Stroke Prevention Guidelines

In 2013, the American Heart Association and American Stroke Association (AHA/ASA) published an expert consensus statement updating the definition of stroke. This statement was endorsed and/or affirmed by the following organizations:

• American Association of Neurological Surgeons Congress of Neurological Surgeons
• American Academy of Neurology

The AHA/ASA classification broadly characterizes stroke into the following four broad subtypes ^[1] :  

• Central nervous system (CNS) infarction (including ischemic stroke and silent infarction)
• Intracerebral hemorrhage (ICH)
• Subarachnoid hemorrhage (SAH)
• Stroke caused by cerebral venous thrombosis

CNS infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on one of the following:

• Pathological, imaging, or other objective evidence of cerebral, spinal cord, or retinal focal ischemic injury in a defined vascular distribution, or
• Clinical evidence of cerebral, spinal cord, or retinal focal ischemic injury based on symptoms persisting ≥24 hours or until death, and other etiologies excluded

Stroke caused by intracerebral hemorrhage is defined as rapidly developing clinical signs of neurological dysfunction attributable to a focal collection of blood within the brain parenchyma or ventricular system. The bleeding is not caused by trauma

Stroke caused by subarachnoid hemorrhage is defined as rapidly developing signs of neurological dysfunction and/or headache because of bleeding into the subarachnoid space (the space between the arachnoid membrane and the pia mater of the brain or spinal cord). The bleeding is not caused by trauma.

Stroke caused by cerebral venous thrombosis is defined as infarction or hemorrhage in the brain, spinal cord, or retina because of thrombosis of a cerebral venous structure. Symptoms or signs caused by reversible edema without infarction or hemorrhage do not qualify as stroke.

Not all strokes will fit into one of those four categories. Stroke, not otherwise specified is defined as an episode of acute neurological dysfunction presumed to be caused by ischemia or hemorrhage, and persisting ≥24 hours or until death, but lacking sufficient evidence to be classified as one of the above.

AHA/ASA recommends against the use of the term “hemorrhagic stroke” because it may refer to both hemorrhage that occurs after CNS infarction or primary ICH or SAH. Instead, the statement suggests that hemorrhagic infarctions, which are characterized by a lack of mass effect, should be considered CNS infarctions, while parenchymal hemorrhages, which are characterized by the presence of mass effect should be considered ICHs.

The International Classification of Diseases (ICD) 10th revision along with its clinical modification (ICD-10-CM) published in 2015, classifies cerebrovascular disorders chiefly into the following categories:

• Transient ischemic attack (TIA) ^[2]
• Cerebral infarction
• ICH
• SAH
• Cerebral thrombosis with infarction

In October 2014, the American Heart Association and American Stroke Association (AHA/ASA) released an update of their 2011 Guidelines for the Primary Prevention of Stroke. ^[3] These guidelines were endorsed and/or affirmed by the following organizations:

• American Association of Neurological Surgeons
• Congress of Neurological Surgeons
• Preventative Cardiovascular Nurses Association
• American Academy of Neurology

The guidelines provide an overview of established and emerging risk factors for stroke and outline risk assessment strategies. The influence of both modifiable and unmodifiable risk factors are discussed, to permit estimation of risk for a first stroke for an individual patient. In general, the use of the AHA/ACC CV Risk Calculator ^[4] is reasonable to alert clinicians and patients to possible risk. When making treatment decisions, however, clinicians need to consider the results in the context of the patient’s overall risk profile.

