AHA, ASA guidelines for stroke

Template:AHA, ASA stroke guidelines Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Tarek Nafee, M.D. [2]

2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association

DIAGNOSTIC EVALUATION FOR SECONDARY STROKE PREVENTION

Class I

"1.     In patients suspected of having a stroke or TIA, an ECG is recommended to screen for atrial fibrillation (AF) and atrial flutter and to assess for other concomitant cardiac conditions. (Level of evidence: B-R)"

"2.      In patients with ischemic stroke or TIA, a diagnostic evaluation is recommended for gaining insights into the etiology of and planning optimal strategies for preventing recurrent stroke, with testing completed or underway within 48 hours of onset of stroke symptoms (Level of evidence: B-NR) "

"3.     In patients with symptomatic anterior circulation cerebral infarction or TIA who are candidates for revascularization, noninvasive cervical carotid imaging with carotid ultrasonography, CT angiography (CTA), or magnetic resonance angiography (MRA) is recommended to screen for stenosis (Level of evidence: B-NR) "

"4.     In patients suspected of having a stroke or TIA, CT or MRI of the brain is recommended to confirm the diagnosis of symptomatic ischemic cerebral vascular disease (Level of evidence: B-NR) "

"5.     In patients with a confirmed diagnosis of symptomatic ischemic cerebrovascular disease, blood tests, including complete blood count, prothrombin time, partial thromboplastin time, glucose, HbA1c, creatinine, and fasting or non-fasting lipid profile, are recommended to gain insight into risk factors for stroke and to inform therapeutic goals (Level of evidence: B-NR) "

Class IIa

" 6.     In patients with cryptogenic stroke, echocardiography with or without contrast is reason-able to evaluate for possible cardiac sources of or transcardiac pathways for cerebral embolism (Level of Evidence B-R)".

'' 7.     In patients with cryptogenic stroke who do not have a contraindication to anticoagulation, long-term rhythm monitoring with mobile cardiac outpatient telemetry, implantable loop recorder, or other approach is reasonable to detect intermittent AF. (Level of Evidence B R)''

'' 8.    In patients suspected of having an ischemic stroke, if CT or MRI does not demonstrate symptomatic cerebral infarct, follow-up CT or MRI of the brain is reasonable to confirm a diagnosis. (Level of Evidence B- NR)''

'' 9.       In patients suspected of having had a TIA, if the initial head imaging (CT or MRI) does not demonstrate a symptomatic cerebral infarct, follow-up MRI is reasonable to predict the risk of early stroke and to support the diagnosis. (Level of Evidence B- NR)''

'' 10.    In patients with cryptogenic stroke, tests for inherited or acquired hypercoagulable state, bloodstream or cerebral spinal fluid infections, infections that can cause central nervous system (CNS) vasculitis (eg, HIV and syphilis), drug use (eg, cocaine and amphetamines), and markers of systemic inflammation and genetic tests for inherited diseases associated with stroke are reason-able to perform as clinically indicated to identify contributors to or relevant risk factors for stroke. (Level of Evidence C-LD)''

'' 11.     In patients with ischemic stroke or TIA, noninvasive imaging of the intracranial large arteries and imaging of the extracranial vertebro-basilar arterial system with MRA or CTA can be effective to identify atherosclerotic disease, dissection, moyamoya, or other etiologically relevant vasculopathies. (Level of Evidence C-LD)''

Class IIb

" 12.    In patients with ischemic stroke and a treatment plan that includes anticoagulant therapy, CT or MRI of the brain before therapy is started may be considered to assess for hemorrhagic transformation and final size of infarction (Level of Evidence B-NR)".

'' 13.       In patients with ESUS, transesophageal echocardiography (TEE), cardiac CT, or cardiac MRI might be reasonable to identify possible cardioaortic sources of or transcardiac pathways for cerebral embolism. (Level of Evidence C-LD)''

'' 14.      In patients with ischemic stroke or TIA in whom patent foramen ovale (PFO) closure would be contemplated, TCD (transcranial Doppler) with embolus detection might be reasonable to screen for right-to-left shun. (Level of Evidence C LD)''

NUTRITION

Class IIa

" 1.     In patients with stroke and TIA, it is reasonable to counsel individuals to follow a Mediterranean type diet, typically with empha-sis 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 (Level of Evidence B-R)".

'' 2.       In patients with stroke or TIA 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 1g/d sodium (2.5 g/d salt) to reduce the risk of cardiovascular disease (CVD) events (including stroke). (Level of Evidence B R)''

PHYSICAL ACTIVITY

Class I

"1.        In patients with stroke or TIA who are capable of physical activity, engaging in at least moderate-intensity aerobic activity for a minimum of 10 min-utes 4 times a week or vigorous-intensity aerobic activity for a minimum of 20 minutes twice a week is indicated to lower the risk of recurrent stroke and the composite cardiovascular end point of recurrent stroke, MI, or vascular death. (Level of evidence: C-LD)"

Class IIa

" 2.          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. (Level of Evidence B-R)".

'' 3.           In patients with deficits after a stroke that impair their ability to exercise, supervision of an exercise program by a health care professional such as a physical therapist or cardiac rehabilitation professional, in addition to routine rehabilitation, can be beneficial for secondary stroke prevention. (Level of Evidence C-EO)''

Class IIb

" 4.       In individuals with stroke or TIA who sit for long periods of uninterrupted time during the day, it may be reasonable to recommend breaking up sedentary time with intervals as short as 3 minutes of standing or light exercise every 30 minutes for their cardiovascular health (Level of Evidence B-NR)".

