Transcript Secondary Stroke Prevention

Secondary stroke prevention
Clin/A/Prof Darshan Ghia
MBBS(Hons) MD DNB FRACP
Clinical Senior lecturer, School of Medicine and Pharmacology, UWA
Consultant Neurologist and Head of stoke unit, Fiona Stanley hospital
[email protected]
Introduction
 The world is facing a stroke epidemic:
 between 1990 and 2010, the number of stroke-related deaths
increased by 26%
 disability-adjusted life-years by 19%
 stroke the second leading cause of death
 third leading contributor to disability-adjusted life-years in the
world.
Importance of secondary stroke prevention
 Survivors of stroke and transient ischaemic attacks are at risk of a
recurrent stroke, which is often more severe, disabling even fatal
and costlier than the index event.
 Recurrent strokes continue to account for 25–30% of all strokes and
represent unsuccessful secondary prevention
 Immediate and sustained implementation of effective and
appropriate secondary prevention strategies in patients with firstever stroke or transient ischaemic attack has the potential to reduce
the burden of stroke by up to a quarter
Early recurrent stroke
Prognosis
 The risk of a recurrent stroke after an ischaemic stroke or TIA
 1% at 6 h
 2% at 12 h
 3% at 2 days
 5% at 7 days
 10% at 14 days
 Therefore, ischaemic stroke or TIA is a medical emergency that
demands immediate diagnosis and treatment.
Early recurrent stroke
Acute specialty units
 Patients with suspected TIA should be assessed and managed
urgently in an acute specialty unit, such as a dedicated TIA clinic
 Patients with acute stroke should be ideally managed in a stroke
unit environment
 Investigations usually comprise
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immediate imaging of the brain, arteries to the brain, and heart;
electrocardiograph;
measurement of fasting blood glucose and lipids
Holter and echocardiogram
Early recurrent stroke
Antiplatelet therapy
 All patients with acute TIA and ischaemic stroke should be given at
least 160 mg of aspirin or acetylsalicylic acid immediately as a
single loading dose
 In dysphagic patients, aspirin can be given by enteral tube or by
rectal suppository
 In patients given recombinant tissue plasminogen activator,aspirin
should be delayed until after the 24 h post-thrombolysis scan has
excluded intracranial haemorrhage
 Aspirin (50–150 mg daily) should then be continued indefinitely or
until an alternative antithrombotic regimen is started
Early recurrent stroke
Antiplatelet therapy
 For patients taking aspirin before ischaemic stroke or TIA,
clopidogrel can be considered as an alternative
 If rapid action is required, use a loading dose of 300 mg or 600 mg
of clopidogrel, followed by a maintenance dose of 75 mg once daily
 Chinese patients with acute (<24 h) TIA or minor ischaemic stroke
should be given a bolus loading dose of at least 160 mg of aspirin
and 300 mg of clopidogrel immediately, followed by clopidogrel 75
mg plus aspirin 75 mg for 21 days, and single antiplatelet agent long
term.
Early recurrent stroke
Anticoagulation therapy
 Existing evidence does not support the routine or selective
immediate use of any anticoagulants in acute ischaemic stroke of
presumed arterial or cardiac origin
 The optimum timing of oral anticoagulation after acute cardioembolic
ischaemic stroke is unclear; it is common practice to wait 2–14 days
and repeat brain imaging (CT or MRI) to rule out asymptomatic
intracranial haemorrhage before starting oral anticoagulation
 Patients with atrial fibrillation and acute transient ischaemic attack
can begin oral anticoagulation (warfarin, dabigatran, rivaroxaban, or
apixaban) immediately because the risk of intracranial haemorrhage
is probably low (ie, there is no fresh brain infarction to become
haemorrhagic).
Early recurrent stroke
Statins
 Observational studies suggest that statin treatment at the onset of
TIA in patients with symptomatic carotid stenosis is associated with
reduced risk of early recurrent stroke.