With evidence that 10 modifiable risk factors accounted for 90% of the risk for stroke, ^[5] the guidelines stress the importance of identifying and providing effective interventions to stroke-prone individuals. Both established and emerging modifiable risk factors and evidence-based recommendations for management are summarized in Table 1, below. ^[3]

Table 1. Recommendations for Stroke Risk Reduction   (Open Table in a new window)

In addition, the guidelines acknowledge that the individual components of the metabolic syndrome can increase stroke risk and should be managed appropriately. Medications and lifestyle changes should be used to treat hypertension and hyperlipidemia and provide glycemic control, as they would for persons with individual risk factors. ^[3]

With regard to antiplatelet agents and aspirin, the guidelines note that although some evidence supports the use of aspirin in the primary prevention of stroke in women, the benefits are small; if opting for aspirin therapy, the potential risks of stroke should outweigh the risks of aspirin use. ^[3]

Diagnosis and management of stroke caused by cerebral venous thrombosis (CVT) was the subject of a 2011 AHA/ASA statement. Primary prevention of CVT has not been the focus of randomized clinical trials, but the AHA/ASA statement suggests that primary prevention strategies for venous thromboembolism in general may have some efficacy with respect to CVT. ^[6]

 

2021 AHA/ASA recommendations

Updated guidelines on the secondary prevention of stroke (in patients with stroke and transient ischemic attack [TIA]) were published in May 2021 by the American Heart Association/American Stroke Association in Stroke. ^{[14, 15]} Among the recommendations is that, whenever possible, diagnostic tests to determine the cause of a first stroke or TIA should be completed within 48 hours after symptomatic onset.

Top 10 key messages

The ischemic stroke/TIA subtype guides prevention strategies. Therefore, the AHA/ASA has grouped their advice by etiologic subtype in a new section with recommendations for post-ischemic stroke diagnostic workup—to define the ischemic stroke etiology (when possible), and to identify treatment targets to reduce the risk of recurrent ischemic stroke.

A key strategy for secondary stroke prevention is multidisciplinary management of, and personalized treatment goals for, vascular risk factors, particularly hypertension, diabetes, lipid levels, and smoking cessation.

Lifestyle factors such as limiting salt intake and/or following a heart-healthy Mediterranean diet are also advised, as well as, when possible, engaging in at least moderate-intensity aerobic activity for at least 10 minutes four times a week or vigorous-intensity aerobic activity for at least 20 minutes twice a week.

Patient lifestyle and behavioral modifications (eg, diet, exercise, medication compliance) require not only the receipt of clinical advice or brochures but also participation in programs that use theoretical models of behavior change, proven techniques, and multidisciplinary support.

Prescribe antithrombotic therapy, including antiplatelets or anticoagulants, in the absence of contraindications. The combination of antiplatelets and anticoagulation is typically not indicated for secondary stroke prevention, and dual antiplatelet therapy (DAT) (taking aspirin plus a second agent to prevent blood clotting) is recommended in the short term and only for specific patients: those with early arriving minor stroke and high-risk TIA or severe symptomatic intracranial stenosis.

Screen for atrial fibrillation (AF), and initiate anticoagulation in the absence of contraindications to reduce recurrent events. If no other cause of stroke can be identified, heart rhythm monitoring for occult AF is often recommended.

Consider carotid endarterectomy or carotid artery stenting for select patients with stenosis of the carotid arteries, such as those with severe stenosis ipsilateral to a nondisabling stroke or TIA who are candidates for intervention.

Aggressive medical management of risk factors and short-term DAT are preferred as first-line therapy for preventing recurrence in patients with severe intracranial stenosis believed to be the cause of first ischemic stroke or TIA, rather than angioplasty and stenting.

It is reasonable to consider percutaneous closure of patent foramen ovale in selected patients: those with younger age who have nonlacunar stroke or no other cause at any age.

No benefit has been found for empirical treatment with anticoagulants or ticagrelor in patients with embolic stroke of uncertain source.

2014 AHA/ASA recommendations

In May 2014, the American Heart Association and American Stroke Association (AHA/ASA) released an update of their 2011 Guidelines for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack. ^[7] These guidelines were endorsed and/or affirmed by the following organizations:

• American Association of Neurological Surgeons
• Congress of Neurological Surgeons
• American Academy of Neurology

As with primary prevention, the guidelines emphasize the importance of blood pressure, cholesterol, weight, and exercise. In addition, new recommendations focus on sleep apnea, carotid disease, atrial fibrillation, aortic arch atherosclerosis, and oral anticoagulants.