SMOKING CESSATION

Class I

"1.         In patients with stroke or TIA who smoke tobacco, counseling with or without drug therapy (nicotine replacement, bupropion, or varenicline) is recommended to assist in quitting smoking. (Level of evidence: A)"

"2.         Patients with stroke or TIA who continue to smoke tobacco should be advised to stop smoking (and, if unable, to reduce their daily smoking) to lower the risk of recurrent stroke (Level of evidence: B-NR) "

"3.       In patients with stroke or TIA. avoidance of environmental (passive) tobacco smoke is recommended to reduce the risk of recurrent stroke. (Level of evidence: B-NR) "

SUBSTANCE USE

Class I

"1.           Patients with ischemic stroke or TIA who drink >2 alcoholic drinks a day for men or >1 alcoholic drink a day for women should be counseled to eliminate or reduce their consumption of alcohol to reduce stroke risk. (Level of evidence: B-NR)"

"2.            In patients with stroke or TIA who use stimulants (eg, amphetamines, amphetamine derivatives, cocaine, or khat) and in patients with infective endocarditis (IE) in the context of intravenous drug use, it is recommended that health care providers inform them that this behavior is a health risk and counsel them to stop. (Level of evidence: C-EO) "

"3.          In patients with stroke or TIA who have a substance use disorder (drugs or alcohol), specialized services are recommended to help manage this dependenc. (Level of evidence: C-EO) "

HYPERTENTION

Class I

"1.           Patients with ischemic stroke or TIA who drink >2 alcoholic drinks a day for men or >1 alco-holic drink a day for women should be coun-seled to eliminate or reduce their consumption of alcohol to reduce stroke risk. (Level of evidence: A)"

"2.            In patients with hypertension who experience a stroke or TIA, an office BP goal of <130/80 mm Hg is recommended for most patients to reduce the risk of recurrent stroke and vascular events. (Level of evidence: B-R) "

"3.          In patients with hypertension who experience a stroke or TIA, individualized drug regimens that take into account patient comorbidities, agent pharmacological class, and patient preference are recommended to maximize drug efficacy (Level of evidence: B-NR) "

Class IIa

" 4.              In patients with no history of hypertension who experience a stroke or TIA and have an aver-age office BP of ≥130/80 mm Hg, antihypertensive medication treatment can be beneficial to reduce the risk of recurrent stroke, ICH, and other vascular events (Level of Evidence B-R)".

Treatment

Class I

"1. In patients with ischemic stroke with no known coronary heart disease, no major cardiac sources of embolism, and LDL cholesterol (LDL-C) >100 mg/dL, atorvastatin 80 mg daily is indicated to reduce risk of stroke recurrence. (Level of evidence: A)"

"2.  In patients with ischemic stroke or TIA and ath-erosclerotic disease (intracranial, carotid, aortic, or coronary), lipid-lowering therapy with a statin and also ezetimibe, if needed, to a goal LDL-C of <70 mg/dL is recommended to reduce the risk of major cardiovascular events. (Level of evidence: A) "

Monitoring

Class I

"1. In patients with stroke or TIA and hyperlipidemia, patients’ adherence to changes in lifestyle and the effects of LDL-C–lowering medication should be assessed by measurement of fasting lipids and appropriate safety indicators 4 to 12 weeks after statin initiation or dose adjustment and every 3 to 12 months thereafter, based on the need to assess adherence or safety. (Level of evidence: A)"

Treatment of Hypertriglyceridemia

Class IIa

" 1. In patients with ischemic stroke or TIA, with fasting triglycerides 135 to 499 mg/dL and LDL-C of 41 to 100 mg/dL, on moderate- or high-intensity statin therapy, with HbA1c <10%, and with no history of pancreatitis, AF, or severe heart failure, treatment with icosapentethyl (IPE) 2 g twice a day is reasonable to reduce risk of recurrent stroke. (Level of Evidence B-R)".

'' 2. In patients with severe hypertriglyceridemia (ie, fasting triglycerides ≥500 mg/dL [≥5.7 mmol/L]), it is reasonable to identify and address causes of hypertriglyceridemia and, if triglycerides are persistently elevated or increasing, to further reduce triglycerides in order to lower the risk of ASCVD events by the implementation of a very low-fat diet, avoidance of refined carbohydrates and alcohol, consumption of omega-3 fatty acids, and, if necessary to prevent acute pancreatitis, fibrate therapy. (Level of Evidence B-NR)''

Glucose

Class I

"1.  In patients with an ischemic stroke or TIA who also have diabetes, the goal for glycemic control should be individualized based on the risk for adverse events, patient characteristics, and preferences, and, for most patients, especially those <65 years of age and without life-limiting comorbid illness, achieving a goal of HbA1c ≤7% is recommended to reduce the risk for microvascular complications. (Level of evidence: A)"

"2. In patients with an ischemic stroke or TIA who also have diabetes, treatment of diabetes should include glucose-lowering agents with proven cardiovascular benefit to reduce the risk for future major adverse cardiovas-cular events (ie, stroke, MI, cardiovascular death) (Level of evidence: B-R) "

"3. In patients with an ischemic stroke or TIA who also have diabetes, multidimensional care (ie, lifestyle counseling, medical nutritional therapy, diabetes self-management education, support, and medication) is indicated to achieve glycemic goals and to improve stroke risk factors (Level of evidence: C-EO) "

Class IIa

" 4. In patients with prediabetes and ischemic stroke or TIA, lifestyle optimization (ie, healthy diet, regular physical activity, and smoking cessation) can be beneficial for the preven-tion of progression to diabetes (Level of Evidence B-R)".

