Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

atherosclerotic ischemic disease

1st line – antiplatelet therapy

Back
ONGOING
|
atherosclerotic ischemic disease
1st line – 

antiplatelet therapy

Evidence supports the use of aspirin monotherapy, or combination treatment with aspirin plus clopidogrel or aspirin plus ticagrelor, for preventing further infarction in patients with stroke or transient ischemic attack (TIA) relating to large artery atherosclerotic disease.​[72]​​​​

The selection of antiplatelet agent should be individualized on the basis of patient risk factor profiles, tolerance, relative known efficacy of the agents, and other clinical characteristics.

There is no good evidence that aspirin is effective in treating cognitive symptoms in patients with vascular dementia.[73]

Primary options

aspirin: 81-325 mg orally once daily

OR

aspirin: 81-325 mg orally once daily

and

clopidogrel: 75 mg orally once daily

Secondary options

aspirin: 81-325 mg orally once daily

and

ticagrelor: 90 mg orally twice daily

Plus – lifestyle modification

Back
ONGOING
|
atherosclerotic ischemic disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Physical activity and dietary modification can assist in reducing blood pressure and controlling glucose, thereby reducing stroke risk. Patients who are able to exercise should undertake 40 minutes of moderate- to vigorous-intensity exercise 3 to 4 times per week. Smokers should be advised to stop smoking. Patients with a high alcohol intake should be advised to reduce their intake or stop drinking altogether.​[72]

Plus – supportive care

Back
ONGOING
|
atherosclerotic ischemic disease
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Provide education, support, and resources to the patient and their families and caregivers. Information should cover topics such as how symptoms are likely to progress, future care needs (including early care planning), and advance directives or power of attorney for health care. Discuss the benefits and risks of nonpharmacologic and pharmacologic treatments with the patient and family, so that informed decisions can be made. A social worker, psychologist, or other mental health professional should be made available to provide emotional support and psychosocial input. Advise families and caregivers about further sources of information and caregiver support groups.[118]

A home safety evaluation should be undertaken, as well as an assessment of transport, driving, and self-care needs by an occupational therapist.[119] Impaired gait and balance are typical of vascular dementia, so it is important that falls risk is assessed, and interventions to mitigate this risk put in place.

Late-/end-stage care includes palliative measures, end-of-life choices, and discussing goals of care with the family.[120][121] It is important to review these issues in late-stage dementia, as overly aggressive care such as percutaneous endoscopic gastrostomy feeding tubes can worsen morbidity and not improve quality of life or longevity.[122] Many patients and families do not want extreme measures if there is no possibility of independent function. Exploring family and patient preferences in the context of medical literature and information is very helpful.

Plus – carotid endarterectomy or carotid angioplasty and stenting

Back
ONGOING
|
atherosclerotic ischemic disease
|
with carotid stenosis ≥70%
Plus – 

carotid endarterectomy or carotid angioplasty and stenting

Treatment recommended for ALL patients in selected patient group

Carotid endarterectomy is the preferred treatment for unilateral symptomatic carotid stenosis (grade >70%) in patients who have had a nondisabling stroke or TIA within the last 6 months.​​​[72]

Carotid angioplasty and stenting is indicated as an alternative to carotid endarterectomy for symptomatic patients at average or low risk of complications associated with endovascular intervention when the diameter of the internal carotid artery lumen is reduced by >70% by noninvasive imaging or >50% by catheter-based imaging or noninvasive imaging with corroboration, and the anticipated rate of periprocedural stroke or death is <6%.​[72]

It is reasonable to consider patient age in choosing between carotid angioplasty and stenting and carotid endarterectomy. For patients older than 70 years, carotid endarterectomy may be associated with improved outcome compared with carotid angioplasty and stenting, particularly when arterial anatomy is unfavorable for endovascular intervention.​[72]​ 

See Carotid artery stenosis (Management).