The recommendations for risk factor control for all patients with transient ischemic attack (TIA) or ischemic stroke are summarized in Table 2, below. ^[7]

Table 2. Recommendations for Stroke Factor Control (Open Table in a new window)

Large artery atherosclerosis

Based on outcome findings of a meta-analysis of comparative trials, the AHA/ASA guidelines have changed from a class I to a class IIa the recommendation of carotid artery stenting (CAS) as an alternative to carotid endarterectomy (CEA) for symptomatic patients in whom the diameter of the lumen of the internal carotid artery is reduced by >70%, on noninvasive imaging studies, or by >50% on catheter-based imaging or noninvasive imaging with corroboration.

The guidelines also provide a new class IIa recommendation that for older patients (>70 years), outcomes may be better with CEA than withCAS, particularly in patients with arterial anatomy unfavorable for endovascular intervention. In  younger patients, CAS and CEA have comparable outcomes. ^[7]

Recommendations for patients with stroke or TIA attributable to intracranial atherosclerosis include the following:

• For patients with severe stenosis (≥70%) of a major intracranial artery: Within 30 days of the stroke or TIA, the addition of clopidogrel 75 mg/d to aspirin for 90 days (class IIb); stenting with the Wingspan stent system is not recommended as an initial treatment (class III) and angioplasty alone or placement of stents other than Wingspan is considered investigational (class IIb)
• For patients with stenosis (≥50%) of a major intracranial artery: Maintenance of systolic BP below 140 mm Hg and high-intensity statin therapy (class I); however, there is insufficient evidence that clopidogrel alone, the combination of aspirin and dipyridamole, or cilostazol alone is useful (class IIb)
• For patients with stenosis (50% to < 70%) of a major intracranial artery: Angioplasty or stenting is not recommended (class III)

Atrial fibrillation

In addition to the AHA/ASA, the American Academy of Neurology (AAN) and American College of Chest Physicians (ACCP) provide guidelines for the secondary prevention of stroke in patients with atrial fibrillation (AF). ^{[7, 9, 10]} .

Both AHA/ASA and AAN guidelines recommend monitoring for AF in patients who have had an acute ischemic stroke or TIA. The AHA/ASA recommend 30 days of cardiac rhythm monitoring within 6 months of the event, while the AAN recommends outpatient cardiac rhythm monitoring for 1 week or longer. ^{[7, 9]}

2014 AAN guidelines

The AAN guidelines make the following recommendations for selection of patients for antithrombotic therapy ^[9] :

Level B

Patients should be counseled that the decision to use antithrombotics must be made only after the potential benefit from the stroke risk reduction has been weighed against the potential harm from the increased risk for major bleeding, and clinicians should emphasize the important role of judgment and preferences in this decision.

Clinicians should routinely offer anticoagulation to the following:

• Patients with nonvalvular atrial fibrillation (NVAF) and a history of TIA or stroke
• Elderly patients (>75 years) with NVAF who have no history of recent unprovoked bleeding or intracranial hemorrhage

Clinicians might offer oral anticoagulation to patients with NVAF who have dementia or occasional falls. However, clinicians should counsel patients or their families that the risk–benefit ratio of oral anticoagulants is uncertain in patients with NVAF who have moderate to severe dementia or very frequent falls

Clinicians should use a risk stratification scheme to inform their judgment as to which patients with NVAF might benefit more from anticoagulation. However, anticoagulation thresholds suggested by these tools should not be considered definitive indicators of which patients require anticoagulation.

Level C

Clinicians might not offer anticoagulation to patients with NVAF who lack additional risk factors. These patients might reasonably be offered aspirin or no antithrombotic therapy at all.