'' 5.   In patients with TIA or ischemic stroke, it is reasonable to screen for prediabetes/dia-betes using HbA1c which, among available methods (HbA1c, fasting plasma glucose, oral glucose tolerance), has the advantage of convenience because it does not require fasting and is measured in a single blood sample. (Level of Evidence C-EO)''

Class IIb

" 6.   In patients with an ischemic stroke or TIA who also have diabetes, the usefulness of achieving intensive glucose control (ie, HbA1c ≤7%) beyond the acute phase of the ischemic event for prevention of recurrent stroke is unknown. (Level of Evidence B-R)".

'' 7.  In patients with prediabetes and ischemic stroke or TIA, particularly those with a body mass index (BMI) ≥35 kg/mP2, ≥35 kg/m2those <60 years of age, or women with a history of gestational diabetes, metformin may be beneficial to control blood sugar and to prevent progression to diabetes (Level of Evidence B-R)''

'' 8. In patients ≤6 months after TIA or ischemic stroke with insulin resistance, HbA1c <7.0%, and without heart failure or bladder cancer, treatment with pioglitazone may be consid-ered to prevent recurrent stroke (Level of Evidence B-R)''

Obesity

Class I

"1. In patients with ischemic stroke or TIA and who are overweight or obese, weight loss is recommended to improve the ASCVD risk factor profile. (Level of evidence: B-R)"

"2. In patients with ischemic stroke or TIA who are obese, referral to an intensive, multicompo-nent, behavioral lifestyle-modification program is recommended to achieve sustained weight loss (Level of evidence: B-R) "

"3. In patients with ischemic stroke or ASCVD, calculation of BMI is recommended at the time of their event and annually thereafter, to screen for and to classify obesity. (Level of evidence: C-EO) "

Obstructive sleep apnea

Class IIa

" 1. In patients with an ischemic stroke or TIA and OSA, treatment with positive airway pressure (eg, continuous positive airway pressure [CPAP]) can be beneficial for improved sleep apnea, BP, sleepiness, and other apnea-related outcomes. (Level of Evidence B-R)".

Class IIb

" 2. In patients with an ischemic stroke or TIA, an evaluation for OSA may be considered for diagnosing sleep apnea (Level of Evidence B-R)".

Management of Intracranial Large Artery Atherosclerosis. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association

Antithombotic Therapy:

Class I

"1. In patients with a stroke or TIA caused by 50% to 99% stenosis of a major intracranial artery, aspirin 325 mg/d is recommended in preference to warfarin to reduce the risk of recurrent ischemic stroke and vascular death. (Level of evidence: B-R)"

Class IIa

" 2.     In patients with recent stroke or TIA (within 30 days) attributable to severe stenosis (70%–99%) of a major intracranial artery, the addition of clopidogrel 75 mg/d to aspirin for up to 90 days is reasonable to further reduce recurrent stroke risk. (Level of Evidence B-NR)".

Class IIb

" 3.      In patients with recent (within 24 hours) minor stroke or high-risk TIA and concomitant ipsilateral >30% stenosis of a major intracranial artery, the addition of ticagrelor 90 mg twice a day to aspirin for up to 30 days might be considered to further reduce recurrent stroke risk. (Level of Evidence B-R)".

'' 4.     In patients with stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery, the addition of cilostazol 200 mg/day to aspirin or clopidogrel might be considered to reduce recurrent stroke risk. (Level of Evidence C-LD)''

'' 5. In patients ≤6 months after TIA or ischemic stroke with insulin resistance, HbA1c <7.0%, and without heart failure or bladder cancer, treatment with pioglitazone may be consid-ered to prevent recurrent stroke (Level of Evidence C-EO)''

Risk factor Managment:

Class I

"6. In patients with a stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery, maintenance of SBP below 140 mm Hg, high-intensity statin therapy, and at least moderate physical activity are recom-mended to prevent recurrent stroke and vascular events. (Level of evidence: B-NR)"

Angioplasty and Stenting

Class IIb

" 7. In patients with severe stenosis (70%-99%) of a major intracranial artery and actively progressing symptoms or recurrent TIA or stroke after the institution of aspirin and clopidogrel therapy, achievement of SBP <140  mm Hg, and high-intensity statin therapy (so-called medical failures), the usefulness of angioplasty alone or stent placement to prevent ischemic stroke in the territory of the stenotic artery is unknown (Level of Evidence C-LD)".

Class III (Harm)

"8. In patients with stroke or TIA attributable to severe stenosis (70%–99%) of a major intracranial artery, angioplasty and stenting should not be performed as an initial treatment, even for patients who were taking an antithrombotic agent at the time of the stroke or TIA. (Level of Evidence:A) "

" 9.      In patients with a stroke or TIA attributable to moderate stenosis (50%–69%) of a major intracranial artery, angioplasty or stenting is associated with excess morbidity and mortality compared with medical management alone. (Level of Evidence B-NR)".

