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

ACUTE

small-vessel TIA

1st line – antiplatelet therapy

Back
ACUTE
|
small-vessel TIA
1st line – 

antiplatelet therapy

Preferred treatment is antiplatelet therapy.[94] It should be started in the first 24 hours, after intracranial hemorrhage is ruled out. Guidelines from the American Heart Association/American Stroke Association (AHA/ASA) recommend aspirin, clopidogrel, or aspirin/dipyridamole for secondary prevention of ischemic stroke.[21] In patients with high-risk TIA (ABCD2 score ≥4), guidelines from the AHA/ASA recommend that dual antiplatelet therapy should be initiated early (ideally within 12-24 hours of symptom onset and at least within 7 days of onset) and continued for 21 to 90 days, followed by single antiplatelet therapy, to reduce the risk of recurrent ischemic stroke.​[21][44]​​ Loading doses are recommended for dual antiplatelet therapy but not monotherapy.​​​[82]​​[83]​​[84]​​​

One meta-analysis found that dual antiplatelet therapy with clopidogrel plus aspirin (within 24 hours after high-risk TIA [ABCD2 ≥4] or minor ischemic stroke) reduced the absolute risk of subsequent stroke by 2% compared with aspirin alone.[92] All-cause mortality did not differ between treatment groups; clopidogrel plus aspirin was associated with a small absolute increased risk of moderate or severe extracranial bleeding (0.2%).[92] In a second meta-analysis, the risk of recurrent ischemic stroke in patients with TIA or acute ischemic stroke was significantly reduced with short-term (≤1 month; relative risk [RR] 0.53, 95% CI 0.37 to 0.78) and intermediate-term (≤3 months; RR 0.72, 95% CI 0.58 to 0.90) aspirin plus clopidogrel compared with aspirin alone.[93] Long-term combination treatment (>3 months) did not reduce risk of recurrent ischemic stroke (RR 0.81, 95% CI 0.63 to 1.04).[93] Intermediate-term (RR 2.58, 95% CI 1.19 to 5.60) and long-term (RR 1.87, 95% CI 1.36 to 2.56) combined treatment significantly increased the risk of major bleeding, but short-term treatment did not (RR 1.82, 95% CI 0.91 to 3.62).[93]

Clopidogrel is the preferred agent for patients with aspirin allergy.

Aspirin/dipyridamole: one meta-analysis found that aspirin/dipyridamole was more effective than aspirin alone for the prevention of stroke in patients with minor stroke or TIA (RR 0.77, 95% CI 0.67 to 0.89; approximate absolute risk reduction 2.3%).[88] However, subsequent meta-analyses failed to demonstrate that aspirin/dipyridamole significantly reduced stroke recurrence compared with aspirin alone in patients with acute ischemic stroke or TIA (RR 0.64, 95% CI 0.37 to 1.10, P=0.11).[89][90] Dual therapy with aspirin/dipyridamole did not appear to increase the risk of major bleeding.[90] Dipyridamole is not recommended as monotherapy.

The dual antiplatelet therapy regimen of ticagrelor plus aspirin is approved by the Food and Drug Administration (FDA) in the US to reduce the risk for stroke in patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 or high-risk TIA.The choice of adding ticagrelor or clopidogrel to aspirin should be based on patient factors (e.g., medication adherence, dose frequency).[21] In Europe, an application to the European Medicines Agency (EMA) to change the marketing authorization of ticagrelor to include the prevention of stroke in adults who have had a mild to moderate ischemic stroke or high-risk TIA was withdrawn in December 2021. Based on trial data and the company’s response to their questions, the EMA expressed concern that the benefits of short-term treatment with ticagrelor plus aspirin in preventing stroke in these patients did not clearly outweigh the risks of fatal and nonfatal bleeding. The THALES trial of 11,016 patients (none of whom received thrombolysis or thrombectomy or required anticoagulation) demonstrated that compared with aspirin alone, dual treatment with ticagrelor plus aspirin reduced the risk of disabling stroke or death within 30 days (4.0% vs. 4.7%).[83] Severe bleeding was more frequent with ticagrelor plus aspirin than with aspirin alone (0.5% vs. 0.1%), including in those with intracranial hemorrhage (0.4% vs. 0.1%). For people with recent stroke with NIHSS score of <5, ticagrelor plus aspirin for 30 days was more effective in preventing recurrent ischemic stroke than aspirin alone.[83]

Bleeding and gastrointestinal upset are common side effects of all antiplatelet therapy.