Merwick A, Albers GW, Arsava EM, et al. Reduction in early stroke risk in carotid stenosis with transient
ischemic attack associated with statin treatment. Stroke 2013; 44: 2814–20.
 However, the few small randomised controlled trials of statins in
acute TIA and ischaemic stroke have not shown, nor had the
statistical power to show, that early initiation of high-dose statins
safely and effectively reduces the risk of early recurrent stroke
Beer C, Blacker D, Bynevelt M, Hankey GJ, Puddey IB. A randomized placebo controlled trial of early
treatment of acute ischemic stroke with atorvastatin and irbesartan. Int J Stroke 2012;7: 104–11.
Early recurrent stroke
Carotid revascularisation
 Patients with TIA or non-disabling ischaemic stroke and ipsilateral
50–99% internal carotid artery stenosis should be offered carotid
endarterectomy :
 measured by two concordant non-invasive imaging modalities
 as soon as possible, ideally within the first few days and up to 1 week
after the ischaemic event
 patients are fit and willing for surgery
 done by a surgeon with an audited perioperative morbidity and mortality
of less than 5%
 Carotid stenting might be as safe as endarterectomy in patients less
than 70 years of age and for patients who are not candidates for
carotid endarterectomy because of technical, anatomical, or medical
reasons
Long-term recurrent stroke
Prognosis
 The risk of recurrent stroke in survivors of acute stroke is about
 11·1% at 1 year
 26·4% at 5 years
 39·2% at 10 years
 Predictors of a raised risk of recurrent stroke in the long term include
 prevalent vascular risk factors (older age, hypertension, diabetes, or smoking)
 Previous symptomatic vascular disease (stroke, myocardial infarction, or
peripheral arterial disease)
 Unstable vascular disease (several recurrent recent ischaemic events of the
brain, including the capsular warning syndrome)
 embolic sources and causes (atrial fibrillation or ischaemic stroke caused by
embolism from the heart or large arteries)
 and possibly cerebral microbleeds
Long-term recurrent stroke
Antiplatelet therapy
 Aspirin 50–325 mg daily, clopidogrel 75 mg daily, or the combination
of aspirin (25 mg) and extended-release dipyridamole (200 mg)
twice daily, are all appropriate options
 Long-term use (for >3 months) of aspirin and clopidogrel combined
is not recommended because of the cumulative risks of bleeding
Long-term recurrent stroke
Anticoagulation
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Patients with AF should be treated with anticoagulation, not antiplatelet
therapy
For some patients, the individual’s preferences, level of disability, prognosis,
and overall clinical status might preclude oral anticoagulation
Warfarin, dabigatran, apixaban and rivaroxaban are all indicated in nonvalvular atrial fibrillation.
The selection of an anticoagulant agent should be individualised on the
basis of renal and hepatic function, potential for drug interactions, patient
preference, tolerability, and other clinical characteristics, including time in
international normalised ratio therapeutic range if the patient has been
taking warfarin
Long-term recurrent stroke
Anticoagulation
 Apixaban 2.5 mg twice daily should be considered as an alternative
to aspirin in stroke patients with non-valvular atrial fibrillation who
are judged unsuitable for vitamin K antagonist therapy if their
creatinine clearance is >25 mL per min
 For patients with atrial fibrillation who have had a stroke but in whom
oral anticoagulation is contra indicated, the left atrial appendage can
be occluded by the WATCHMAN device (a self-expanding cage
placed in the left atrial appendage via a transeptal approach with
femoral access)
Long-term recurrent stroke
Blood pressure
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Gradual, sustained lowering of blood pressure is recommended in all stroke
patients, but care is needed, particularly in patients with carotid or
vertebrobasilar occlusive disease
The ideal time to start lowering of blood pressure after stroke is uncertain,
but it should be started before discharge from hospital
The optimum blood pressure-lowering drugs depend on patient
comorbidities
The target systolic blood pressure is lower than 130 mm Hg in patients with
lacunar stroke
Sustained lowering of blood pressure by 5·1 mm Hg systolic and 2·5 mm
Hg diastolic reduces recurrent stroke by about a fifth
Larger reductions in blood pressure—by 10 mm Hg systolic and 5 mm Hg
diastolic—are associated with larger reductions in recurrent stroke of about
a third
Long-term recurrent stroke
Statins
 LDL cholesterol concentration should be reduced by atherosclerosis
by means of diet and lifestyle modification and statin therapy
 The target LDL concentration is lower than 2 mmol/L, TG less than
1.8, total cholesterol less than 4 mmol/L and HDL more than 1
mmol/L.