Other Procedures

Class III (No Benefit)

"10. In patients with stroke or TIA attributable to 50% to 99% stenosis or occlusion of a major intracranial artery, extracranial-intracra-nial bypass surgery is not recommended (Level of Evidence:B-R) "

EXTRACRANIAL CAROTID STENOSIS

Class I

"1.  In patients with a TIA or nondisabling ischemic stroke within the past 6 months and ipsilateral severe (70%–99%) carotid artery stenosis, carotid endarterectomy (CEA) is recommended to reduce the risk of future stroke, provided that perioperative morbidity and mortality risk is estimated to be <6%. (Level of evidence: A)"

"2.   In patients with ischemic stroke or TIA and symptomatic extracranial carotid stenosis who are scheduled for carotid artery stent-ing (CAS) or CEA, procedures should be performed by operators with established periprocedural stroke and mortality rates of <6% to reduce the risk of surgical adverse events.(Level of evidence: A) "

"3. In patients with carotid artery stenosis and a TIA or stroke, intensive medical therapy, with antiplatelet therapy, lipid-lowering therapy, and treatment of hypertension, is recom-mended to reduce stroke risk (Level of evidence: A) "

"4. In patients with recent TIA or ischemic stroke and ipsilateral moderate (50%–69%) carotid steno-sis as documented by catheter-based imaging or noninvasive imaging, CEA 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% (Level of evidence: B-R) "

Class IIa

" 5.      In patients ≥70 years of age with stroke or TIA in whom carotid revascularization is being considered, it is reasonable to select CEA over CAS to reduce the periprocedural stroke rate (Level of Evidence B-R)".

'' 6.      In patients in whom revascularization is planned within 1 week of the index stroke, it is reasonable to choose CEA over CAS to reduce the periprocedural stroke rate. (Level of Evidence B-R)''

'' 7.        In patients with TIA or nondisabling stroke, when revascularization is indicated, it is reasonable to perform the procedure within 2 weeks of the index event rather than delay surgery to increase the likelihood of stroke-free outcome. (Level of Evidence C-LD)''

'' 8.       In patients with symptomatic severe stenosis (≥70%) in whom anatomic or medical condi-tions are present that increase the risk for surgery (such as radiation-induced stenosis or restenosis after CEA) it is reasonable to choose CAS to reduce the periprocedural complication rate. (Level of Evidence C-LD)''

Class IIb

" 9.        In symptomatic patients at average or low risk of complications associated with endovascular intervention, when the ICA stenosis is ≥70% by noninvasive imaging or >50% by catheter-based imaging and the anticipated rate of periprocedural stroke or death is <6%, CAS may be considered as an alternative to CEA for stroke prevention, particularly in patients with significant cardiovascular comorbidities predisposing to cardiovascular complications with endarterectomy (Level of Evidence A)".

'' 10.     In patients with a recent stroke or TIA (past 6 months), the usefulness of transcarotid artery revascularization (TCAR) for prevention of recurrent stroke and TIA is uncertain. (Level of Evidence B-NR)''

Class III (No Benefit)

"11. In patients with recent TIA or ischemic stroke and when the degree of stenosis is <50%, revascularization with CEA or CAS to reduce the risk of future stroke is not recommended.. (Level of Evidence:A) "

" 12. In patients with a recent (within 120 days) TIA or ischemic stroke ipsilateral to atherosclerotic stenosis or occlusion of the middle cerebral or carotid artery, extracranial intracranial bypass surgery is not recommended. (Level of Evidence B-NR)".

EXTRACRANIAL VERTEBRAL ARTERY STENOSIS

Class I

"1. In patients with recently symptomatic extra-cranial vertebral artery stenosis, intensive medical therapy (antiplatelet therapy, lipid lowering, BP control) is recommended to reduce stroke risk. (Level of evidence: A)"

Class IIb

" 2.   In patients with ischemic stroke or TIA and extracranial vertebral artery stenosis who are having symptoms despite optimal medical treatment, the usefulness of stenting is not well established. (Level of Evidence B-R)".

'' 3.   In patients with ischemic stroke or TIA and extracranial vertebral artery stenosis who are having symptoms despite optimal medical treatment, the usefulness of open surgical procedures, including vertebral endarterectomy and vertebral artery transposition, is not well established. (Level of Evidence C-EO)''

AORTIC ARCH ATHEROSCLEROSIS

Class I

"1. In patients with a stroke or TIA and evidence of an aortic arch atheroma, intensive lipid management to an LDL cholesterol target <70 mg/dL is recommended to prevent recur-rent stroke(Level of evidence: B-R)"

"2. In patients with a stroke or TIA and evidence of an aortic arch atheroma, antiplatelet therapy is recommended to prevent recurrent stroke..(Level of evidence: C-LD) "

2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association.

Moyamoya disease

Class IIa

" 1. In patients with moyamoya disease and a history of ischemic stroke or TIA, surgical revascularization with direct or indirect extracranial intracranial bypass can be beneficial for the prevention of ischemic stroke or TIA. (Level of Evidence C-LD)".

Class IIb

" 2. In patients with moyamoya disease and a history of ischemic stroke or TIA, the use of antiplatelet therapy, typically aspirin monotherapy, for the prevention of ischemic stroke or TIA may be reasonable. (Level of Evidence C-LD)".

Ischemic Stroke Caused by Small Vessel Disease

Class IIb

" 1.     In patients with ischemic stroke related to small vessel disease, the usefulness of cilostazol for secondary stroke prevention is uncertain. (Level of Evidence B-R)".

Cardioembolism: Atrial Fibrillation

Class I

"1.   In patients with nonvalvular AF and stroke or TIA, oral anticoagulation (eg, apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) is recommended to reduce the risk of recurrent stroke. (Level of evidence: A)"

"2.     In patients with AF and stroke or TIA, oral anticoagulation is indicated to reduce the risk of recurrent stroke regardless of whether the AF pattern is paroxysmal, persistent, or permanent. (Level of evidence: B-R) "

"3.  In patients with stroke or TIA and AF who do not have moderate to severe mitral stenosis or a mechanical heart valve, apixaban, dabigatran, edoxaban, or rivaroxaban is recommended in preference to warfarin to reduce the risk of recurrent stroke. (Level of evidence: B-R) "

"4.       In patients with atrial flutter and stroke or TIA, anticoagulant therapy similar to that in AF is indicated to reduce the risk of recurrent stroke. (Level of evidence: B-NR) "

"5.       In patients with AF and stroke or TIA, without moderate to severe mitral stenosis or a mechanical heart valve, who are unable to maintain a therapeutic INR level with warfarin, use of dabigatran, rivaroxaban, apixaban, or edoxaban is recommended to reduce the risk of recurrent stroke (Level of evidence: C-EO) "

Class IIa

" 6.     In patients with stroke at high risk of hemor-rhagic conversion in the setting of AF, it is reasonable to delay initiation of oral antico-agulation beyond 14 days to reduce the risk of ICH. (Level of Evidence B-NR)".

'' 7.   In patients with TIA in the setting of nonvalvular AF, it is reasonable to initiate anticoagulation immediately after the index event to reduce the risk of recurrent stroke. (Level of Evidence C-EO)''

Class IIb

" 8.       In patients with stroke or TIA in the setting of nonvalvular AF who have contraindications for lifelong anticoagulation but can tolerate at least 45 days, it may be reasonable to consider percutaneous closure of the left atrial appendage with the Watchman device to reduce the chance of recurrent stroke and bleeding. (Level of Evidence B-R)".

'' 9.      In patients with stroke at low risk for hemorrhagic conversion in the setting of AF, it may be reasonable to initiate anticoagulation 2 to 14 days after the index event to reduce the risk of recurrent stroke. (Level of Evidence B-NR)''

'' 10. In patients with AF and stroke or TIA who have end-stage renal disease or are on dialysis, it may be reasonable to use warfarin or apixaban (dose adjusted if indicated) for anticoagulation to reduce the chance of recurrent stroke. (Level of Evidence B-NR)''

Valvular disease

Class I

"1. In patients with ischemic stroke or TIA and valvular AF (moderate to severe mitral steno-sis or any mechanical heart valve), warfarin is recommended to reduce the risk of recurrent stroke or TIA. (Level of evidence: B-R)"

"2.     In patients with AF and stroke or TIA, oral anticoagulation is indicated to reduce the risk of recurrent stroke regardless of whether the AF pattern is paroxysmal, persistent, or permanent. (Level of evidence: C-LD) "

"3.      In patients with ischemic stroke or TIA and native aortic or nonrheumatic mitral valve disease (eg, mitral annular calcification or mitral valve prolapse) who do not have AF or another indication for anticoagulation, anti-platelet therapy is recommended to reduce the risk of recurrent stroke or TIA. (Level of evidence: C-EO) "

"4.       In patients with a bioprosthetic aortic or mitral valve, a history of ischemic stroke or TIA before valve replacement, and no other indication for anticoagulation therapy beyond 3 to 6 months from the valve placement, long-term therapy with aspirin is recommended in preference to long-term anticoagulation to reduce the risk of recur-rent stroke or TIA. (Level of evidence: C-EO) "

Class IIa

" 5.     In patients with ischemic stroke or TIA and IE who present with recurrent emboli and persistent vegetations despite appropriate antibiotic therapy, early surgery (during initial hospitalization before completion of a full therapeutic course of antibiotics) is reasonable to reduce the risk of recurrent embolism if there is no evidence of intracranial hemorrhage or extensive neurological damage. (Level of Evidence B-NR)".

'' 6.      In patients with history of ischemic stroke or TIA and a mechanical aortic valve, anti-coagulation with higher-intensity warfarin to achieve an INR of 3.0 (range, 2.5–3.5) or the addition of aspirin (75–100 mg/d) can be beneficial to reduce the risk of thromboem-bolic events. (Level of Evidence C-EO)''

Class IIb

" 7.   In patients with ischemic stroke or TIA and native left-sided valve endocarditis who exhibit mobile vegetations >10 mm in length, early surgery (during initial hospitalization before completion of a full therapeutic course of anti-biotics) may be considered to reduce the risk of recurrent embolism if there is no evidence of intracranial hemorrhage or extensive neurologi-cal damage. (Level of Evidence B-NR)".

''8.      In patients with ischemic stroke or TIA and IE, early valve surgery (during initial hospital-ization before completion of a full therapeutic course of antibiotics) may be considered in patients with an indication for surgery who have no evidence of intracranial hemorrhage or extensive neurological damage. (Level of Evidence B-NR)''

'' 9.     In patients with IE and major ischemic stroke, delaying valve surgery for at least 4 weeks may be considered for patients with IE and major ischemic stroke or intracranial hemorrhage if the patient is hemodynamically stable (Level of Evidence B-NR)''

Class III (Harm)

"10. In patients with ischemic stroke or TIA and mechanical heart valves, treatment with dabigatran causes harm. (Level of Evidence: B-R) "

Left Ventricular Thrombus

Class I

"1.     In patients with stroke or TIA and LV thrombus, anticoagulation with therapeutic warfarin for at least 3 months is recommended to reduce the risk of recurrent stroke. (Level of evidence: B-NR)"

Class IIa

" 2.     In patients with stroke or TIA in the setting of acute MI, it is reasonable to perform advanced cardiac imaging (eg, contrasted echocardiogram or cardiac MRI) to assess for the presence of LV thrombus. (Level of Evidence C-EO)".

Class IIb

" 3.       In patients with stroke or TIA and new LV thrombus (<3 months), the safety of anticoagulation with a direct oral anticoagulant to reduce the risk of recurrent stroke is uncertain. (Level of Evidence B-NR)".

''4.     In patients with stroke or TIA in the setting of acute anterior MI with reduced ejection fraction (EF; <50%) but no evidence of LV thrombus, empirical anticoagulation for at least 3 months might be considered to reduce the risk of recurrent cardioembolic stroke. (Level of Evidence B-NR)''

Cardiomyopathy

Class I

"1. In patients with ischemic stroke or TIA and left atrial or left atrial appendage thrombus in the setting of ischemic, nonischemic, or restrictive cardiomyopathy and LV dysfunction, anticoagulant therapy with warfarin is recommended for at least 3 months to reduce the risk of recurrent stroke or TIA (Level of evidence: C-EO)"

Class IIa

" 2.   In patients with ischemic stroke or TIA in the setting of a mechanical assist device, treatment with warfarin and aspirin can be beneficial to reduce the risk of recurrent stroke or TIA. (Level of Evidence C-LD)".

''3.      In patients with ischemic stroke or TIA in the setting of LV noncompaction, treatment with warfarin can be beneficial to reduce the risk of recurrent stroke or TIA. (Level of Evidence C-EO)''

Class IIb

" 4.  In patients with ischemic stroke or TIA in sinus rhythm with ischemic or nonischemic cardio-myopathy and reduced EF without evidence of left atrial or LV thrombus, the effectiveness of anticoagulation compared with antiplatelet therapy is uncertain, and the choice should be individualized. (Level of Evidence B-R)".

Class III (Harm)

"5. In patients with stroke or TIA and LV assist devices (LVADs), treatment with dabigatran instead of warfarin for the primary or secondary prevention of ischemic stroke or TIA causes harm. (Level of Evidence: B-R) "

Patent Foramen Ovale

Class I

"1.     In patients with a non-lacunar ischemic stroke of undetermined cause and a PFO, recommendations for PFO closure versus medical management should be made jointly by the patient, a cardiologist, and a neurologist, taking into account the probability of a causal role for the PFO. (Level of evidence: C-EO)"

Class IIa

" 2.    In patients 18 to 60 years of age with a non-lacunar ischemic stroke of undetermined cause despite a thorough evaluation and a PFO with high-risk anatomic features, it is reasonable to choose closure with a transcatheter device and long-term antiplatelet therapy over antiplatelet therapy alone for preventing recurrent stroke. (Level of Evidence B-R)".

Class IIb

" 3.   In patients 18 to 60 years of age with a nonlacunar ischemic stroke of undetermined cause despite a thorough evaluation and a PFO without high risk anatomic features, the benefit of closure with a transcatheter device and long-term antiplatelet therapy over antiplatelet therapy alone for preventing recurrent stroke is not well established. (Level of Evidence C-LD)".

''4.      In patients 18 to 60 years of age with a nonlacunar ischemic stroke of undetermined cause despite a thorough evaluation and a PFO, the comparative benefit of closure with a transcatheter device versus warfarin is unknow. (Level of Evidence C-LD)''

Congenital Heart Disease

Class I

"1.     In patients with ischemic stroke or TIA and Fontan palliation, anticoagulation with warfarin is recommended to reduce the risk of recur-rent stroke or TIA. (Level of evidence: C-LD)"

Class IIa

" 2. In patients with cyanotic congenital heart disease and other complex lesions, ischemic stroke, or TIA of presumed cardioembolic origin, therapy with warfarin is reasonable to reduce the risk of recurrent stroke or TIA. (Level of Evidence: C-EO)".

Cardiac Tumors

Class IIa

" 1.     In patients with stroke or TIA found to have a left sided cardiac tumor, resection of the tumor can be beneficial to reduce the risk of recurrent stroke. (Level of Evidence: C-LD)".

Dissection

Class I

"1.    In patients with ischemic stroke or TIA after an extracranial carotid or vertebral arterial dissection, treatment with antithrombotic therapy for at least 3 months is indicated to prevent recurrent stroke or TIA. (Level of evidence: C-EO)"

Class IIa

" 2. In patients with ischemic stroke or TIA who are <3 months after an extracranial carotid or vertebral arterial dissection, it is reasonable to use either aspirin or warfarin to prevent recurrent stroke or TIA. (Level of Evidence: B-R)".

Class IIb

" 3.    In patients with stroke or TIA and extracranial carotid or vertebral artery dissection who have recurrent events despite antithrombotic therapy, endovascular therapy may be considered to prevent recurrent stroke or TIA.. (Level of Evidence: C-LD)".

Hypercoagulable States. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association.

Hematologic Traits

Class IIa

" 1.  In patients with ischemic stroke or TIA of unknown source despite thorough diagnostic evaluation and no other thrombotic history who are found to have prothrombin 20210A mutation, activated protein C resistance, elevated factor VIII levels, or deficiencies of protein C, protein S, or antithrombin III, anti-platelet therapy is reasonable to reduce the risk of recurrent stroke or TIA.. (Level of Evidence: C-LD)".

Antiphospholipid Syndrome

Class I

"1.     In patients with ischemic stroke or TIA who have an isolated antiphospholipid antibody but do not fulfill the criteria for antiphospholipid syndrome, antiplatelet therapy alone is recommended to reduce the risk of recurrent stroke (Level of evidence: B-NR)"

Class IIa

" 2.     In patients with ischemic stroke or TIA with confirmed antiphospholipid syndrome treated with warfarin, it is reasonable to choose a target INR between 2 and 3 over a target INR >3 to effectively balance the risk of excessive bleeding against the risk of thrombosis. (Level of Evidence B-R)".