Primary options

aspirin: 50-325 mg orally once daily

OR

clopidogrel: 75 mg orally once daily

OR

aspirin: 50-325 mg orally once daily

More

and

clopidogrel: 300-600 mg orally as a loading dose, followed by 75 mg once daily

OR

aspirin/dipyridamole: 25 mg/200 mg orally twice daily

Secondary options

aspirin: 50-325 mg orally once daily

More

and

ticagrelor: 180 mg orally as a loading dose, followed by 90 mg twice daily

Plus – statin

Back
ACUTE
|
small-vessel TIA
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

Demonstrated to provide benefit acutely after cerebrovascular ischemia. Statin treatment should not be started immediately. There is consensus that it is safe to start statins after 48 hours.[43] Statin treatment should be continued in people who are already receiving statins.[43]

Statin therapy is recommended for all TIA patients barring contraindication.[71]

Guidelines recommend high-intensity statin therapy for all patients ages ≤75 years with TIA, and moderate-intensity or high-intensity statin therapy as being reasonable for patients ages >75 years with TIA after consideration of benefits, risks, and patient preference.[71]

Intensity of statin therapy is defined as: high-intensity - daily dose typically lowers low-density lipoprotein cholesterol (LDL-cholesterol) by ≥50%; moderate-intensity - daily dose typically lowers LDL-cholesterol by 30% to 49%.[71]

There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Consider – ezetimibe

Back
ACUTE
|
small-vessel TIA
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

It may be reasonable to add ezetimibe for patients with clinical atherosclerotic cardiovascular disease who still have an LDL-cholesterol level of ≥70 mg/dL (≥1.8 mmol/L) on maximally tolerated statin therapy.[21][23][112] The BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations Opens in new window​​​ There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

ezetimibe: 10 mg orally once daily

Consider – proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Back
ACUTE
|
small-vessel TIA
Consider – 

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

Alirocumab and evolocumab are approved by the FDA for the reduction of LDL-cholesterol alone or in combination with other lipid-lowering therapies.

The AHA recommends alirocumab or evolocumab for very high-risk patients including those with a history of multiple major atherosclerotic cardiovascular disease (ASCVD) events or one major ASCVD event and multiple high-risk conditions (e.g., age ≥65 years; heterozygous familial hypercholesterolemia; history of coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD events; diabetes; hypertension; chronic kidney disease; or current smoking).[21]

Alirocumab significantly reduced LDL-cholesterol levels in patients with heterozygous familial hypercholesterolemia receiving statin therapy at the maximum tolerated dose.[115] In one multicenter, randomized, double-blind, placebo-controlled trial of patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower in those who received alirocumab than in those who received placebo.[116]

Primary options

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

Plus – lifestyle modifications with or without antihypertensive therapy

Back
ACUTE
|
small-vessel TIA
|
with hypertension
Plus – 

lifestyle modifications with or without antihypertensive therapy

Treatment recommended for ALL patients in selected patient group

Patients with previously treated hypertension should be restarted on antihypertensive treatment after the first few days of the index event.[39] Patients not previously treated for hypertension who experience a TIA and have an established blood pressure (BP) ≥140/90 mmHg should be prescribed antihypertensive treatment a few days after the index event, preferably in partnership with a primary care physician.[13][39]​​ Caution is advised in lowering BP in patients with severe carotid stenosis to prevent cerebral hypoperfusion prior to carotid revascularization.[117]

Guidelines from the American Heart Association and American Stroke Association (AHA/ASA) recommend an office BP goal of <130/80 mmHg for most patients to reduce the risk of recurrent stroke and vascular events.[21] The American Academy of Neurology recommends a long-term BP target of <140/90 mmHg in patients with symptomatic intracranial atherosclerotic arterial stenosis.[23] Drug regimens should be individualized to take into account patient comorbidities, agent pharmacologic class, and patient preference.[21][23][39]

Lifestyle modifications, including salt restriction, weight loss, healthy diet, exercise, and limited alcohol consumption, are considered reasonable interventions for most people with above-normal BP.[39]​​

Plus – carotid endarterectomy or stent

Back
ACUTE
|
small-vessel TIA
|
with ≥50% carotid stenosis
Plus – 

carotid endarterectomy or stent

Treatment recommended for ALL patients in selected patient group

In patients with a TIA or nondisabling stroke within the past 6 months and ipsilateral severe (70% to 99%) carotid artery stenosis, carotid endarterectomy is recommended to reduce the risk of future stroke, provided that perioperative morbidity and mortality risk is estimated to be <6%.[21][118] Referral for carotid endarterectomy is appropriate as long as the patient is neurologically stable, with surgery within 2 weeks of the event preferred.[21][32]​​[43]​​

In patients with symptomatic carotid stenosis (i.e., TIA or nondisabling stroke), carotid artery stenting is preferred over carotid endarterectomy if the degree of stenosis is between 50% and 69% by digital subtraction angiography. This is appropriate only if perioperative risk of morbidity and mortality is <6%.

In patients with recent TIA or ischemic stroke and ipsilateral moderate (50% to 69%) carotid stenosis as documented by catheter-based imaging or noninvasive imaging, carotid endarterectomy is recommended to reduce the risk of future stroke, depending on patient-specific factors such as age, sex, and comorbidities, if the perioperative morbidity and mortality risk is estimated to be <6%.[21]

Plus – lifestyle modifications

Back
ACUTE
|
small-vessel TIA
|
with suboptimal lifestyle
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Patients with TIA who smoke are strongly advised to stop smoking. Counseling with or without drug therapy (nicotine replacement, bupropion, or varenicline) is recommended to assist in stopping smoking to reduce risk of recurrent stroke.[21] Avoidance of environmental (passive) tobacco smoke is also recommended.[21]

Patients with TIA who drink >2 alcoholic drinks a day (men) or >1 alcoholic drink a day (women) should be counseled to eliminate or reduce their consumption of alcohol to reduce stroke risk.[21]

In patients who are overweight or obese, weight loss is recommended.[21] In patients who are obese, referral to an intensive, multicomponent, behavioral lifestyle-modification program is recommended to achieve sustained weight loss.[21]

In patients with stroke or TIA who are able and willing to increase physical activity, engaging in an exercise class that includes counseling to change physical activity behavior can be beneficial for reducing cardiometabolic risk factors and increasing leisure time physical activity participation.[21] All patients who have had ischemic stroke or TIA who are capable of physical exercise should be strongly advised to participate in at least moderate intensity aerobic activity for a minimum of 10 minutes 4 times a week or vigorous-intensity aerobic activity for a minimum of 20 minutes twice a week.[21] When this is not possible, the patient's physical goals should be customized to their exercise tolerance, stage of recovery, environment, available social support, physical activity preferences, and specific impairments, activity limitations, and participation restrictions. For those who sit for long periods of uninterrupted time during the day, it may be reasonable to break up sedentary time with intervals as short as 3 minutes of standing or light exercise every 30 minutes for their cardiovascular health.[21]

It is reasonable to counsel individuals to follow a Mediterranean-type diet, typically with emphasis on monounsaturated fat, plant-based foods, and fish consumption, with either high extra virgin olive oil or nut supplementation, in preference to a low-fat diet, to reduce risk of recurrent stroke.[21] For patients with stroke and hypertension who are not currently restricting their dietary sodium intake, it is reasonable to recommend that individuals reduce their sodium intake by at least 1 g/day (2.5 g/day salt) to reduce the risk of cardiovascular disease events (including stroke).[21] Adherence to the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) dietary pattern may be helpful for secondary prevention.[121]

cardioembolic TIA

1st line – anticoagulation

Back
ACUTE
|
cardioembolic TIA
1st line – 

anticoagulation

The preferred treatment is anticoagulation. Treatment is acute and ongoing if there are irreversible cardioembolic risk factors. Anticoagulation should be started within the first 2 weeks.[95][96]

In patients with nonvalvular atrial fibrillation and stroke or TIA, oral anticoagulation (e.g., apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) is recommended to reduce the risk of recurrent stroke, regardless of whether the atrial fibrillation pattern is paroxysmal, persistent, or permanent.[21]

Direct-acting oral anticoagulants (DOACs), such as apixaban, dabigatran, edoxaban, or rivaroxaban, are recommended over a vitamin K antagonist, e.g., warfarin, in patients with stroke or TIA and atrial fibrillation who do not have moderate to severe mitral stenosis or a mechanical heart valve.[21] Large randomized trials have shown DOACs to clinically reduce the risk of thrombotic stroke with less bleeding risk compared with vitamin K antagonists.[21][97][98] DOACs have the significant advantage of fast onset, predictable dosing requirements, and eliminating the need for monitoring.[99] Disadvantages include higher drug cost and inability to reliably monitor anticoagulant effect using prothrombin time (PT), international normalized ratio (INR), or partial thromboplastin time (PTT).

Patients with valvular atrial fibrillation (i.e., moderate to severe mitral stenosis or mechanical heart valves) should be treated with warfarin. Range INR for patients on warfarin should be 2.0 to 3.0.[21] Mitral mechanical prosthetic valves require a higher INR goal of 3.0.[21] Antiplatelet therapy continues to be recommended over warfarin in patients with ischemic stroke or TIA and native aortic or nonrheumatic mitral valve disease (e.g., mitral annular calcification or mitral valve prolapse) who do not have atrial fibrillation or another indication for anticoagulation.[21]

Dabigatran is contraindicated in people with mechanical heart valves. Apixaban, edoxaban, and rivaroxaban have not been studied in patients with prosthetic heart valves and are not recommended in these patients.

Isolated patent foramen ovale (PFO) likely warrants antiplatelet therapy alone. Guidelines from the American Academy of Neurology state that evidence is insufficient to establish whether anticoagulation is equivalent or superior to antiplatelet therapy for patients with PFO.[102] Patients with cryptogenic stroke can remain on antiplatelet treatment while decisions are made about PFO closure.[35] The American Heart Association (AHA) recommends that closure of a PFO should be considered for patients with a nonlacunar stroke, particularly for those ages 18-60 years found to have high-risk features such as an atrial septal aneurysm and larger shunt size.[21] Evidence specific to TIA is scarce, as patients with TIA have been excluded from most PFO closure trials.[103] The Society for Cardiovascular Angiography and Interventions recommends against PFO closure in patients with TIA without prior PFO-associated stroke, but states that closure could be considered in patients with recurrent, high-probability TIAs who place a high value on the uncertain benefits of closure and low value on potential procedural risks.[104]

The dose of dabigatran, rivaroxaban, apixaban, and edoxaban should be adjusted according to the level of renal impairment.

A validated scoring system should be used to assess the bleeding risk of the patient; if high, the patient should be followed up more closely. See New-onset atrial fibrillation.

Primary options

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

More

OR

dabigatran etexilate: 150 mg orally twice daily

OR

rivaroxaban: 20 mg orally once daily

OR

apixaban: 5 mg orally twice daily

OR

edoxaban: 60 mg orally once daily

Plus – statin

Back
ACUTE
|
cardioembolic TIA
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

Demonstrated to provide benefit acutely after cerebrovascular ischemia. Statin treatment should not be started immediately. There is consensus that it is safe to start statins after 48 hours.[43] Statin treatment should be continued in people who are already receiving statins.[43]

Guidelines recommend high-intensity statin therapy for all patients ages ≤75 years with TIA, and moderate-intensity or high-intensity statin therapy as being reasonable for patients ages >75 years with TIA after consideration of benefits, risks, and patient preference.[71]

Intensity of statin therapy is defined as: high-intensity - daily dose typically lowers low-density lipoprotein cholesterol (LDL-cholesterol) by ≥50%; moderate-intensity - daily dose typically lowers LDL-cholesterol by 30% to 49%.[71]

There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Consider – ezetimibe

Back
ACUTE
|
cardioembolic TIA
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

It may be reasonable to add ezetimibe for patients with accompanying clinical atherosclerotic cardiovascular disease who still have an LDL-cholesterol level of ≥70 mg/dL (≥1.8 mmol/L) on maximally tolerated statin therapy.[21][23][112] The BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations Opens in new window​​ There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

ezetimibe: 10 mg orally once daily

Consider – proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Back
ACUTE
|
cardioembolic TIA
Consider – 

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

Alirocumab and evolocumab are approved by the Food and Drug Administration for the reduction of LDL-cholesterol alone or in combination with other lipid-lowering therapies.

It may be reasonable to add alirocumab or evolocumab for patients with accompanying clinical atherosclerotic cardiovascular disease (ASCVD).