Plus – cholinesterase inhibitor and/or memantine

Back
ONGOING
|
atherosclerotic ischemic disease
|
concomitant Alzheimer disease (AD)
Plus – 

cholinesterase inhibitor and/or memantine

Treatment recommended for ALL patients in selected patient group

These may help delay cognitive decline in people with concomitant AD.[82]

Cholinesterase inhibitors are indicated for mild to severe AD. Clinical benefits are modest, but have been reported to continue beyond 1 year with ongoing treatment.[82][84]

Memantine is indicated for moderate to severe AD.[80]

Co-administration of memantine with a cholinesterase inhibitor may be considered as the severity of AD worsens. Memantine can be given as sole treatment if cholinesterase inhibitors are contraindicated, are not tolerated, and/or have been shown to be ineffective. Medication should be started at the lowest possible dose and titrated gradually.

Donepezil and galantamine appear to have the greatest effect on cognition for patients with vascular cognitive impairment.[81]

Cholinesterase inhibitors are known to have cardiovascular effects, as well as neurologic, and with long-term treatment, there is good evidence to confirm that they reduce all-cause mortality in dementia patients.[85]

Primary options

donepezil: 5 mg orally once daily initially, increase to 10 mg once daily after 4-6 weeks according to response, maximum 10 mg/day

or

galantamine: 4 mg orally (immediate-release) twice daily initially, increase by 8 mg/day increments every 4 weeks according to response, maximum 24 mg/day; 8 mg orally (extended-release) once daily initially, increase by 8 mg/day increments every 4 weeks according to response, maximum 24 mg/day

or

rivastigmine: 1.5 mg orally twice daily initially, increase by 3 mg/day increments every 4 weeks, maximum 12 mg/day

or

rivastigmine transdermal: 4.6 mg/24 hour patch once daily, may increase to 9.5 mg/24 hour patch once daily after 4 weeks according to response

-- AND / OR --

memantine: 7 mg orally (extended-release) once daily initially, increase by 7 mg/day increments every 7 days according to response, maximum 28 mg/day

Plus – blood pressure (BP) control

Back
ONGOING
|
atherosclerotic ischemic disease
|
with hypertension
Plus – 

blood pressure (BP) control

Treatment recommended for ALL patients in selected patient group

Initiation of BP-lowering therapy is indicated for previously untreated patients with ischemic stroke or transient ischemic attack (TIA) who, after the first few days, have an established BP ≥140 mmHg systolic or ≥90 mmHg diastolic. Initiation of therapy for patients with BP <140 mmHg systolic and <90 mmHg diastolic is of uncertain benefit.​[72]

Resumption of BP-lowering therapy is indicated after the first few days for patients who have had an ischemic stroke or TIA and were treated previously for known hypertension.​[72]​ Goals for target BP level or reduction from pretreatment baseline are uncertain and should be individualized, but it is reasonable to achieve a systolic pressure <140 mmHg and a diastolic pressure <90 mmHg. For patients with a recent lacunar stroke, it might be reasonable to target a systolic BP of <130 mmHg.​[72]

Plus – statin therapy

Back
ONGOING
|
atherosclerotic ischemic disease
|
with elevated low-density lipoprotein (LDL) cholesterol
Plus – 

statin therapy

Treatment recommended for ALL patients in selected patient group

There is good evidence to support the use of statins in secondary stroke prevention.[95][96][97]​​

Atorvastatin is the only statin that has been directly tested for secondary stroke prevention, although others have been shown to be effective in lowering cardiovascular disease risk.[123]

High-intensity statin treatment is recommended for patients ages ≤75 years with clinical atherosclerotic cardiovascular disease (ASCVD) events, unless contraindicated or associated with significant adverse effects (in which case maximally tolerated statin therapy should be used). For patients ages >75 years with clinical ASCVD, high- or moderate-intensity statin therapy may be used following an evaluation of the potential benefits and harms and the patient’s preferences.[97]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

