AHA/ASA guideline recommendations for secondary prevention of stroke

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]

2014 AHA/ASA Guidelines for the Secondary Prevention of Stroke

Hypertension

Class I

"1. Initiation of BP therapy is indicated for previously untreated patients with ischemic stroke or TIA who, after the first several days, have an established BP ≥140 mm Hg systolic or ≥90 mm Hg diastolic.  (Level of Evidence: B)"

"2. Resumption of BP therapy is indicated for previously treated patients with known hypertension for both prevention of recurrent stroke and prevention of other vascular events in those who have had an ischemic stroke or TIA and are beyond the first several days (Level of Evidence: A)"

"3. The optimal drug regimen to achieve the recommended level of reductions is uncertain because direct comparisons between regimens are limited. The available data indicate that diuretics or the combination of diuretics and an angiotensin-converting enzyme inhibitor is useful. (Level of Evidence: A)"

Class IIb

"1. Goals for target BP level or reduction from pretreatment baseline are uncertain and should be individualized, but it is reasonable to achieve a systolic pressure <140 mm Hg and a diastolic pressure <90 mm Hg. (Level of Evidence: B)"

"2. Several lifestyle modifications have been associated with BP reductions and are a reasonable part of a comprehensive antihypertensive therapy.(Level of Evidence: C)"

"3. The choice of specific drugs and targets should be individualized on the basis of pharmacological properties, mechanism of action, and consideration of specific patient characteristics for which specific agents are probably indicated (eg, extracranial cerebrovascular occlusive disease, renal impairment, cardiac disease, and DM). (Level of Evidence: B)"

Class IIb

"1. Initiation of therapy for patients with BP <140 mm Hg systolic and <90 mm Hg diastolic is of uncertain benefit (Level of Evidence: C)"

"2. For patients with a recent lacunar stroke, it might be reasonable to target an SBP of <130 mm Hg (Level of Evidence: B)"

Dyslipidemia

Class I

"1. Statin therapy with intensive lipid-lowering effects is recommended to reduce risk of stroke and cardiovascular events among patients with ischemic stroke or TIA presumed to be of atherosclerotic origin and an LDL-C level ≥100 mg/dL with or without evidence for other clinical ASCVD. (Level of Evidence: B)"

"2. Statin therapy with intensive lipid-lowering effects is recommended to reduce risk of stroke and cardiovascular events among patients with ischemic stroke or TIA presumed to be of atherosclerotic origin, an LDL-C level <100 mg/dL, and no evidence for other clinical ASCVD. (Level of Evidence: C)"

"3. Patients with ischemic stroke or TIA and other comorbid ASCVD should be otherwise managed according to the 2013 ACC/AHA cholesterol guidelines,16 which include lifestyle modification, dietary recommendations, and medication recommendations. (Level of Evidence: A)"

Disorders of Glucose Metabolism and DM

Class I

"1. Use of existing guidelines from the ADA for glycemic control and cardiovascular risk factor management is recommended for patients with an ischemic stroke or TIA who also have DM or pre-DM. (Level of Evidence: B)"

Class IIa

"1. After a TIA or ischemic stroke, all patients should probably be screened for DM with testing of fasting plasma glucose, HbA1c, or an oral glucose tolerance test. Choice of test and timing should be guided by clinical judgment and recognition that acute illness may temporarily perturb measures of plasma glucose. In general, HbA1c may be more accurate than other screening tests in the immediate postevent period. (Level of Evidence: C)"

Class I

"1. All patients with TIA or stroke should be screened for obesity with measurement of BMI . (Level of Evidence: C)"

Class IIb

"1. Despite the demonstrated beneficial effects of weight loss on cardiovascular risk factors, the usefulness of weight loss among patients with a recent TIA or ischemic stroke and obesity is uncertain. (Level of Evidence: C)"

Metabolic Syndrome

Class I

"1. Preventive care for patient with the metabolic syndrome should include appropriate treatment for individual components of the syndrome, which are also stroke risk factors, particularly dyslipidemia and hypertension. (Level of Evidence: A)"