The AHA recommends alirocumab or evolocumab for very high-risk patients including those with a history of multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions (e.g., age ≥65 years; heterozygous familial hypercholesterolemia; history of coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD events; diabetes; hypertension; chronic kidney disease; or current smoking).[21]

Alirocumab significantly reduced LDL-cholesterol levels in patients with heterozygous familial hypercholesterolemia receiving statin therapy at the maximum tolerated dose.[115] In one multicenter, randomized, double-blind, placebo-controlled trial of patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower in those who received alirocumab than in those who received placebo.[116]

Primary options

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

2nd line – antiplatelet therapy

Back
ACUTE
|
cardioembolic TIA
2nd line – 

antiplatelet therapy

Aspirin or aspirin plus clopidogrel should be used only if anticoagulation is contraindicated.[100] Antiplatelet therapy is inferior to anticoagulation therapy in stroke prevention for patients with atrial fibrillation but may be the only option for a patient with a contraindication to anticoagulants.[101]

Antiplatelet therapy is also considered reasonable for TIA associated with a patent foramen ovale (PFO).[21]​​

Isolated PFO likely warrants antiplatelet therapy alone. Guidelines from the American Academy of Neurology state that evidence is insufficient to establish whether anticoagulation is equivalent or superior to antiplatelet therapy for patients with PFO.[102] Patients with cryptogenic stroke can remain on antiplatelet treatment while decisions are made about PFO closure.[35]

The AHA recommends that closure of a PFO should be considered for patients with a nonlacunar stroke, particularly for those ages 18-60 years found to have high-risk features such as an atrial septal aneurysm and larger shunt size.[21] Evidence specific to TIA is scarce, as patients with TIA have been excluded from most PFO closure trials.[103] The Society for Cardiovascular Angiography and Interventions recommends against PFO closure in patients with TIA without prior PFO-associated stroke, but states that closure could be considered in patients with recurrent, high-probability TIAs who place a high value on the uncertain benefits of closure and low value on potential procedural risks.[104]

A validated scoring system should be used to assess the bleeding risk of the patient; if high, the patient should be followed up more closely. See New-onset atrial fibrillation.

Primary options

aspirin: 325 mg orally once daily

Secondary options

aspirin: 325 mg orally once daily

and

clopidogrel: 75 mg orally once daily

Plus – statin

Back
ACUTE
|
cardioembolic TIA
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

Should be considered in all patients with a cardioembolic TIA with other atherosclerotic risk factors.[71] Statin treatment should not be started immediately. There is consensus that it is safe to start statins after 48 hours.[43] Statin treatment should be continued in people who are already receiving statins.[43]

Guidelines recommend high-intensity statin therapy for all patients ages ≤75 years with TIA, and moderate-intensity or high-intensity statin therapy as being reasonable for patients ages >75 years with TIA after consideration of benefits, risks, and patient preference.[71]

Intensity of statin therapy is defined as: high-intensity - daily dose typically lowers LDL-cholesterol by ≥50%; moderate-intensity - daily dose typically lowers LDL-cholesterol by 30% to 49%.[71]

There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Consider – ezetimibe

Back
ACUTE
|
cardioembolic TIA
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

It may be reasonable to add ezetimibe for patients with accompanying clinical atherosclerotic cardiovascular disease who still have an LDL-cholesterol level of ≥70 mg/dL (≥1.8 mmol/L) on maximally tolerated statin therapy.[21][23][112] The BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations Opens in new window​​ There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

ezetimibe: 10 mg orally once daily

Consider – proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Back
ACUTE
|
cardioembolic TIA
Consider – 

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

Alirocumab and evolocumab are approved by the FDA for the reduction of LDL-cholesterol alone or in combination with other lipid-lowering therapies.

The AHA recommends alirocumab or evolocumab for very high-risk patients including those with a history of multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions (e.g., age ≥65 years; heterozygous familial hypercholesterolemia; history of coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD events; diabetes; hypertension; chronic kidney disease; or current smoking).[21]

Alirocumab significantly reduced LDL-cholesterol levels in patients with heterozygous familial hypercholesterolemia receiving statin therapy at the maximum tolerated dose.[115] In one multicenter, randomized, double-blind, placebo-controlled trial of patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower in those who received alirocumab than in those who received placebo.[116]

Primary options

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

Plus – lifestyle modifications with or without antihypertensive therapy

Back
ACUTE
|
cardioembolic TIA
|
with hypertension
Plus – 

lifestyle modifications with or without antihypertensive therapy

Treatment recommended for ALL patients in selected patient group

Patients with previously treated hypertension should be restarted on antihypertensive treatment after the first few days of the index event.[39] Patients not previously treated for hypertension who experience a TIA and have an established blood pressure (BP) of 140/90 mmHg or higher should be prescribed antihypertensive treatment a few days after the index event, preferably in partnership with a primary care physician.[13][39]​​​ Caution is advised in lowering BP in patients with severe carotid stenosis to prevent cerebral hypoperfusion prior to carotid revascularization.[117]