Secondary options

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

Plus – optimization of glycemic control

Back
ONGOING
|
atherosclerotic ischemic disease
|
with diabetes mellitus
Plus – 

optimization of glycemic control

Treatment recommended for ALL patients in selected patient group

Optimizing glucose control can affect macrovascular and microvascular disease risk.[98] The goal for hemoglobin A1c (HbA1c) should be ≤7%.​[72]

After a transient ischemic attack or ischemic stroke, all patients should be screened for diabetes with testing of fasting plasma glucose, HbA1c, or an oral glucose tolerance test. Choice of test and timing should be guided by clinical judgment and recognition that acute illness may temporarily perturb measures of plasma glucose. HbA1c may be more accurate than other screening tests in the immediate postevent period.​[72]

Plus – antidepressant plus nonpharmacologic strategies

Back
ONGOING
|
atherosclerotic ischemic disease
|
with depression
Plus – 

antidepressant plus nonpharmacologic strategies

Treatment recommended for ALL patients in selected patient group

Depression is common in patients with vascular dementia.[110] The available evidence does not provide strong support for the efficacy of antidepressants for treating depression in dementia.[111] However, clinical consensus supports undertaking a trial of an antidepressant to treat clinically significant depression in people with dementia.[112]

Selective serotonin-reuptake inhibitors (SSRIs) such as sertraline, citalopram, and escitalopram are preferred. SSRIs with a longer half-life (i.e., fluoxetine), those with increased potential for drug-drug interactions mediated by cytochrome P450 (fluoxetine, paroxetine, fluvoxamine), and those known to be more activating (e.g., paroxetine) should be used with caution. Mirtazapine, an atypical antidepressant, is appropriate when poor appetite and insomnia are present.

SSRIs and mirtazapine increase risk of QT prolongation and should be used with caution in patients with conditions that also increase the risk of QT prolongation (e.g., bradycardia, heart failure, cardiomyopathy, stroke, myocardial infarction); regular ECG monitoring is needed. There is an increased risk of bleeding with SSRIs, so caution and monitoring are needed if the patient is taking an anticoagulant or antiplatelet agent. Mirtazapine can cause orthostatic hypotension and so should be used with caution in patients with cerebrovascular disease that can be exacerbated by hypotension.

Symptoms of depression may be improved by encouraging social gatherings and activities (such as gardening, cleaning, and setting the table) to provide the person with routine and foster a sense of utility. Psychological interventions (e.g., cognitive behavioral therapy, interpersonal therapies) may reduce depression and anxiety in people with dementia.[105]

Primary options

sertraline: 50-200 mg orally once daily

OR

citalopram: <60 years of age: 20-40 mg orally once daily; ≥60 years of age: 10-20mg orally once daily

OR

escitalopram: 10-20 mg orally once daily

Secondary options

mirtazapine: 15-45 mg orally once daily

Plus – selective serotonin-reuptake inhibitor (SSRI) plus nonpharmacologic strategies

Back
ONGOING
|
atherosclerotic ischemic disease
|
with agitation or aggression
Plus – 

selective serotonin-reuptake inhibitor (SSRI) plus nonpharmacologic strategies

Treatment recommended for ALL patients in selected patient group

The SSRIs citalopram and sertraline reduce symptoms of agitation compared with placebo in people with dementia, although there was no specific evidence for people with vascular dementia.[113]

SSRIs increase risk of QT prolongation and should be used with caution in patients with conditions that also increase the risk of QT prolongation (e.g., bradycardia, heart failure, cardiomyopathy, stroke, myocardial infarction); regular ECG monitoring is needed. There is an increased risk of bleeding with SSRIs, so caution and monitoring are needed if the patient is taking an anticoagulant or antiplatelet agent.