"2. For patients who are screened and classified as having the metabolic syndrome, management should focus on counseling for lifestyle modification (diet, exercise, and weight loss) for vascular risk reduction. (Level of Evidence: C)"</nowiki |- |} {|class="wikitable" |- | colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]] |- |bgcolor="LemonChiffon"|<nowiki>"1. At this time, the usefulness of screening patients for the metabolic syndrome after stroke is unknown. (Level of Evidence: C)"

Physical Inactivity

Class IIa

"1. For patients with ischemic stroke or TIA who are capable of engaging in physical activity, at least 3 to 4 sessions per week of moderate- to vigorous-intensity aerobic physical exercise are reasonable to reduce stroke risk factors. Sessions should last an average of 40 minutes. Moderate-intensity exercise is typically defined as sufficient to break a sweat or noticeably raise heart rate (eg, walking briskly, using an exercise bicycle). Vigorous-intensity exercise includes activities such as jogging. (Level of Evidence: C)"

"2. For patients who are able and willing to initiate increased physical activity, referral to a comprehensive, behaviorally oriented program is reasonable At this time, the usefulness of screening patients for the metabolic syndrome after stroke is unknown. (Level of Evidence: C)"

Class IIb

"1. For individuals with disability after ischemic stroke, supervision by a healthcare professional such as a physical therapist or cardiac rehabilitation professional, at least on initiation of an exercise regimen, may be considered . (Level of Evidence: C)"

Nutrition

Class I

"1. Patients with a history of ischemic stroke or TIA and signs of undernutrition should be referred for individualized nutritional counseling. (Level of Evidence: B)"

Class IIa

"1. It is reasonable to conduct a nutritional assessment for patients with a history of ischemic stroke or TIA, looking for signs of overnutrition or undernutrition. (Level of Evidence: C)"

"2. It is reasonable to recommend that patients with a history of stroke or TIA reduce their sodium intake to less than ≈2.4 g/d. Further reduction to <1.5 g/d is also reasonable and is associated with even greater BP reduction. (Level of Evidence: C)"

"3. It is reasonable to counsel patients with a history of stroke or TIA to follow a Mediterranean-type diet instead of a low-fat diet. The Mediterranean-type diet emphasizes vegetables, fruits, and whole grains and includes low-fat dairy products, poultry, fish, legumes, olive oil, and nuts. It limits intake of sweets and red meats. (Level of Evidence: C)"

Class III (Harm)

"1. Routine supplementation with a single vitamin or combination of vitamins is not recommended. (Level of Evidence: A)"

Obstructive Sleep Apnea

Class IIb

"1. A sleep study might be considered for patients with an ischemic stroke or TIA on the basis of the very high prevalence of sleep apnea in this population and the strength of the evidence that the treatment of sleep apnea improves outcomes in the general population. (Level of Evidence: B)"

"2. Treatment with CPAP might be considered for patients with ischemic stroke or TIA and sleep apnea given the emerging evidence in support of improved outcomes. (Level of Evidence: B)"

Cigarette Smoking

Class I

"1. Healthcare providers should strongly advise every patient with stroke or TIA who has smoked in the past year to quit. (Level of Evidence: C)"

"2. Counseling, nicotine products, and oral smoking cessation medications are effective in helping smokers to quit . (Level of Evidence: A)"

Class IIa

"1. It is reasonable to advise patients after TIA or ischemic stroke to avoid environmental (passive) tobacco smoke. (Level of Evidence: B)"

Alcohol Consumption

Class I

"1. Patients with ischemic stroke, TIA, or hemorrhagic stroke who are heavy drinkers should eliminate or reduce their consumption of alcohol. (Level of Evidence: C)"

Class IIb

"1. Light to moderate amounts of alcohol consumption (up to 2 drinks per day for men and up to 1 drink per day for nonpregnant women) may be reasonable, although nondrinkers should not be counseled to start drinking. (Level of Evidence: B)"

Interventional Approaches for the Patient With Large-Artery Atherosclerosis

Extracranial Carotid Disease

Class I

"1. For patients with a TIA or ischemic stroke within the past 6 months and ipsilateral severe (70%–99%) carotid artery stenosis as documented by noninvasive imaging, CEA is recommended if the perioperative morbidity and mortality risk is estimated to be <6%. (Level of Evidence: A)"