Level U

Because the risk–benefit ratio of oral anticoagulants in patients with NVAF and end-stage renal disease is unknown, there is insufficient evidence to make recommendations

Oral anticoagulation

The 2012 ACCP guidelines view oral anticoagulation as the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS₂ score of ≥2) For patients at lower levels of risk, however, the ACCP recommends a more individualized approach that takes into consideration patient values and preferences, bleeding risk, and the presence of non-CHADS₂ stroke risk factors. ^[10]

The AHA/ASA also recommends that 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. ^[7]

A comparison of recommendations for selection of oral anticoagulants is provided in Table 3, below ^{[7, 9, 10]} .

Table 3. Guidelines for Selection of Oral Anticoagulants for patients with AF (Open Table in a new window)

Antithrombotic Therapy for Noncardioembolic Stroke

The ACCP guidelines for secondary prevention of noncardioembolic stroke recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended-release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (grade 1A), oral anticoagulants (grade 1B), the combination of clopidogrel plus aspirin (grade 1B), or triflusal (grade 2B). An antiplatelet regimen of clopidogrel or aspirin/extended-release dipyridamole is preferred over aspirin (grade 2B) or cilostazol (grade 2C). ^[11]

The AHA/ASA recommendations for antithrombotic therapy for noncardioembolic stroke include the following:

• Antiplatelet agents rather than oral anticoagulation to reduce the risk of recurrent stroke and other cardiovascular events (class I).
• Selection of an antiplatelet agent individualized on the basis of patient risk factor profiles, cost, tolerance, relative known efficacy of the agents, and other clinical characteristics (class I).
• Aspirin (50–325 mg/d) monotherapy or the combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily as initial therapy (class I)
• Clopidogrel (75 mg) monotherapy is a reasonable option in place of aspirin or combination aspirin/dipyridamole. (class IIa)
• 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 21 days (class IIb)
• The combination of aspirin and clopidogrel 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 (class III).
• 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 (class IIb).

Antithrombotic Therapy for Patent Foramen Ovale

Stroke patients with patent foramen ovale (PFO) do not have a significantly higher risk of recurrent stroke or death compared with those without a PFO, and given the known increased risk of bleeding complications with anticoagulation and the lack of data to demonstrate a benefit in terms of reduction of recurrent ischemic cardiovascular events, ACCP guidelines do not recommend anticoagulation for this population. ^[11]

However, AHA/ASA guidelines give a class I recommendation for anticoagulation in patients with both a PFO and a venous source of embolism. When anticoagulation is contraindicated, an inferior vena cava filter is an option (class IIa). In patients with PFO who are not undergoing anticoagulation therapy, antiplatelet therapy is recommended.(Class I) ^[7]

PFO closure is an alternative to antithrombotic therapy but lacks clinical evidence of effectiveness. Consequently, the ACCP suggests that patients with stroke and PFO be treated with antiplatelet therapy following the recommendations for patients with noncardioembolic stroke. ^[11]

The AHA/ASA recommends against the closing of a PFO in patients who do not have deep vein thrombosis (DVT). For those patient with DVT, closure by transcatheter device can be considered, depending on the risk of recurrent DVT. Like the ACCP, AHA/ASA guidelines recommend antiplatelet therapy. ^[7]

Antithrombotic Therapy and Intracranial Hemorrhage

In general, the ACCP guidelines recommend against long-term use of antithrombotic therapy for secondary prevention of stroke in patients with a history of symptomatic intracranial hemorrhage (ICH) (grade 2C); however, patients who might benefit from antithrombotic therapy are those at relatively low risk of recurrent ICH (eg, with deep hemorrhages) and relatively high risk (>7% per year) of cardiac thromboembolic events (eg, with mechanical heart valves or CHADS₂ score >4). ^[11]

The AHA/ASA guidelines recommend that the decision to restart antithrombotic therapy after ICH related to antithrombotic therapy be individualized based on the risk of subsequent arterial or venous thromboembolism, the risk of recurrent ICH, and the overall status of the patient. Additional recommendations include the following:

• Consider an antiplatelet agent for patients with a comparatively lower risk of cerebral infarction (eg, AF without prior ischemic stroke) and a higher risk of recurrent ICH (eg, elderly patients with lobar ICH or presumed amyloid angiopathy) or with very poor overall neurological function (class IIb)
• For patients who require resumption or initiation of anticoagulation, the optimal timing is uncertain; for most patients, however, waiting ≥1 week might be reasonable (class IIb)

Cerebral Venous Sinus Thrombosis

ACCP guidelines suggest anticoagulation over no anticoagulant therapy during the acute and chronic phases of cerebral venous sinus thrombosis (CVT) (grade 2C).  ^[11]

According to the 2011 AHA/ASA CVT statement, prevention strategies for CVT are focused on venous events such as recurrence of CVT or other venous thromboembolism. Anticoagulation is the mainstay of acute treatment for CVT, and short or extended anticoagulant therapy is often used for secondary prevention after CVT, but no clinical trials have studied this use.

Because patients who have had an episode of CVT are more likely to experience new systemic venous thromboembolism than recurrent CVT CVT, it may be generally reasonable to prevent both by adopting venous thromboembolism prevention guidelines. However, the CVT statement recommends testing patients for prothrombotic conditions 2-4 weeks after completion of acute anticoagulant treatment (if they are not taking warfarin) in order to determine individual thrombosis risk. ^[6]

Aortic Arch Atheroma

In the 2014 updated guidelines, the AHA/ASA added the recommendation that patients with evidence of aortic arch atheroma should receive statin therapy and antiplatelet therapy; however, the effectiveness of warfarin compared to antiplatelet therapy, is unknown. In addition, surgical endarterectomy of the aortic arch plaque for the purposes of secondary stroke prevention is not recommended (class III). ^[7]

In 2014, the American Heart Association/American Stroke Association (AHA/ASA) issued the first guidelines for reducing stroke risk specifically in women. These guidelines have been endorsed and/or affirmed by the following organizations:

• American Association of Neurological Surgeons
• Congress of Neurological Surgeons
• American Academy of Neurology

Risk factors specific to women that are identified in the guidelines include the following:

• Pregnancy
• Preeclampsia
• Gestational diabetes
• Oral contraceptive use
• Postmenopausal hormone use
• Changes in hormone status

In addition, the following risk factors are stronger or more prevalent in women:

• Migraine with aura
• Atrial fibrillation
• Diabetes mellitus
• Hypertension
• Depression
• Psychosocial stress

Given these documented differences in stroke risk between men and women, the guidelines recommend development of woman-specific stroke risk profiles to more accurately reflect a woman’s future risk of stroke than some of the currently available stroke risk scores. ^[12]

Preeclampsia

The AHA/ASA recommendations (class I) for interventions for prevention of preeclampsia are as follows ^[12] :

• Women with chronic primary or secondary hypertension or previous pregnancy-related hypertension should take low-dose aspirin from the 12th week of gestation until delivery
• Consider calcium supplementation (≥1 g/d orally) for women with low dietary intake of calcium (< 600 mg/d)

The AHA/ASA recommendations for interventions formanagement of preeclampsia are as follows ^[12] :

• Severe hypertension should be treated with safe and effective antihypertensive medications, such as methyldopa, labetalol, and nifedipine, with consideration of maternal and fetal side effects (class I)
• Consider treatment of moderate hypertension, although maternal-fetal risk-benefit ratios have not been established (class IIa)
• Atenolol, angiotensin receptor blockers, and direct renin inhibitors are contraindicated in pregnancy and should not be used (class III)

The AHA/ASA recommends that postpartum, women with chronic hypertension should be continued on their antihypertensive regimen, with dosage adjustments to reflect the decrease in volume of distribution and glomerular filtration rate that occurs after delivery. They should also be monitored carefully for the development of postpartum preeclampsia (class IIa).