Lifestyle modifications, including salt restriction, weight loss, healthy diet, exercise, and limited alcohol consumption, are considered reasonable interventions for most people with above-normal BP.[39]​​

Diuretics, angiotensin-II receptor antagonists, and ACE inhibitors have all been studied and found effective in reducing stroke risk, but the optimal agent or combination has not been determined. [ Cochrane Clinical Answers logo ] ​ Drug regimens should be individualized to take into account patient comorbidities, agent pharmacologic class, and patient preference.[21][23][39]

The goal BP should be individualized for each patient.[21]​​

Plus – lifestyle modifications

Back
ACUTE
|
cardioembolic TIA
|
with suboptimal lifestyle
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Patients with TIA who smoke are strongly advised to stop smoking. Counseling with or without drug therapy (nicotine replacement, bupropion, or varenicline) is recommended to assist in stopping smoking to reduce risk of recurrent stroke.[21] Avoidance of environmental (passive) tobacco smoke is also recommended.[21]

Patients with TIA who drink >2 alcoholic drinks a day (men) or >1 alcoholic drink a day (women) should be counseled to eliminate or reduce their consumption of alcohol to reduce stroke risk.[21]

In patients who are overweight or obese, weight loss is recommended.[21] In patients who are obese, referral to an intensive, multicomponent, behavioral lifestyle-modification program is recommended to achieve sustained weight loss.[21]

In patients with stroke or TIA who are able and willing to increase physical activity, engaging in an exercise class that includes counseling to change physical activity behavior can be beneficial for reducing cardiometabolic risk factors and increasing leisure time physical activity participation.[21] All patients who have had ischemic stroke or TIA who are capable of physical exercise should be strongly advised to participate in at least moderate intensity aerobic activity for a minimum of 10 minutes 4 times a week or vigorous-intensity aerobic activity for a minimum of 20 minutes twice a week.[21] When this is not possible, the patient's physical goals should be customized to their exercise tolerance, stage of recovery, environment, available social support, physical activity preferences, and specific impairments, activity limitations, and participation restrictions. For those who sit for long periods of uninterrupted time during the day, it may be reasonable to break up sedentary time with intervals as short as 3 minutes of standing or light exercise every 30 minutes for their cardiovascular health.[21]

It is reasonable to counsel individuals to follow a Mediterranean-type diet, typically with emphasis on monounsaturated fat, plant-based foods, and fish consumption, with either high extra virgin olive oil or nut supplementation, in preference to a low-fat diet, to reduce risk of recurrent stroke.[21] For patients with stroke and hypertension who are not currently restricting their dietary sodium intake, it is reasonable to recommend that individuals reduce their sodium intake by at least 1 g/day (2.5 g/day salt) to reduce the risk of cardiovascular disease events (including stroke).[21] Adherence to the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) dietary pattern may be helpful for secondary prevention.[121]

stenosis of a major intracranial artery

1st line – antiplatelet therapy

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ACUTE
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stenosis of a major intracranial artery
1st line – 

antiplatelet therapy

In patients with stroke or TIA (within 30 days) attributable to severe stenosis (70% to 99%) of a major intracranial artery (i.e., in the distribution of the intracranial carotid, intradural vertebral, basilar, and anterior/middle/posterior cerebral arteries), the addition of clopidogrel to aspirin for up to 90 days is reasonable to further reduce recurrent stroke risk in patients who have low risk of hemorrhagic transformation.[21][23]

The dual antiplatelet therapy regimen of ticagrelor plus aspirin is approved by the Food and Drug Administration (FDA) in the US to reduce the risk for stroke in patients with acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 or high-risk TIA. The choice of adding ticagrelor or clopidogrel to aspirin should be based on patient factors (e.g., medication adherence, dose frequency).[21] In patients with minor stroke or high-risk TIA within 24 hours and concomitant ipsilateral >30% stenosis of a major intracranial artery, the addition of ticagrelor to aspirin for up to 30 days might be considered to further reduce recurrent stroke risk.[21] In Europe, an application to the European Medicines Agency (EMA) to change the marketing authorization of ticagrelor to include the prevention of stroke in adults who have had a mild to moderate ischemic stroke or high-risk TIA was withdrawn in December 2021. Based on trial data and the company's response to their questions, the EMA expressed concern that the benefits of short-term treatment with ticagrelor plus aspirin in preventing stroke in these patients did not clearly outweigh the risks of fatal and nonfatal bleeding.

In patients with TIA caused by 50% to 69% stenosis of a major intracranial artery, aspirin is recommended in preference to warfarin to reduce the risk of recurrent ischemic stroke and vascular death.[21]

Primary options

aspirin: 50-325 mg orally once daily

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and

clopidogrel: 75 mg orally once daily

Secondary options

aspirin: 50-325 mg orally once daily

More

and

ticagrelor: 90 mg orally twice daily

Plus – statin

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ACUTE
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stenosis of a major intracranial artery
Plus – 

statin

Treatment recommended for ALL patients in selected patient group

Demonstrated to provide benefit acutely after cerebrovascular ischemia. One meta-analysis showed that prescribing statin at stroke onset is associated with reduced mortality and improved functional outcome.[122] However, UK guidance recommends that statins should be started only after 48 hours. Statin treatment should be continued in people with acute stroke who are already receiving statins.[43]

Statin therapy is recommended for all TIA patients barring contraindication.[71]

Guidelines recommend high-intensity statin therapy for all patients ages ≤75 years with TIA, and moderate-intensity or high-intensity statin therapy as being reasonable for patients ages >75 years with TIA after consideration of benefits, risks, and patient preference.[71]

Intensity of statin therapy is defined as: high-intensity - daily dose typically lowers low-density lipoprotein cholesterol (LDL-cholesterol) by ≥50%; moderate-intensity - daily dose typically lowers LDL-cholesterol by 30% to 49%.[71]

There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

High-intensity statin

atorvastatin: 40-80 mg orally once daily

OR

High-intensity statin

rosuvastatin: 20-40 mg orally once daily

OR

Moderate-intensity statin

atorvastatin: 10-20 mg orally once daily

OR

Moderate-intensity statin

rosuvastatin: 5-10 mg orally once daily

OR

Moderate-intensity statin

simvastatin: 20-40 mg orally once daily; increased risk of myopathy with 80 mg/day dose

OR

Moderate-intensity statin

pravastatin: 40-80 mg orally once daily

OR

Moderate-intensity statin

lovastatin: 40-80 mg orally (immediate-release) once daily

OR

Moderate-intensity statin

fluvastatin: 40 mg orally (immediate-release) twice daily; 80 mg orally (extended-release) once daily

OR

Moderate-intensity statin

pitavastatin: 1-4 mg orally once daily

Consider – ezetimibe

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ACUTE
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stenosis of a major intracranial artery
Consider – 

ezetimibe

Treatment recommended for SOME patients in selected patient group

It may be reasonable to add ezetimibe for patients with clinical atherosclerotic cardiovascular disease who still have an LDL-cholesterol level of ≥70 mg/dL (≥1.8 mmol/L) on maximally tolerated statin therapy.[21][23][112] The BMJ: PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations Opens in new window​​ There is evidence that the rate of recurrent cardiovascular events or stroke is lower in patients whose LDL-cholesterol is controlled to <70 mg/dL (<1.81 mmol/L) compared with those with LDL-cholesterol between 90 mg/dL (2.33 mmol/L) and 110 mg/dL (2.85 mmol/L).[111]

Primary options

ezetimibe: 10 mg orally once daily

Consider – proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

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ACUTE
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stenosis of a major intracranial artery
Consider – 

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Treatment recommended for SOME patients in selected patient group

Alirocumab and evolocumab are approved by the FDA for the reduction of LDL-cholesterol alone or in combination with other lipid-lowering therapies.

The American Heart Association (AHA) recommends alirocumab or evolocumab for very high-risk patients including those with a history of multiple major atherosclerotic cardiovascular disease (ASCVD) events or one major ASCVD event and multiple high-risk conditions (e.g., age ≥65 years; heterozygous familial hypercholesterolemia; history of coronary artery bypass surgery or percutaneous coronary intervention outside of the major ASCVD events; diabetes; hypertension; chronic kidney disease; or current smoking).[21]

Alirocumab significantly reduced LDL-cholesterol levels in patients with heterozygous familial hypercholesterolemia receiving statin therapy at the maximum tolerated dose.[115] In one multicenter, randomized, double-blind, placebo-controlled trial of patients who had a previous acute coronary syndrome and who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower in those who received alirocumab than in those who received placebo.[116]