"2. For patients with recent TIA or ischemic stroke and ipsilateral moderate (50%–69%) carotid stenosis as documented by catheter-based imaging or noninvasive imaging with corroboration (eg, magnetic resonance angiogram or computed tomography angiogram), CEA is recommended 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)"

"3. CAS and CEA in the above settings should be performed by operators with established periprocedural stroke and mortality rates of <6% for symptomatic patients, similar to that observed in trials comparing CEA to medical therapy and more recent observational studies. (Level of Evidence: B)"

"4. Optimal medical therapy, which should include antiplatelet therapy, statin therapy, and risk factor modification, is recommended for all patients with carotid artery stenosis and a TIA or stroke, as outlined elsewhere in this guideline. (Level of Evidence: A)"

Class IIa

"1. When revascularization is indicated for patients with TIA or minor, nondisabling stroke, it is reasonable to perform the procedure within 2 weeks of the index event rather than delay surgery if there are nocontraindications to early revascularization. (Level of Evidence: B)"

"2. CAS is indicated as an alternative to CEA for symptomatic patients at average or low risk of complications associated with endovascular intervention when the diameter of the lumen of the ICA is reduced by >70% by noninvasive imaging or >50% by catheter-based imaging or noninvasive imaging with corroboration and the anticipated rate of periprocedural stroke or death is <6%. (Level of Evidence: B)"

"3. It is reasonable to consider patient age in choosing between CAS and CEA. For older patients (ie, older than ≈70 years), CEA may be associated with improved outcome compared with CAS, particularly when arterial anatomy is unfavorable for endovascular intervention. For younger patients, CAS is equivalent to CEA in terms of risk for periprocedural complications (ie, stroke, MI, or death) and long-term risk for ipsilateral stroke. (Level of Evidence: B)"

"4. Among patients with symptomatic severe stenosis (>70%) in whom anatomic or medical conditions are present that greatly increase the risk for surgery or when other specific circumstances exist such as radiation-induced stenosis or restenosis after CEA, CAS is reasonable. (Level of Evidence: B)"

Class IIb

"1. For patients with recurrent or progressive ischemic symptoms ipsilateral to a stenosis or occlusion of a distal (surgically inaccessible) carotid artery, or occlusion of a midcervical carotid artery after institution of optimal medical therapy, the usefulness of EC/IC bypass is considered investigational. (Level of Evidence: C)"

Class III (Harm)

"1. When the degree of stenosis is <50%, CEA and CAS are not recommended ( (Level of Evidence: A)"

"2. Routine, long-term follow-up imaging of the extracranial carotid circulation with carotid duplex ultrasonography is not recommended (Level of Evidence: B)"

"3. For patients with a recent (within 6 months) TIA or ischemic stroke ipsilateral to a stenosis or occlusion of the middle cerebral or carotid artery, EC/ IC bypass surgery is not recommended (Level of Evidence: A)"

Extracranial Vertebrobasilar Disease

Class I

"1. Routine preventive therapy with emphasis on antithrombotic therapy, lipid lowering, BP control, and lifestyle optimization is recommended for all patients with recently symptomatic extracranial vertebral artery stenosis. (Level of Evidence: C)"

Class IIb

"1. Endovascular stenting of patients with extracranial vertebral stenosis may be considered when patients are having symptoms despite optimal medical treatment. (Level of Evidence: C)"

"2. Open surgical procedures, including vertebral endarterectomy and vertebral artery transposition, may be considered when patients are having symptoms despite optimal medical treatment (Level of Evidence: C)

Intracranial Atherosclerosis

Class I

"1. For 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. (Level of Evidence: B)"

"2. For patients with a stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery, maintenance of SBP below 140 mm Hg and high intensity statin therapy are recommended. (Level of Evidence: B)"

Class IIb

"1. For 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 90 days might be reasonable. (Level of Evidence: B)"

"2. For patients with stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery, the data are insufficient to make a recommendation regarding the usefulness of clopidogrel alone, the combination of aspirin and dipyridamole, or cilostazol alone. (Level of Evidence: C)"

"3. For patients with stroke or TIA attributable to severe stenosis (70%–99%) of a major intracranial artery, the usefulness of angioplasty alone or placement of stents other than the Wingspan stent is unknown and is considered investigational. (Level of Evidence: C)"

"4. For patients with severe stenosis (70%–99%) of a major intracranial artery and recurrent TIA or stroke after institution of aspirin and clopidogrel therapy, achievement of SBP <140 mm Hg, and high- intensity statin therapy, the usefulness of angioplasty alone or placement of a Wingspan stent or other stent is unknown and is considered investigational. (Level of Evidence: C)"

"5. For patients with severe stenosis (70%–99%) of a major intracranial artery and actively progressing symptoms after institution of aspirin and clopidogrel therapy, the usefulness of angioplasty alone or placement of a Wingspan stent or other stents is unknown and is considered investigational. (Level of Evidence: C)"

Class III (Harm)

"1. For patients with a stroke or TIA attributable to moderate stenosis (50%–69%) of a major intracranial artery, angioplasty or stenting is not recommended given the low rate of stroke with medical management and the inherent periprocedural risk of endovascular treatment. (Level of Evidence: B)"

"2. For patients with stroke or TIA attributable to severe stenosis (70%–99%) of a major intracranial artery, stenting with the Wingspan stent system is not recommended as an initial treatment, even for patients who were taking an antithrombotic agent at the time of the stroke or TIA. (Level of Evidence: B)"

"3. For patients with stroke or TIA attributable to 50% to 99% stenosis of a major intracranial artery, EC/IC bypass surgery is not recommended. (Level of Evidence: B)"

Medical Treatments for Patients With Cardiogenic Embolism

Atrial Fibrillation

Class I

"1. VKA therapy (Class I; Level of Evidence A), apixaban(Class I; Level of Evidence A), and dabigatran (Class I; Level of Evidence B) are all indicated for the prevention of recurrent stroke in patients with nonvalvular AF, whether paroxysmal or permanent. The selection of an antithrombotic agent should be individualized on the basis of risk factors, cost, tolerability, patient preference, potential for drug interactions, and other clinical characteristics, including renal function and time in INR therapeutic range if the patient has been taking VKA therapy. (Level of Evidence: A)"

"2. For patients with ischemic stroke or TIA with paroxysmal (intermittent), persistent, or permanent AF in whom VKA therapy is begun, a target INR of 2.5 is recommended (range, 2.0–3.0). (Level of Evidence: A)"

"3. For patients with ischemic stroke or TIA and AF who are unable to take oral anticoagulants, aspirin alone is recommended. (Level of Evidence: A)"

Class IIa

"1. For patients who have experienced an acute ischemic stroke or TIA with no other apparent cause, prolonged rhythm monitoring (≈30 days) for AF is reasonable within 6 months of the index event. (Level of Evidence: C)"

"2. Rivaroxaban is reasonable for the prevention of recurrent stroke in patients with nonvalvular AF. (Level of Evidence: B)"

"3. For most patients with a stroke or TIA in the setting of AF, it is reasonable to initiate oral anticoagulation within 14 days after the onset of neurological symptoms. (Level of Evidence: B)"

"4. In the presence of high risk for hemorrhagic conversion (ie, large infarct, hemorrhagic transformation on initial imaging, uncontrolled hypertension, or hemorrhage tendency), it is reasonable to delay initiation of oral anticoagulation beyond 14 days. (Level of Evidence: B)"

"5. For patients with AF and a history of stroke or TIA who require temporary interruption of oral anticoagulation, bridging therapy with an LMWH (or equivalent anticoagulant agent if intolerant to heparin) is reasonable, depending on perceived risk for thromboembolism and bleeding. (Level of Evidence: C)"

Class IIb

"1. The combination of oral anticoagulation (ie, warfarin or one of the newer agents) with antiplatelet therapy is not recommended for all patients after ischemic stroke or TIA but is reasonable in patients with clinically apparent CAD, particularly an acute coronary syndrome or stent placement. (Level of Evidence: C)"

"2. The addition of clopidogrel to aspirin therapy, compared with aspirin therapy alone, might be reasonable. (Level of Evidence: B)"

"3. The usefulness of closure of the left atrial appendage with the WATCHMAN device in patients with ischemic stroke or TIA and AF is uncertain. (Level of Evidence: B)"