''3.  In patients with ischemic stroke or TIA who meet the criteria for the antiphospholipid syndrome, it is reasonable to anticoagulate with warfarin to reduce the risk of recurrent stroke or TIA. (Level of Evidence C-LD)''

Class III (Harm)

"4. In patients with ischemic stroke or TIA, antiphospholipid syndrome with a history of thrombosis and triple-positive antiphospholipid antibodies (ie, lupus anticoagulant, anticardiolipin, and anti– β2 glycoprotein-I), rivaroxaban is not recommended because it is associated with excess thrombotic events compared with warfarin (Level of Evidence: B-R) "

Hyperhomocysteinemia

Class III (No Benefit)

"1. In patients with ischemic stroke or TIA with hyperhomocysteinemia, supplementation with folate, vitamin B6, and vitamin B12 is not effective for preventing subsequent stroke. (Level of Evidence: B-R) "

Malignancy

Class IIa

" 1.   In patients with ischemic stroke or TIA in the setting of AF and cancer, it is reasonable to consider anticoagulation with DOACs in preference to warfarin for stroke prevention (Level of Evidence B-NR)".

Sickle Cell Disease

Class I

"1.   In patients with sickle cell disease (SCD) and prior ischemic stroke or TIA, chronic blood transfusion(s) to reduce hemoglobin S to <30% of total hemoglobin is recommended for the prevention of recurrent ischemic stroke.(Level of evidence: B-NR)"

Class IIa

" 2.  In patients with SCD with prior ischemic stroke or TIA for whom transfusion therapy is not available or practical, treatment with hydroxyurea is reasonable for the prevention of recurrent ischemic stroke. (Level of Evidence B-R)".

Autoinmune Vasculitis

Class I

"1.     In patients with ischemic stroke or TIA and symptoms attributed to giant cell arteritis, immediate initiation of oral high-dose glucocorticoids is recommended to reduce recurrent stroke risk..(Level of evidence: B-NR)"

Class IIa

" 2. .     In patients with ischemic stroke or TIA and diagnosis of giant cell arteritis, methotrexate or tocilizumab therapy adjunctive to steroids is reasonable to lower the risk of recurrent stroke. (Level of Evidence B-NR)".

''3.      In patients with ischemic stroke or TIA and diagnosis of primary CNS angiitis, induction therapy with glucocorticoids and/or immunosuppressants followed by long-term maintenance therapy with steroid-sparing immunosuppressants is reasonable to lower the risk of stroke recurrence. (Level of Evidence C-LD)''

Class III (Harm)

"4.     In patients with ischemic stroke or TIA and confirmed diagnosis of giant cell arteritis, infliximab is associated with recurrent ocular symptoms and markers of disease activity and should not be administered. (Level of Evidence: B-R) "

Infectious Vasculitis

Class I

"1. In patients with ischemic stroke or TIA and infectious vasculitides such as a varicella-zoster virus (VZV) cerebral vasculitis, neurosyphilis, or bacterial meningitis, treating the underlying infectious etiology is indicated to reduce the risk of stroke.7(Level of evidence: B-NR)"

Class IIa

" 2.     In patients with ischemic stroke or TIA in the context of HIV vasculopathy, daily aspirin plus HIV viral control with combined antiretroviral therapy is reasonable to reduce the risk of recurrent stroke (Level of Evidence C-LD)".

Other Genetic disorders

Class I

"1. In patients with ischemic stroke or TIA and cystathionine β-synthase deficiency, pyridoxine (in responsive patients) and a low-methionine, a cysteine-enhanced diet supplemented with pyridoxine, vitamin B12, and folate are recommended to reduce plasma homocysteine to population normal levels and thereby reduce the risk of recurrent ischemic stroke.(Level of evidence: C-LD)"

Class IIb

" 2. In patients with ischemic stroke or TIA and Anderson-Fabry disease, agalsidase alfa or agalsidase beta is of uncertain value in preventing recurrent stroke or TIA. (Level of Evidence B-NR)".

Carotid Web

Class I

"1. In patients with a carotid web in the distribution of ischemic stroke and TIA, without other attributable causes of stroke, antiplatelet therapy is recommended to prevent recurrent ischemic stroke or TIA. (Level of evidence: B-NR)"

Class IIb

" 2.     In patients with the carotid web in the distribution of ischemic stroke refractory to medical management, with no other attributable cause of stroke despite comprehensive workup, carotid stenting or CEA may be considered to prevent recurrent ischemic stroke. (Level of Evidence C-LD)".

Fibromuscular Dysplasia

Class I

"1. In patients with fibromuscular dysplasia (FMD) and a history of ischemic stroke or TIA without other attributable causes, antiplatelet therapy, BP control, and lifestyle modification are recommended for the prevention of future ischemic events (Level of evidence: C-LD)"

Class IIa

" 2. In patients with a history of ischemic stroke or TIA attributable to dissection, with FMD, and no evidence of intraluminal thrombus, it is reasonable to administer antiplatelet therapy for the prevention of future ischemic events. (Level of Evidence C-EO)".

Class IIb

" 3.  In patients with cervical carotid artery FMD and recurrent ischemic stroke without other attributable causes despite optimal medical management, carotid angioplasty with or without stenting may be reasonable to prevent ischemic stroke. (Level of Evidence C-LD)".

Dolichoectasia

Class IIa

" 1.     In patients with vertebrobasilar dolichoectasia and a history of ischemic stroke or TIA without other attributable causes, the use of antiplatelet or anticoagulant therapy is reasonable for the prevention of recurrent ischemic events. (Level of Evidence C-LD)".

Embolic Stroke of Undetermined Source

Class III (No Benefit)

".1     In patients with ESUS, treatment with direct oral anticoagulants is not recommended to reduce risk of secondary stroke. (Level of Evidence: B-R) "

" 2.     In patients with ESUS, treatment with ticagrelor is not recommended to reduce the risk of secondary stroke (Level of Evidence B-NR)".