Because of the increased risk of stroke 1 to 30 years after delivery in women with a history of preeclampsia, evaluate all women starting 6 months to 1 year postpartum, as well as those who are past childbearing age, for a history of preeclampsia/eclampsia and document their history of preeclampsia/eclampsia as a risk factor; evaluate and treat for cardiovascular risk factors including hypertension, obesity, smoking, and dyslipidemia (class IIa).

The ACCP guidelines for venous thromboembolism (VTE), thrombophilia, and antithrombotic therapy during pregnancy offer the following recommendations for the prevention and management of preeclampsia ^[13] :

• For women at risk: Low-dose aspirin throughout pregnancy, starting in the second trimester
• For women with ≥2 miscarriages but without antiphospholipid antibody (APLA) or thrombophilia, antithrombotic prophylaxis is recommended against

Oral Contraception and Postmenopausal Hormone Therapy

The AHA/ASA guidelines note that oral contraceptives (OCs) may be harmful in women with additional risk factors (eg, cigarette smoking, prior thromboembolic events) and in women using OCs, aggressive intervention for stroke risk factors may be reasonable. Measurement of blood pressure before initiation of hormonal contraception is recommended.

In postmenopausal women, neither hormone therapy (conjugated equine estrogen [CEE] with or without medroxyprogesterone) nor selective estrogen receptor modulators (ie, raloxifene, tamoxifen, tibolone) should be used for primary prevention of stroke. ^[12]

Cerebral Venous Thrombosis (CVT)

Because cerebral venous thrombosis (CVT) is related to hormonal factors (primarily oral contraceptives) and pregnancy, over 70% of cases are in women. The greatest risk periods for CVT include the third trimester and the first month postpartum, with 73% of CVT in women occurring in the puerperium. The AHA/ASA guidelines address the management of CVT with the following recommendations ^[12] :

• Screen for potential prothrombotic conditions that may predispose a woman to CVT (eg, use of contraceptives, underlying inflammatory disease, infectious process) in the initial clinical assessment (class I).
• Testing for prothrombotic conditions (protein C, protein S, or antithrombin deficiency; antiphospholipid syndrome; prothrombin G20210A mutation; and factor V Leiden) can be beneficial for the management of patients with CVT. Testing for protein C, protein S, and antithrombin deficiency is indicated 2 to 4 weeks after completion of anticoagulation. There is a very limited value of testing in the acute setting or in patients taking warfarin (class IIa).
• For provoked CVT (associated with a transient risk factor): Vitamin K antagonists may be continued for 3-6 months, with a target international normalized ratio INR) of 2.0 to 3.0 (class IIb).
• For unprovoked CVT: Vitamin K antagonists may be continued for 6 to 12 months, with a target INR of 2.0 to 3.0 (Class IIb).
• For recurrent CVT, INR of 2.0 to 3.0 (Class IIb).
• For CVT during pregnancy: Low-molecular-weight heparin (LMWH) in full anticoagulant doses throughout pregnancy, and LMWH or vitamin K antagonist with a target INR of 2.0 to 3.0 should be continued for ≥6 weeks postpartum (for a total minimum duration of therapy of 6 months) (class I).
• For acute CVT during pregnancy: Full-dose LMWH rather than unfractionated heparin (class IIa).
• Future pregnancy is not contraindicated in women with a history of CVT. Further investigations regarding the underlying cause and a formal consultation with a hematologist or maternal fetal medicine specialist are reasonable (class IIa).
• For women with a history of CVT: prophylaxis with LMWH during future pregnancies and the postpartum period. (class IIa).

Pregnancy

Both the 2014 AHA/ASA guidelines for secondary prevention of stroke and the 2012 ACCP evidence-based guidelines for antithrombotic therapy provide consistent recommendations for treatment of conditions that would require anticoagulation outside of pregnancy. ^{[7, 13]}

For high-risk conditions (class IIa):

• LMWH twice daily throughout pregnancy, with dose adjusted to achieve the LMWH manufacturer’s recommended peak anti-Xa activity 4 hours after injection, or
• Adjusted-dose unfractionated heparin (UFH) throughout pregnancy, administered subcutaneously every 12 hours in doses adjusted to keep the midinterval activated partial thromboplastin time (aPTT) at least twice control or to maintain an anti-Xa heparin level of 0.35 to 0.70 U/mL, or
• UFH or LMWH (as above) until the 13th week, followed by substitution of a vitamin K antagonist (VKA) until close to delivery, when UFH or LMWH is resumed.
• When delivery is planned, discontinue LMWH ≥24 hours before induction of labor or cesarean section (c lass IIa).

For low-risk conditions where antiplatelet therapy would be the treatment recommendation outside of pregnancy (class IIb):

• UFH or LMWH, or no treatment, may be considered during the first trimester of pregnancy depending on the clinical situation (class IIb)
• Low-dose aspirin (50–150 mg/d) after the first trimester of pregnancy (class IIa)

Migraine with Aura

Because higher migraine frequency is associated with stroke risk, the AHA/ASA guidelines advise that treatments to reduce migraine frequency might be reasonable, although evidence is lacking that this treatment reduces the risk of first stroke. Women with migraine headaches with aura should also be encouraged to stop smoking in order to avoid increased risk of stroke ^[12]

Atrial Fibrillation

The AHA/ASA guidelines note that the prevalence of AF increases with age and women have greater life expectancy; thus, an increase in cases of AF in women compared with men is expected as the population ages. Consequently, active screening (in particular of women >75 years of age) in primary care settings, using pulse taking followed by an electrocardiogram (ECG), is a class I recommendation. AF risk stratification tools in AF that account for age- and sex-specific differences in the incidence of stroke are also recommended (class I).

Oral anticoagulation in women aged ≤65 years with AF alone (CHADS2=0 or 1) is not recommended (class III). However, antiplatelet therapy is a reasonable option for selected low-risk women (class IIa). ^[12]

New oral anticoagulants are a useful alternative to warfarin for the prevention of stroke and systemic thromboembolism in women with paroxysmal or permanent AF and prespecified risk factors (according to CHA2DS2-VASc) who do not have any of the following (class I) ^[12] :

• A prosthetic heart valve or hemodynamically significant valve disease
• Severe renal failure (creatinine clearance 15 mL/min)
• Lower weight (< 50 kg)
• Advanced liver disease (impaired baseline clotting function)

Additional recommendations

The AHA/ASA guidelines provide the following additional recommendation for the prevention of stroke in women ^[12] :

• For women with asymptomatic carotid stenosis: Screen for other treatable risk factors for stroke, and institute lifestyle changes and medical therapies as appropriate (class I); prophylactic carotid endarterectomy (CEA) can be useful in highly selected patients (class IIa)
• For women who are to undergo CEA: Aspirin unless contraindicated (class I)
• For women with transient ischemic attack (TIA) or ischemic stroke within the past 6 months and ipsilateral severe (70%–99%) carotid artery stenosis: CEA if the perioperative morbidity and mortality risk is estimated to be < 6% (class I)
• For women with recent TIA or ischemic stroke and ipsilateral moderate (50%–69%) carotid stenosis: CEA depending on patient-specific factors, such as age and comorbidities, if the perioperative morbidity and mortality risk is estimated to be < 6% (class I)
• When CEA is indicated, performing surgery within 2 weeks of TIA or ischemic stroke is reasonable rather than delaying surgery (class IIa)
• For women with diabetes mellitus: Aspirin therapy (75–325 mg/d) unless contraindicated (class IIa)
• For women at high risk (ie, 10-year predicted CVD risk ≥10%) but intolerant of aspirin: Substitute clopidogrel (class I)
• Aspirin therapy (81 mg/d or 100 mg every other day) can be useful in women ≥65 years of age if blood pressure is controlled and the benefit for ischemic stroke prevention is likely to outweigh the risk of gastrointestinal bleeding and hemorrhagic stroke (class IIa); aspirin therapy may be reasonable for women < 65 years of age for ischemic stroke prevention (class IIb)