Acute MI and LV Thrombus

Class I

"1. Treatment with VKA therapy (target INR, 2.5; range, 2.0–3.0) for 3 months is recommended in most patients with ischemic stroke or TIA in the setting of acute MI complicated by LV mural thrombus formation identified by echocardiography or another imaging modality (Class I; Level of Evidence C). Additional antiplatelet therapy for cardiac protection may be guided by recommendations such as those from the ACCP. (Level of Evidence: C)"

Class IIb

"1. Treatment with VKA therapy (target INR, 2.5; range, 2.0–3.0) for 3 months may be considered in patients with ischemic stroke or TIA in the setting of acute anterior STEMI without demonstrable LV mural thrombus formation but with anterior apical akinesis or dyskinesis identified by echocardiography or other imaging modality. (Level of Evidence: C)"

"2. In patients with ischemic stroke or TIA in the setting of acute MI complicated by LV mural thrombus formation or anterior or apical wall-motion abnormalities with an LV ejection fraction <40% who are intolerant to VKA therapy because of nonhemorrhagic adverse events, treatment with an LMWH, dabigatran, rivaroxaban, or apixaban for 3 months may be considered as an alternative to VKA therapy for prevention of recurrent stroke or TIA. (Level of Evidence: C)"

Cardiomyopathy

Class I

"1. In patients with ischemic stroke or TIA in sinus rhythm who have left atrial or LV thrombus demonstrated by echocardiography or another imaging modality, anticoagulant therapy with a VKA is recommended for ≥3 month. (Level of Evidence: C)"

Class IIa

"1. In patients with ischemic stroke or TIA in the setting of a mechanical LVAD, treatment with VKA therapy (target INR, 2.5; range, 2.0–3.0) is reasonable in the absence of major contraindications (eg, active gastrointestinal bleeding). (Level of Evidence: C)"

Class IIb

"1. In patients with ischemic stroke or TIA in sinus rhythm with either dilated cardiomyopathy (LV ejection fraction ≤35%) or restrictive cardiomyopathy 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: C)"

"2. In patients with ischemic stroke or TIA in sinus rhythm with dilated cardiomyopathy (LV ejection fraction ≤35%), restrictive cardiomyopathy, or a mechanical LVAD who are intolerant to VKA therapy because of nonhemorrhagic adverse events, the effectiveness of treatment with dabigatran, rivaroxaban, or apixaban is uncertain compared with VKA therapy for prevention of recurrent stroke. (Level of Evidence: C)"

Mitral Stenosis, Mitral Regurgitation, Mitral Prolapse, Mitral Annular Calcification, and Aortic Valve Disease

Class I

"1. For patients with ischemic stroke or TIA who have rheumatic mitral valve disease and AF, long-term VKA therapy with an INR target of 2.5 (range, 2.0– 3.0) is recommended. (Level of Evidence: A)"

"2. For patients with ischemic stroke or TIA and native aortic or nonrheumatic mitral valve disease who do not have AF or another indication for anticoagulation, antiplatelet therapy is recommended. (Level of Evidence: C)"

"3. For patients with ischemic stroke or TIA and mitral annular calcification who do not have AF or another indication for anticoagulation, antiplatelet therapy is recommended as it would be without the mitral annular calcification. (Level of Evidence: C)"

"4. For patients with mitral valve prolapse who have ischemic stroke or TIAs and who do not have AF or another indication for anticoagulation, antiplatelet therapy is recommended as it would be without mitral valve prolapse. (Level of Evidence: C)"

Class IIb

"1. For patients with ischemic stroke or TIA who have rheumatic mitral valve disease without AF or another likely cause for their symptoms (eg, carotid stenosis), long-term VKA therapy with an INR target of 2.5 (range, 2.0–3.0) may be considered instead of antiplatelet therapy. (Level of Evidence: C)"

"2. For patients with rheumatic mitral valve disease who have an ischemic stroke or TIA while being treated with adequate VKA therapy, the addition of aspirin might be considered. (Level of Evidence: C)"

Class III (Harm)

"1. For patients with rheumatic mitral valve disease who are prescribed VKA therapy after an ischemic stroke or TIA, antiplatelet therapy should not be routinely added. (Level of Evidence: C)"

Prosthetic Heart Valve

Class I

"1. For patients with a mechanical aortic valve and a history of ischemic stroke or TIA before its insertion, VKA therapy is recommended with an INR target of 2.5 (range, 2.0–3.0). (Level of Evidence: B)"

"2. For patients with a mechanical mitral valve and a history of ischemic stroke or TIA before its insertion, VKA therapy is recommended with an INR target of 3.0 (range, 2.5–3.5). (Level of Evidence: C)"

"3. For patients with a mechanical mitral or aortic valve who have a history of ischemic stroke or TIA before its insertion and who are at low risk for bleeding, the addition of aspirin 75 to 100 mg/d to VKA therapy is recommended. (Level of Evidence: B)"

"4. For patients with a bioprosthetic aortic or mitral valve, a history of ischemic stroke or TIA before its insertion, and no other indication for anticoagulation therapy beyond 3 to 6 months from the valve placement, long-term therapy with aspirin 75 to 100 mg/d is recommended in preference to long-term anticoagulation. (Level of Evidence: C)"

Class IIa

"1. For patients with a mechanical heart valve who have an ischemic stroke or systemic embolism despite adequate antithrombotic therapy, it is reasonable to intensify therapy by increasing the dose of aspirin to 325 mg/d or increasing the target INR, depending on bleeding risk. (Level of Evidence: C)"

Class IIb

"2. For patients with a bioprosthetic aortic or mitral valve who have a TIA, ischemic stroke, or systemic embolism despite adequate antiplatelet therapy, the addition of VKA therapy with an INR target of 2.5 (range, 2.0–3.0) may be considered. (Level of Evidence: C)"

Antithrombotic Therapy for Noncardioembolic Stroke or TIA

Antiplatelet Agent

Class I

"1. For patients with noncardioembolic ischemic stroke or TIA, the use of antiplatelet agents rather than oral anticoagulation is recommended to reduce the risk of recurrent stroke and other cardiovascular events. (Level of Evidence: A)"

"2. Aspirin (50–325 mg/d) monotherapy (Level of Evidence: A) or the combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily (Level of Evidence: B) is indicated as initial therapy after TIA or ischemic stroke for prevention of future stroke. (Level of Evidence: A)"

"3. The selection of an antiplatelet agent should be individualized on the basis of patient risk factor profiles, cost, tolerance, relative known efficacy of the agents, and other clinical characteristics. (Level of Evidence: C)"

Class IIa

"1. Clopidogrel (75 mg) monotherapy is a reasonable option for secondary prevention of stroke in place of aspirin or combination aspirin/dipyridamole. (Level of Evidence: B)"

Class IIb

"1. The combination of aspirin and clopidogrel might be considered for initiation within 24 hours of a minor ischemic stroke or TIA and for continuation for 90 days. (Level of Evidence: B)"

"2. For patients who have an ischemic stroke or TIA while taking aspirin, there is no evidence that increasing the dose of aspirin provides additional benefit. Although alternative antiplatelet agents are often considered, no single agent or combination has been adequately studied in patients who have had an event while receiving aspirin. (Level of Evidence: C)"

"3. For patients with a history of ischemic stroke or TIA, AF, and CAD, the usefulness of adding antiplatelet therapy to VKA therapy is uncertain for purposes of reducing the risk of ischemic cardiovascular and cerebrovascular events. Unstable angina and coronary artery stenting represent special circumstances in which management may warrant DAPT/VKA therapy. (Level of Evidence: C)"

Class III (Harm)

"1. The combination of aspirin and clopidogrel, when initiated days to years after a minor stroke or TIA and continued for 2 to 3 years, increases the risk of hemorrhage relative to either agent alone and is not recommended for routine long-term secondary prevention after ischemic stroke or TIA. (Level of Evidence: A)"

Oral Anticoagulant

Class I

"1. For patients with noncardioembolic ischemic stroke or TIA, the use of antiplatelet agents rather than oral anticoagulation is recommended to reduce the risk of recurrent stroke and other cardiovascular events. (Level of Evidence: A)"

Treatments for Stroke Patients With Other Specific Conditions

Aortic Arch Atheroma

Class I

"1. For patients with an ischemic stroke or TIA and evidence of aortic arch atheroma, antiplatelet therapy is recommended. (Level of Evidence: A)"

"2. For patients with an ischemic stroke or TIA and evidence of aortic arch atheroma, statin therapy is recommended. (Level of Evidence: B)"

Class IIb

"1. For patients with ischemic stroke or TIA and evidence of aortic arch atheroma, the effectiveness of anticoagulation with warfarin, compared with antiplatelet therapy, is unknown. (Level of Evidence: C)"

Class III (Harm)

"1. Surgical endarterectomy of aortic arch plaque for the purposes of secondary stroke prevention is not recommended. (Level of Evidence: C)"

Arterial Dissection

Class IIa

"1. For patients with ischemic stroke or TIA and extracranial carotid or vertebral arterial dissection, antithrombotic treatment with either antiplatelet or anticoagulant therapy for at least 3 to 6 months is reasonable. (Level of Evidence: B)"

Class IIb

"1. The relative efficacy of antiplatelet therapy compared with anticoagulation is unknown for patients with ischemic stroke or TIA and extracranial carotid or vertebral arterial dissection. (Level of Evidence: B)"

"2. For patients with stroke or TIA and extracranial carotid or vertebral arterial dissection who have definite recurrent cerebral ischemic events despite medical therapy, endovascular therapy (stenting) may be considered. (Level of Evidence: C)"

"3. Patients with stroke or TIA and extracranial carotid or vertebral arterial dissection who have definite recurrent cerebral ischemic events despite medical therapy and also fail or are not candidates for endovascular therapy may be considered for surgical treatment. (Level of Evidence: C)"

Patent Foramen Ovale

Class I

"1. For patients with an ischemic stroke or TIA and a PFO who are not undergoing anticoagulation therapy, antiplatelet therapy is recommended. (Level of Evidence: B)"

For patients with an ischemic stroke or TIA and both a PFO and a venous source of embolism, anticoagulation is indicated, depending on stroke characteristics.

Class IIa

"1. When anticoagulation is contraindicated, an inferior vena cava filter is reasonable. (Level of Evidence: C)"

Class IIb

"1. There are insufficient data to establish whether anticoagulation is equivalent or superior to aspirin for secondary stroke prevention in patients with PFO. (Level of Evidence: B)"

"2. In the setting of PFO and DVT, PFO closure by a transcatheter device might be considered, depending on the risk of recurrent DVT. (Level of Evidence: C)"

Class III (Harm)

"1. For patients with a cryptogenic ischemic stroke or TIA and a PFO without evidence for DVT, available data do not support a benefit for PFO closure. (Level of Evidence: A)"

Hyperhomocysteinemia

Class III (Harm)

"1. Routine screening for hyperhomocysteinemia among patients with a recent ischemic stroke or TIA is not indicated. (Level of Evidence: C)"

"2. In adults with a recent ischemic stroke or TIA who are known to have mild to moderate hyperhomocysteinemia, supplementation with folate, vitamin B6, and vitamin B12 safely reduces levels of homocysteine but has not been shown to prevent stroke. (Level of Evidence: B)"

Hypercoagulable States

Class I

"1. Antiplatelet therapy is recommended for patients who are found to have abnormal findings on coagulation testing after an initial ischemic stroke or TIA if anticoagulation therapy is not administered. (Level of Evidence: A)"

Class IIb

"1. The usefulness of screening for thrombophilic states in patients with ischemic stroke or TIA is unknown. (Level of Evidence: C)"

"2. Anticoagulation might be considered in patients who are found to have abnormal findings on coagulation testing after an initial ischemic stroke or TIA, depending on the abnormality and the clinical circumstances. (Level of Evidence: C)"

"3. Long-term anticoagulation might be reasonable for patients with spontaneous cerebral venous sinus thrombosis or a recurrent ischemic stroke of undefined origin and an inherited thrombophilia. (Level of Evidence: C)"

Antiphospholipid Antibodies

Class I

"1. For patients with ischemic stroke or TIA who have an antiphospholipid antibody but do not fulfill the criteria for APS, antiplatelet therapy is recommended. (Level of Evidence: B)"

