
The polypill demonstrated efficacy in both primary and secondary
prevention.
INTRODUCTION
RISK FACTORS AND MECHANISMS
INTERVENTIONS
SUMMARY AND RECOMMENDATIONS
SUMMARY AND RECOMMENDATIONS
1. The major treatable atherosclerotic stroke risk factors are hypertension, diabetes,
smoking, and dyslipidemia. Common causes of ischemic stroke amenable to treatment
include atrial fibrillation and carotid artery stenosis.
2. Most patients with an ischemic stroke or transient ischemic attack (TIA) should be
treated with all available risk reduction strategies.
3. Resumption of antihypertensive therapy is recommended for:
Previously treated patients with known hypertension who are beyond the first few days
after stroke onset.
Patients previously untreated with antihypertensive therapy who are beyond the first
few days after stroke onset, we make the following recommendations:
Patients with ischemic stroke or TIA of any type who have an established blood
pressure ≥140 mmHg systolic or ≥90 mmHg diastolic.
Patients with ischemic stroke or TIA of atherothrombotic, lacunar (small vessel
occlusive), or cryptogenic type, and an established blood pressure >120 mmHg
systolic or >70 mmHg diastolic.

Antihypertensive therapy should not be recommended for nonhypertensive patients (ie,


blood pressure <130/80 mmHg) who have had a stroke or TIA due to a cardioembolic
phenomenon (eg, atrial fibrillation).
SUMMARY....cont’d
4. Nearly all patients with TIA or ischemic stroke of atherosclerotic
origin should be treated with an antiplatelet agent. Long-term
anticoagulation should be used as prevention for patients with
chronic nonvalvular atrial fibrillation who have had an ischemic
stroke or transient ischemic attack.
5. For patients with TIA or ischemic stroke of atherosclerotic origin
who are able to tolerate statins, we suggest high-intensity statin
therapy, independent of the baseline low-density lipoprotein
cholesterol (LDL-C), to reduce the risk of stroke and cardiovascular
events. For patients whose LDL-C level remains ≥70 mg/dL (≥1.8
mmol/L) despite maximally tolerated statin therapy,
adding ezetimibe or a proprotein convertase subtilisin/kexin type 9
(PCSK9) inhibitor is reasonable. For patients who are unable to
tolerate any statin regimen, we suggest treatment with ezetimibe.
SUMMARY....cont’d
6. For patients with diabetes who have had an ischemic stroke or TIA, we
suggest glucose control to near normoglycemic levels.
7. A number of behavioral and lifestyle modifications may be beneficial for
reducing the risk of ischemic stroke and cardiovascular disease:
All patients who are recent or current tobacco smokers should be counseled routinely
to quit smoking.
Patients who are heavy drinkers should eliminate or reduce alcohol consumption.
For patients with ischemic stroke or TIA who are capable of regular exercise, we
suggest moderate to vigorous intensity physical exercise for at least 40 minutes most
days of the week.
For patients with ischemic stroke or TIA, we suggest a Mediterranean diet that
emphasizes intake of vegetables, fruits, and whole grains. In addition, for patients
who would benefit from blood pressure lowering, we suggest restricting sodium
intake to no more than 2400 mg per day.
Weight reduction for obese patients is potentially beneficial for improved control of
blood pressure, blood glucose, and serum lipid levels.

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