Antipsychotics should be avoided in people with vascular dementia because of the reported increased incidence of stroke and myocardial infarction in people taking these drugs, in addition to evidence of increased mortality with both typical and atypical antipsychotic use in patients with dementia.[114][115][116][117]

Nonpharmacologic strategies may help to lessen agitation. Actions include explaining caregiver actions in advance, giving written instructions, and using calendars, clocks, and charts to help patients stay oriented to the time and place. There is some evidence that personally tailored activities can reduce challenging behavior in people with dementia living in the community.[104]

Primary options

sertraline: 50-200 mg orally once daily

OR

citalopram: <60 years of age: 20-40 mg orally once daily; ≥60 years of age: 10-20mg orally once daily

cardioembolic disease

1st line – anticoagulation

Back
ONGOING
|
cardioembolic disease
1st line – 

anticoagulation

Warfarin is highly effective in reducing the risk of cardioembolic stroke in patients with atrial fibrillation.[72]​ The direct-acting oral anticoagulants dabigatran, apixaban, rivaroxaban, and edoxaban are also highly effective in reducing the risk of cardioembolic stroke in nonvalvular atrial fibrillation.[72]

See Established atrial fibrillation (Management).​

Primary options

warfarin: 5 mg orally once daily initially, adjust dose according to INR (target 2-3)

OR

rivaroxaban: 20 mg orally once daily

OR

apixaban: 2.5 to 5 mg orally twice daily

OR

dabigatran etexilate: 150 mg orally twice daily

OR

edoxaban: 60 mg orally once daily

Plus – lifestyle modification

Back
ONGOING
|
cardioembolic disease
Plus – 

lifestyle modification

Treatment recommended for ALL patients in selected patient group

Physical activity and dietary modifications can assist in reducing blood pressure and controlling glucose, thereby reducing stroke risk. Patients who are able to exercise should undertake 40 minutes of moderate- to vigorous-intensity exercise 3 to 4 times per week. Smokers should be advised to stop smoking. Patients with a high alcohol intake should be advised to reduce their intake or stop drinking altogether.​[72]

Plus – supportive care

Back
ONGOING
|
cardioembolic disease
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Provide education, support, and resources to the patient and their families and caregivers. Information should cover topics such as how symptoms are likely to progress, future care needs (including early care planning), and advance directives or power of attorney for health care. Discuss the benefits and risks of nonpharmacologic and pharmacologic treatments with the patient and family, so that informed decisions can be made. A social worker, psychologist, or other mental health professional should be made available to provide emotional support and psychosocial input. Advise families and caregivers about further sources of information and caregiver support groups.[118]

A home safety evaluation should be undertaken, as well as an assessment of transport, driving, and self-care needs by an occupational therapist.[119] Impaired gait and balance are typical of vascular dementia, so it is important that fall risk is assessed, and interventions to mitigate this risk put into place.

Late-/end-stage care includes palliative measures, end-of-life choices, and discussing goals of care with the family.[120][121] It is important to review these issues in late-stage dementia, as overly aggressive care such as percutaneous endoscopic gastrostomy feeding tubes can worsen morbidity and not improve quality of life or longevity.[122] Many patients and families do not want extreme measures if there is no possibility of independent function. Exploring family and patient preferences in the context of medical literature and information is very helpful.

Plus – cholinesterase inhibitor and/or memantine

Back
ONGOING
|
cardioembolic disease
|
concomitant Alzheimer disease (AD)
Plus – 

cholinesterase inhibitor and/or memantine

Treatment recommended for ALL patients in selected patient group

These may help to delay cognitive decline in people with concomitant AD.[82]

Cholinesterase inhibitors are indicated for mild to severe AD. Clinical benefits are modest, but have been reported to continue beyond 1 year with ongoing treatment.[82][84]

Memantine is indicated for moderate to severe AD.[80]

Co-administration of memantine with a cholinesterase inhibitor may be considered as the severity of AD worsens. Memantine can be given as sole treatment if cholinesterase inhibitors are contraindicated, are not tolerated, and/or have been shown to be ineffective. Medication should be started at the lowest possible dose and titrated gradually.