"2. For patients with ischemic stroke or TIA who meet the criteria for the APS but in whom anticoagulation is not begun, antiplatelet therapy is indicated. (Level of Evidence: A)"

Class IIb

"1. For patients with ischemic stroke or TIA who meet the criteria for the APS, anticoagulant therapy might be considered depending on the perception of risk for recurrent thrombotic events and bleeding. (Level of Evidence: C)"

Class III (Harm)

"1. Routine testing for antiphospholipid antibodies is not recommended for patients with ischemic stroke or TIA who have no other manifestations of the APS and who have an alternative explanation for their ischemic event, such as atherosclerosis, carotid stenosis, or AF. (Level of Evidence: C)"

Sickle Cell Disease

Class I

"1. For patients with sickle cell disease and prior ischemic stroke or TIA, chronic blood transfusions to reduce hemoglobin S to <30% of total hemoglobin are recommended. (Level of Evidence: B)"

Class IIa

"1. For adults with sickle cell disease and ischemic stroke or TIA, general treatment recommendations cited elsewhere in this guideline are reasonable with regard to the control of risk factors and the use of antiplatelet agents. (Level of Evidence: B)"

Class IIb

"1. For patients with sickle cell disease and prior ischemic stroke or TIA for whom transfusion therapy is not available or practical, treatment with hydroxyurea may be considered. (Level of Evidence: B)"

Cerebral Venous Sinus Thrombosis

Class IIa

"1. Anticoagulation is reasonable for patients with acute CVST, even in selected patients with intracranial hemorrhage. (Level of Evidence: B)"

"2. In CVST patients without a recognized thrombophilia, it is reasonable to administer anticoagulation for ≥3 months, followed by antiplatelet therapy. (Level of Evidence: C)"

Recommendations During Pregnancy

Class IIa

"1. In the presence of a high-risk condition that would require anticoagulation outside of pregnancy, the following options are reasonable: a. LMWH twice daily throughout pregnancy, with dose adjusted to achieve the LMWH manufacturer’s recommended peak anti-Xa activity 4 hours after injection, or b. Adjusted-dose UFH throughout pregnancy, administered subcutaneously every 12 hours in doses adjusted to keep the midinterval activated partial thromboplastin time at least twice control or to maintain an anti-Xa heparin level of 0.35 to 0.70 U/mL, or c. UFH or LMWH (as above) until the 13th week, followed by substitution of a VKA until close to delivery, when UFH or LMWH is resumed. ( (Level of Evidence: C)"

"2. For pregnant women receiving adjusted-dose LMWH therapy for a high-risk condition that would require anticoagulation outside of pregnancy, and when delivery is planned, it is reasonable to discontinue LMWH ≥24 hours before induction of labor or cesarean section. (Level of Evidence: C)"

"3. In the presence of a low-risk situation in which antiplatelet therapy would be the treatment recommendation outside of pregnancy, low-dose aspirin (50–150 mg/d) is reasonable after the first trimester of pregnancy. (Level of Evidence: B)"

Class IIb

"1. In the presence of a low-risk situation in which antiplatelet therapy would be the treatment recommendation outside of pregnancy, UFH or LMWH, or no treatment may be considered during the first trimester of pregnancy depending on the clinical situation. (Level of Evidence: C)"

Recommendations for Breastfeeding Women

Class IIa

"1. In the presence of a high-risk condition that would require anticoagulation outside of pregnancy, it is reasonable to use warfarin, UFH, or LMWH. (Level of Evidence: C)"

Class IIb

"1. In the presence of a low-risk situation in which antiplatelet therapy would be the treatment recommendation outside of pregnancy, low-dose aspirin use may be considered. (Level of Evidence: C)"

Special Approaches in High-Risk Populations Recommendations

Class I

"1. Monitoring achievement of nationally accepted, evidence-based guidelines on a population-based level is recommended as a basis for improving health-promotion behaviors and reducing stroke healthcare disparities among high-risk groups. (Level of Evidence: C)"

"2. Voluntary hospital-based programs for quality monitoring and improvement are recommended to improve adherence to nationally accepted, evidence-based guidelines for secondary stroke prevention. (Level of Evidence: B)"