 For patients with stroke who do not achieve a low enough LDL
cholesterol concentration, the addition of ezetimibe 10 mg, a
cholesterol absorption inhibitor, to statin therapy could produce
greater reductions in LDL
 Lowering of low-density lipoprotein (LDL) cholesterol concentration
by about 1 mmol/L with statins reduces the risk of recurrent stroke
by about 12%
Long-term recurrent stroke
Lifestyle behaviours
 Smoking
 Patients should stop smoking
 A combination of pharmacological (nicotine replacement therapy,
bupropion, cytisine, or varenicline) and behavioural therapy should be
considered
 Alcohol consumption
 Alcohol consumption should be limited to less than two standard drinks
per day;
 less than 14 drinks per week for men
 less than nine drinks per week for women
Long-term recurrent stroke
Lifestyle behaviours
 Physical activity
 Routine activities of daily living should be supplemented by
moderate physical exercise—walking (ideally briskly), jogging,
cycling, swimming, or other dynamic exercise
 For 30–60 min on 4–7 days per week
 High-risk patients (eg, those with cardiac disease) should
participate in medically supervised exercise programmes
 Bodyweight
 The BMI should be maintained at 18.5–24.9 kg/m2
 waist circumference less than 80 cm for women and
 less than 94 cm for men
Long-term recurrent stroke
Lifestyle behaviours
 Sodium
 The recommended adequate daily sodium intake for people
aged 9–50 years is 1500 mg, decreasing to 1300 mg for
individuals 50–70 years of age and to 1200 mg for those older
than 70 years.
 A daily upper consumption limit of 2300 mg should not be
exceeded by any age group
 Healthy balanced diet
 Eat a diet low in saturated fat, cholesterol, and sodium; and high
in fresh fruits, vegetables, low-fat dairy products, dietary and
soluble fibre, whole grains, and protein from plant sources
Long-term recurrent stroke
Ischaemic stroke from paradoxical embolism
 Patients with cryptogenic ischaemic stroke or TIA and a patent
foramen ovale have a similar rate of recurrent ischaemic stroke
(1·6% per year) as patients without a patent foramen ovale (1.1%)
 However, an additional atrial septal aneurysm increases the risk of
recurrent stroke (Hazard ratio 4.2)
 Possible strategies to reduce recurrent stroke from paradoxical
embolism include antiplatelet drugs, anticoagulation, and
percutaneous closure of the patent foramen ovale with a device.
Conclusions
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The combination of five of these strategies—aspirin, an antihypertensive
drug, a statin, exercise, and dietary modification—could reduce recurrent
stroke by 80%
We should initiate and document appropriate secondary prevention
medications according to guidelines while patients are still in hospital
Complementary multifaceted strategies involving the patient, caregiver,
doctors and pharmacists in the hospital and primary care setting are needed
We should address reasons for non-compliance, which include inadequate
clinican–patient interaction, inadequate instructions about correct intake,
complex drug regimes, adverse effects, and patient medication-taking
behaviour (not filling the prescription, and not taking the medication as
prescribed);
It is important to raise awareness in patients and their doctors of the need
for lifelong preventive treatment
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