Donepezil and galantamine appear to have the greatest effect on cognition for patients with vascular cognitive impairment.[81]

Cholinesterase inhibitors are known to have cardiovascular effects, as well as neurologic, and with long-term treatment, there is good evidence to confirm that they reduce all-cause mortality in dementia patients.[85]

Primary options

donepezil: 5 mg orally once daily initially, increase to 10 mg once daily after 4-6 weeks according to response, maximum 10 mg/day

or

galantamine: 4 mg orally (immediate-release) twice daily initially, increase by 8 mg/day increments every 4 weeks according to response, maximum 24 mg/day; 8 mg orally (extended-release) once daily initially, increase by 8 mg/day increments every 4 weeks according to response, maximum 24 mg/day

or

rivastigmine: 1.5 mg orally twice daily initially, increase by 3 mg/day increments every 4 weeks, maximum 12 mg/day

or

rivastigmine transdermal: 4.6 mg/24 hour patch once daily, may increase to 9.5 mg/24 hour patch once daily after 4 weeks according to response

-- AND / OR --

memantine: 7 mg orally (extended-release) once daily initially, increase by 7 mg/day increments every 7 days according to response, maximum 28 mg/day

Plus – blood pressure (BP) control

Back
ONGOING
|
cardioembolic disease
|
with hypertension
Plus – 

blood pressure (BP) control

Treatment recommended for ALL patients in selected patient group

Initiation of BP-lowering therapy is indicated for previously untreated patients with ischemic stroke or transient ischemic attack (TIA) who, after the first few days, have an established BP ≥140 mmHg systolic or ≥90 mmHg diastolic. Initiation of therapy for patients with BP <140 mmHg systolic and <90 mmHg diastolic is of uncertain benefit.​[72]

Resumption of BP-lowering therapy is indicated after the first few days for patients who have had an ischemic stroke or TIA and were treated previously for known hypertension.​[72]

Goals for target BP level or reduction from pretreatment baseline are uncertain and should be individualized, but it is reasonable to achieve a systolic pressure <140 mmHg and a diastolic pressure <90 mmHg. For patients with a recent lacunar stroke, it might be reasonable to target a systolic BP of <130 mmHg.​[72]

Plus – statin therapy

Back
ONGOING
|
cardioembolic disease
|
with elevated low-density lipoprotein (LDL) cholesterol
Plus – 

statin therapy

Treatment recommended for ALL patients in selected patient group

There is good evidence to support the use of statins in secondary stroke prevention.[95][96][97]​​​​

Atorvastatin is the only statin that has been directly tested for secondary stroke prevention, although others have been shown to be effective in lowering cardiovascular disease risk.[123]

High-intensity statin treatment is recommended for patients ages ≤75 years with clinical atherosclerotic cardiovascular disease (ASCVD) events, unless contraindicated or associated with significant adverse effects (in which case maximally tolerated statin therapy should be used). For patients ages >75 years with clinical ASCVD, high- or moderate-intensity statin therapy may be used following an evaluation of the potential benefits and harms and the patient’s preferences.[97]

Primary preventative treatment with maximally tolerated statin therapy is recommended for patients ages 20 to 75 years with severe hypercholesterolemia (LDL-cholesterol level ≥4.9 mmol/L). Primary preventative treatment with a moderate-intensity statin is recommended for patients ages 40 to 75 years with diabetes. Primary preventative therapy may also be initiated following a risk discussion between the clinician and the patient.[97]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

Secondary options

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

Plus – optimization of glycemic control

Back
ONGOING
|
cardioembolic disease
|
with diabetes mellitus
Plus – 

optimization of glycemic control

Treatment recommended for ALL patients in selected patient group

Optimizing glucose control can affect macrovascular and microvascular disease risk.[98] The goal for hemoglobin A1c (HbA1c) should be ≤7%.​[72]