Primary options

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

Plus – lifestyle modifications with or without antihypertensive therapy

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ACUTE
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stenosis of a major intracranial artery
|
with hypertension
Plus – 

lifestyle modifications with or without antihypertensive therapy

Treatment recommended for ALL patients in selected patient group

Patients with previously treated hypertension should be restarted on antihypertensive treatment after the first few days of the index event.[39] Patients not previously treated for hypertension who experience a TIA and have an established blood pressure (BP) of 140/90 mmHg or higher should be prescribed antihypertensive treatment a few days after the index event, preferably in partnership with a primary care physician.[13][39]​​​ Caution is advised in lowering BP in patients with severe carotid stenosis to prevent cerebral hypoperfusion prior to carotid revascularization.[117]

Lifestyle modifications, including salt restriction, weight loss, healthy diet, exercise, and limited alcohol consumption, are considered reasonable interventions for most people with above-normal BP.[39]​​

Diuretics, angiotensin-II receptor antagonists, and ACE inhibitors have all been studied and found effective in reducing stroke risk, but the optimal agent or combination has not been determined. [ Cochrane Clinical Answers logo ] ​ Drug regimens should be individualized to take into account patient comorbidities, agent pharmacologic class, and patient preference.[21][23][39]

The goal BP should be individualized for each patient.[21]​ Guidelines from the American Heart Association and American Stroke Association recommend an office BP goal of <130/80 mmHg for most patients to reduce the risk of recurrent stroke and vascular events.[21]

Plus – lifestyle modifications

Back
ACUTE
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stenosis of a major intracranial artery
|
with suboptimal lifestyle
Plus – 

lifestyle modifications

Treatment recommended for ALL patients in selected patient group

Patients with TIA who smoke are strongly advised to stop smoking. Counseling with or without drug therapy (nicotine replacement, bupropion, or varenicline) is recommended to assist in stopping smoking to reduce risk of recurrent stroke.[21] Avoidance of environmental (passive) tobacco smoke is also recommended.[21]

Patients with TIA who drink >2 alcoholic drinks a day (men) or >1 alcoholic drink a day (women) should be counseled to eliminate or reduce their consumption of alcohol to reduce stroke risk.[21]

In patients who are overweight or obese, weight loss is recommended.[21] In patients who are obese, referral to an intensive, multicomponent, behavioral lifestyle-modification program is recommended to achieve sustained weight loss.[21]

In patients with stroke or TIA who are able and willing to increase physical activity, engaging in an exercise class that includes counseling to change physical activity behavior can be beneficial for reducing cardiometabolic risk factors and increasing leisure time physical activity participation.[21] All patients who have had ischemic stroke or TIA who are capable of physical exercise should be strongly advised to participate in at least moderate intensity aerobic activity for a minimum of 10 minutes 4 times a week or vigorous-intensity aerobic activity for a minimum of 20 minutes twice a week.[21] When this is not possible, the patient's physical goals should be customized to their exercise tolerance, stage of recovery, environment, available social support, physical activity preferences, and specific impairments, activity limitations, and participation restrictions. For those who sit for long periods of uninterrupted time during the day, it may be reasonable to break up sedentary time with intervals as short as 3 minutes of standing or light exercise every 30 minutes for their cardiovascular health.[21]

It is reasonable to counsel individuals to follow a Mediterranean-type diet, typically with emphasis on monounsaturated fat, plant-based foods, and fish consumption, with either high extra virgin olive oil or nut supplementation, in preference to a low-fat diet, to reduce risk of recurrent stroke.[21] For patients with stroke and hypertension who are not currently restricting their dietary sodium intake, it is reasonable to recommend that individuals reduce their sodium intake by at least 1 g/day (2.5 g/day salt) to reduce the risk of cardiovascular disease events (including stroke).[21] Adherence to the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) dietary pattern may be helpful for secondary prevention.[121]

mechanical heart valves or rheumatic heart disease already on therapeutic anticoagulation

1st line – aspirin plus continued warfarin

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ACUTE
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mechanical heart valves or rheumatic heart disease already on therapeutic anticoagulation
1st line – 

aspirin plus continued warfarin

Combination therapy (anticoagulant and antiplatelet therapy) is recommended in patients with a mechanical mitral valve and a history of ischemic stroke or TIA before valve replacement to reduce the risk of thrombosis and recurrent stroke or TIA.[21]

Routine combination anticoagulant and antiplatelet therapy is not recommended for cardioembolic TIAs due to atrial fibrillation or rheumatic valve disease.[21]

Dabigatran is contraindicated in people with mechanical heart valves. Apixaban, edoxaban, and rivaroxaban have not been studied in patients with prosthetic heart valves and are not recommended in these patients.

Primary options

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

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and

aspirin: 81 mg orally once daily

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