Antithrombotic Medications in Secondary Stroke Prevention. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association.

Class I

"1. In patients with noncardioembolic ischemic stroke or TIA, antiplatelet therapy is indicated in preference to oral anticoagulation to reduce the risk of recurrent ischemic stroke and other cardiovascular events while minimizing the risk of bleeding. (Level of evidence: A)"

"2. For patients with noncardioembolic ischemic stroke or TIA, aspirin 50 to 325 mg daily, clopidogrel 75 mg, or the combination of aspi-rin 25 mg and extended-release dipyridamole 200 mg twice daily is indicated for secondary prevention of ischemic stroke. (Level of evidence: A) "

"  3. For patients with recent minor (NIHSS score ≤3) noncardioembolic ischemic stroke or high-risk TIA (ABCD2 score ≥4), DAPT (aspirin plus clopidogrel) 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 SAPT, to reduce the risk of recurrent ischemic stroke. (Level of evidence: A) "

Class IIb

" 4. For patients with recent (< 24 hours) minor to moderate stroke (NIHSS score ≤5), high-risk TIA (ABCD2 score ≥6), or symptomatic intracranial or extracranial ≥30% stenosis of an artery that could account for the event, DAPT with ticagrelor plus aspirin for 30 days may be considered to reduce the risk of 30-day recur-rent stroke but may also increase the risk of serious bleeding events, including ICH. (Level of Evidence B-NR)".

''5. For patients already taking aspirin at the time of non-cardioembolic ischemic stroke or TIA, the effectiveness of increasing the dose of aspirin or changing to another antiplatelet medication is not well established. (Level of Evidence C-LD)''

Class III (Harm)

".6. For patients with non-cardioembolic ischemic stroke or TIA, the continuous use of DAPT (aspirin plus clopidogrel) for >90 days or the use of triple antiplatelet therapy is associated with excess risk of hemorrhage. (Level of Evidence: A) "

Secondary Prevention. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association.

Health Systems–Based Interventions for Secondary Stroke Prevention

Class I

"1. In patients with ischemic stroke or TIA, voluntary hospital-based or outpatient-focused quality monitoring and improvement programs are recommended to improve short-term and long-term adherence to nationally accepted, evidence-based guidelines for secondary stroke prevention. (Level of evidence: C-EO)"

Class IIa

"2. In patients with ischemic stroke or TIA, a multidisciplinary outpatient team-based approach (ie, care provision with active medication adjustment from advanced practice providers, nurses, or pharmacists) can be effective to control BP, lipids, and other vascular risk factors. (Level of Evidence B-R)".

''3. In patients presenting to their primary care provider as the first contact after TIA or minor stroke, it is reasonable to use a decision sup-port tool that improves diagnostic accuracy, stratifies patients in risk categories to support appropriate triage, and prompts the initiation of medications and counseling for lifestyle modification for secondary stroke prevention to reduce the 90-day risk of recurrent stroke or TIA. (Level of Evidence B-R)''

Interventions Aimed at Changing Patient Behavior

Class I

"1. In patients with ischemic stroke or TIA, behavior change interventions targeting stroke literacy, lifestyle factors, and medication adherence are recommended to reduce cardiovascular events. (Level of evidence: B-R)"

Class IIa

"2. In patients with ischemic stroke or TIA, teaching self-management skills or using behavior change theory (eg, motivational interviewing) can be beneficial in improving medication adherence (Level of Evidence B-R)".

''3. In patients with stroke or TIA, combined exercise-based and behavior change interventions are probably indicated in preference to behavior interventions alone, exercise interventions alone, or usual care to reduce physiological stroke risk factors such as SBP (Level of Evidence B-R)''

'' 4. In patients with TIA or nondisabling stroke, engagement in targeted secondary prevention programs (eg, cardiac rehabilitation programs or exercise and lifestyle counseling programs) can be beneficial to reduce risk factors and recurrent ischemic events. (Level of Evidence B-R)''

''5. For patients with disabling stroke who are discharged from acute services, engaging in targeted secondary prevention programs (eg, an adapted cardiac rehabilitation program or structured exercise including aerobic activity and healthy lifestyle counseling) can be beneficial to reduce vascular risk factors and mortality. (Level of Evidence B-NR)''

Class III (No Benefit)

"6. In patients with stroke or TIA, provision of health information or advice about stroke prevention is essential; however, information or advice alone, in the absence of a behavioral intervention, is not an effective means to change modifiable, lifestyle-related risk factors in order to reduce future ischemic events (Level of Evidence: B-R) "

Health Equity

Class I

"1. In patients with stroke or TIA, evaluating and addressing social determinants of health (eg, literacy level, language proficiency, medication affordability, food insecurity, housing, and transportation barriers) when managing stroke risk factors is recommended to reduce healthcare disparities. (Level of evidence: C-EO)"

"2. In patients with stroke or TIA, monitoring the achievement of nationally accepted, evidence-based performance measures is recommended to allow inequities to be identified and addressed. (Level of evidence: C-EO) "

"3. In patients with stroke or TIA, systematic adoption of the Agency for Healthcare Research and Quality Universal Precautions Toolkit for Health Literacy is recommended to integrate health literacy into the secondary prevention of stroke. (Level of evidence: C-EO) "

Class IIb

"4. In patients from urban, predominantly minority, or low-socioeconomic-status groups with stroke or TIA, the optimal intervention model for improving stroke risk factor control and reducing disparities is unknown. (Level of Evidence B-R)".