After a transient ischemic attack or ischemic stroke, all patients should be screened for diabetes with testing of fasting plasma glucose, HbA1c, or an oral glucose tolerance test. Choice of test and timing should be guided by clinical judgment and recognition that acute illness may temporarily perturb measures of plasma glucose. HbA1c may be more accurate than other screening tests in the immediate postevent period.​[72]

Plus – antidepressant plus nonpharmacologic strategies

Back
ONGOING
|
cardioembolic disease
|
with depression
Plus – 

antidepressant plus nonpharmacologic strategies

Treatment recommended for ALL patients in selected patient group

Depression is common in patients with vascular dementia.[110] The available evidence does not provide strong support for the efficacy of antidepressants for treating depression in dementia.[111] However, clinical consensus supports undertaking a trial of an antidepressant to treat clinically significant depression in people with dementia.[112]

Selective serotonin-reuptake inhibitors (SSRIs) such as sertraline, citalopram, and escitalopram are preferred. SSRIs with a longer half-life (i.e., fluoxetine), those with increased potential for drug-drug interactions mediated by cytochrome P450 (fluoxetine, paroxetine, fluvoxamine), and those known to be more activating (e.g., paroxetine) should be used with caution. Mirtazapine, an atypical antidepressant, is appropriate when poor appetite and insomnia are present.

SSRIs and mirtazapine increase risk of QT prolongation and should be used with caution in patients with conditions that also increase the risk of QT prolongation (e.g., bradycardia, heart failure, cardiomyopathy, stroke, myocardial infarction); regular ECG monitoring is needed. There is an increased risk of bleeding with SSRIs, so caution and monitoring are needed if the patient is taking an anticoagulant or antiplatelet agent. Mirtazapine can cause orthostatic hypotension and so should be used with caution in patients with cerebrovascular disease that can be exacerbated by hypotension.

Symptoms of depression may be improved by encouraging social gatherings and activities (such as gardening, cleaning, and setting the table) to provide the person with routine and foster a sense of utility. Psychological interventions (e.g., cognitive behavioral therapy, interpersonal therapies) may reduce depression and anxiety in people with dementia.[105]

Primary options

sertraline: 50-200 mg orally once daily

OR

citalopram: <60 years of age: 20-40 mg orally once daily; ≥60 years of age: 10-20mg orally once daily

OR

escitalopram: 10-20 mg orally once daily

Secondary options

mirtazapine: 15-45 mg orally once daily

Plus – selective serotonin-reuptake inhibitor (SSRI) plus nonpharmacologic strategies

Back
ONGOING
|
cardioembolic disease
|
with agitation or aggression
Plus – 

selective serotonin-reuptake inhibitor (SSRI) plus nonpharmacologic strategies

Treatment recommended for ALL patients in selected patient group

The SSRIs citalopram and sertraline reduce symptoms of agitation compared with placebo in people with dementia, although there was no separate evidence for people with vascular dementia.[113]

SSRIs increase risk of QT prolongation and should be used with caution in patients with conditions that also increase the risk of QT prolongation (e.g., bradycardia, heart failure, cardiomyopathy, stroke, myocardial infarction); regular ECG monitoring is needed. There is an increased risk of bleeding with SSRIs, so caution and monitoring are needed if the patient is taking an anticoagulant or antiplatelet agent.

Antipsychotics should be avoided in people with vascular dementia because of the reported increased incidence of stroke and myocardial infarction in people taking these drugs, in addition to evidence of increased mortality with both typical and atypical antipsychotic use in patients with dementia.[114][115][116][117]

Nonpharmacologic strategies may help to lessen agitation. Actions include explaining caregiver actions in advance, giving written instructions, and using calendars, clocks, and charts to help patients stay oriented to the time and place. There is some evidence that personally tailored activities can reduce challenging behavior in people with dementia living in the community.[104]

Primary options

sertraline: 50-200 mg orally once daily

OR

citalopram: <60 years of age: 20-40 mg orally once daily; ≥60 years of age: 10-20mg orally once daily

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer