Stroke Prevention Guidelines 

Updated: Jan 11, 2016
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Classification of Stroke

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
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Primary Prevention

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)

Established Risk Factor Recommendation Category
Hypertension Regular blood pressure (BP) screening; appropriate hypertension treatment.



Prehypertension (systolic BP of 120-139 mm Hg or diastolic BP of 80-89 mm Hg): Perform annual BP screening and lifestyle modifications



Hypertension: Treat to target <140/90 mm Hg; BP reduction is more important than choice of agent in lowering stroke risk; individualize therapy. Home self-monitoring of blood pressure in hypertensive patients



Class I
Physical Inactivity Healthy adults: moderate- to vigorous-intensity aerobic activity at least 40 minutes per day, 3-4 days per week Class I
Dyslipidemia Lifestyle interventions



High 10-year cardiovascular risk: Initiate statin therapy



Class I
Low high-density lipoprotein cholesterol or high lipoprotein (Lp)(a): Consider niacin, although efficacy in stroke prevention not established



Hypertriglyceridemia: Consider fibric acid derivatives, although efficacy in stroke prevention not established



If statin-intolerant, consider other lipid-lowering therapies, although efficacy in stroke prevention not established



Class IIb
Diet and Nutrition Reduced sodium and increased potassium intake; DASH-style diet rich in fruits and vegetables Class I
Consider Mediterranean diet supplemented with nuts Class IIa
Obesity Weight reduction in overweight and obese individuals Class I
Diabetes Mellitus Type 1 or type 2 diabetes: Control BP, per AHA/ACC/CDC Advisory to target <140/90 mm Hg; Treat adults with diabetes with a statin, especially in case of additional risk factors Class I
Usefulness of aspirin for primary stroke prevention in those with diabetes but a low 10-year risk for cardiovascular disease is unclear Class IIb
Add-on fibrate in those with diabetes is not useful in reducing stroke risk Class III
Smoking Counseling plus drug therapy for smokers; maintain abstinence in those who have never smoked Class I
Community-wide or statewide bans on smoking in public spaces are reasonable Class IIa
Atrial Fibrillation Valvular AF and high stroke risk (CHA2DS2-VASc score ≥ 2): Initiate long-term warfarin therapy; target international normalized ratio (INR), 2.0-3.0



Nonvalvular AF, CHA2DS2-VASc score ≥2, and low risk for hemorrhagic complications: Individualize care and consider warfarin, dabigatran, apixaban, or rivaroxaban



Class I
AF screening in the primary care setting in those older than 65 years



Nonvalvular AF and CHA2DS2-VASc score of 0: reasonable to omit antithrombotic therapy



Class IIa
Nonvalvular AF, CHA2DS2-VASc score 1, and low risk for hemorrhagic complications: No antithrombotic therapy, anticoagulant therapy, or aspirin therapy can be considered; selection of antithrombotic agent should be individualized on the basis of patient risk factors



High-risk patients with AF who are unsuitable for anticoagulation: Consider left atrial appendage closure, if performed at a center with a low complication rate



Class IIb
Other Cardiac Conditions Mitral stenosis and prior embolic event: anticoagulation



Mitral stenosis and left atrial thrombus: anticoagulation



Aortic valve replacement with bileaflet mechanical or current-generation, single-tilting-disk prostheses plus no risk factors: warfarin (INR 2.0-3.0) and low-dose aspirin



Mechanical aortic valve replacement and risk factors(ie, AF, previous thromboembolism, left ventricular dysfunction, and hypercoagulable state): warfarin (INR 2.5-3.5) and low-dose aspirin



Mitral valve replacement with any mechanical valve: warfarin (INR 2.5-3.5) and low-dose aspirin



Atrial myxomas: surgical excision



Symptomatic fibroelastomas and those >1 cm or that appear mobile: surgical intervention



Class I
Aortic or mitral valve replacement with a bioprosthesis: aspirin and warfarin (INR 2.0-3.0) are reasonable



Heart failure but no AF or previous thromboembolic event:  anticoagulants or antiplatelets are reasonable



ST-segment elevation myocardial infarction (STEMI) and asymptomatic left ventricular mural thrombi:  vitamin K antagonist therapy is reasonable



Class IIa
Asymptomatic patients with severe mitral stenosis and left atrial dimension ≥ 55 mm by echo:  consider anticoagulation



Severe mitral stenosis, an enlarged left atrium, and spontaneous contrast on echo: consider anticoagulation



STEMI and anterior apical akinesis or dyskinesis: consider anticoagulation



Class IIb
Patent foramen ovale (PFO): Antithrombotic therapy and catheter-based closure are not recommended for primary stroke prevention Class III
Carotid Artery Stenosis Asymptomatic carotid stenosis: statin plus daily aspirin; screen for and manage other stroke risk factors



Carotid endarterectomy (CEA): peri- and postoperative aspirin, unless contraindicated



Class I
Asymptomatic with >70% stenosis:  consider CEA if perioperative risk for stroke, MI, and death is low (<3%)



>50% stenosis: repeat duplex ultrasonography annually to assess progression, regression, and treatment response



Class IIa
Consider prophylactic stenting in highly selected patients with asymptomatic stenosis (≥60% by angiography or ≥70% by validated Doppler ultrasonography)



Asymptomatic, but high risk for CEA or carotid artery stenting complications: effectiveness of revascularization vs medical therapy is not well established



Class IIb
Screening low-risk populations for asymptomatic stenosis is not recommended Class III
Sickle Cell Disease Children with sickle cell disease (SCD): transcranial Doppler (TCD) screening started at age 2 years, then annually through age 16 years



Children with increased stroke risk: transfusion therapy targeting hemoglobin S <30%



Class I
Screen younger children and those with borderline abnormal TCD flow velocities more frequently; continued transfusion is probably reasonable, even after TCD velocities revert to normal Class IIa
High stroke risk and unable or unwilling to be treated with periodic transfusions:  consider hydroxyurea or bone marrow transplantation Class IIb
MRI and magnetic resonance angiography criteria for selecting patients for primary stroke prevention with transfusion are not established; therefore, they are not recommended in place of TCD for this purpose Class III
Emerging Risk Factor
Migraine Women with migraine plus aura: smoking cessation Class I
Women with active migraines plus aura: consider alternatives to oral contraceptives



Consider treatments that reduce migraine frequency



Class IIb
PFO closure not indicated for stroke prevention Class III
Alcohol Consumption Heavy drinkers:  reduce or stop consumption Class I
Persons who continue drinking: ≤2 drinks/day for men; ≤1 drink/day for nonpregnant women Class IIb
Drug Abuse Referral to therapeutic/rehabilitation program Class IIa
Sleep-Disordered Breathing Although no randomized trial data exist demonstrating effectiveness  for primary stroke prevention, screening and treatment of sleep apnea may be considered Class IIb
Hyperhomocysteinemia Although effectiveness has not been established, B-complex vitamins may be considered Class IIb
Elevated Lp(a) Some genetic and epidemiologic studies suggest that Lp(a) is a risk factor for cardiovascular disease, including stroke and niacin may be considered Class IIb
Hypercoagulability Usefulness of genetic screening to detect inherited hypercoagulability for stroke prevention is not well established



Asymptomatic patients with hereditary or acquired thrombophilia: Usefulness of specific treatments for stroke prevention is not well established



Class IIb
Persistently antiphospholipid antibody–positive patients: Low-dose aspirin is not indicated Class III
Inflammation and Infection Chronic inflammatory conditions (ie, rheumatoid arthritis and systemic lupus erythematosus): consider these patients to have increased stroke risk; enhanced risk factor measurement and control. Class I
Annual flu vaccine can be useful Class IIa
Measurement of inflammatory markers such as hs-CRP or lipoprotein-associated phospholipase A2 in patients without CVD may be considered to identify patients who may be at increased risk of stroke, although their usefulness in routine clinical practice is not well established



High-sensitivity C-reactive protein (hs-CRP) >2 mg/dL: consider statin therapy



Class IIb
Antibiotics for chronic infections as means to prevent stroke are not recommended Class III

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]

 

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Secondary Prevention

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)

Established Risk Factor Recommendation Category
Hypertension Initiate BP therapy 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



Resume BP therapy for patients with known hypertension who have had an ischemic stroke or TIA and are beyond the first several days



The optimal drug is uncertain because direct comparisons between regimens are limited. Diuretics or the combination of diuretics and an angiotensin-converting enzyme inhibitor is useful



Class I
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 Class IIa
Initiation of therapy for patients with BP <140 mm Hg systolic and <90 mm Hg diastolic is of uncertain benefit



For patients with a recent lacunar stroke, an SBP of <130 mm  Hg may be a reasonable target



Class IIb
Dyslipidemia Statin therapy with intensive lipid-lowering effects in patients with ischemic stroke or TIA presumed to be of atherosclerotic origin



Patients with ischemic stroke or TIA and other comorbid ASCVD should be managed according to the 2013 ACC/AHA cholesterol guidelines, [8] which include lifestyle modification, dietary recommendations, and medication recommendations



Class I
Diabetes Mellitus Glycemic control and cardiovascular risk factor management according to current guidelines from the American Diabetes Association for patients with DM or pre-DM Class I
All patients should probably be screened for DM with testing of fasting plasma glucose, HbA1c, or an oral glucose tolerance test; HbA1c may be more accurate than other screening tests in the immediate postevent period Class IIa
Obesity The usefulness of weight loss in patients with a recent TIA or ischemic stroke and obesity is uncertain Class IIb
Metabolic Syndrome For patients classified as having the metabolic syndrome, management should focus on counseling for lifestyle modification (diet, exercise, and weight loss) for vascular risk reduction



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



Class I
Usefulness of screening for the metabolic syndrome after stroke is unknown Class IIb
Physical Inactivity Patients capable of engaging in physical activity: moderate- to vigorous-intensity aerobic activity at least 40 minutes per day, 3-4 days per week; referral to a comprehensive, behaviorally oriented program is reasonable Class IIa
Patients with disability after ischemic stroke: consider supervision by a healthcare professional such as a physical therapist or cardiac rehabilitation professional, at least on initiation of an exercise regimen Class IIb
Diet and Nutrition Patients with signs of undernourishment:  referral for individualized counseling Class I
Nutritional assessment is reasonable



Reduce sodium intake to >2.4 g/d. Further reduction to <1.5 g/d is associated with even greater BP reduction



Mediterranean diet over low-fat diet.



Class IIa
Routine vitamin supplements are not recommended Class III
Sleep-Disordered Breathing Screening and treatment of sleep apnea may be considered Class IIb
Smoking Counseling plus drug therapy for smokers Class I
Avoidance of environmental (passive) tobacco smoke Class IIa
Alcohol Consumption Heavy drinkers:  reduce or stop consumption Class I
Persons who continue drinking: ≤2 drinks/day for men; ≤1 drink/day for nonpregnant women Class IIb

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]

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)

Recommendation AHA/ASA (2014) AAN (2014) ACCP (2012)
For patients 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) Class I    
VKA therapy, apixaban, and dabigatran are all indicated for the prevention of recurrent stroke in patients with NVAF, whether paroxysmal or permanent Class I    
To reduce the risk of stroke or subsequent stroke in patients with NVAF judged to require oral anticoagulants, clinicians should choose one of the following options:



  • Warfarin, target INR 2.0–3.0
See the list below:



  • Dabigatran 150 mg twice daily (if creatinine clearance [CrCl] >30 mL/min)
See the list below:



  • Rivaroxaban 15 mg/d (if CrCl 30–49 mL/min) or 20 mg/d
See the list below:



  • Apixaban 5 mg twice daily (if serum creatinine <1.5 mg/dL) or 2.5 mg twice daily (if patient has two of the following three: serum creatinine >1.5 to <2.5 mg/dL, body weight <60 kg, age ≥80 y)
See the list below:



  • Triflusal 600 mg plus acenocoumarol, target INR 1.25–2.0 (patients at moderate stroke risk, mostly in developing countries)
  Level B  
For patients who are unable to take oral anticoagulants, aspirin alone is recommended Class I    
Rivaroxaban is reasonable for the prevention of recurrent stroke in patients with NVAF Class IIa    
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 Class IIb    
The addition of clopidogrel to aspirin therapy, compared with aspirin therapy alone, might be reasonable Class IIb    
Patients taking warfarin whose condition is well controlled might continue warfarin treatment rather than switch to treatment with a new oral anticoagulant   Level C  
Administer dabigatran, rivaroxaban, or apixaban to patients at higher risk of intracranial bleeding   Level B  
Offer apixaban to patients unsuitable for being treated, or unwilling to be treated, with warfarin   Level B  
Where apixaban is unavailable, clinicians might offer dabigatran or rivaroxaban   Level C  
Offer dabigatran, rivaroxaban, or apixaban to patients unwilling or unable to submit to frequent periodic testing of INR levels   Level B  
Oral anticoagulation preferred over aspirin or combination therapy with aspirin and clopidogrel     Grade 1B
For patients taking oral anticoagulation, dabigatran 150 mg bid preferred over adjusted-dose VKA therapy (target range, 2.0-3.0)     Grade 2B
For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns about major bleeding), combination therapy with aspirin and clopidogrel is preferred over aspirin alone     Grade 1B
CAD=coronary artery disease; INR=International Normalized Ratio; NVAF=nonvalvular atrial fibrillation; TIA=transient ischemic attack; VKA=vitamin K antagonist

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]

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Prevention of Stroke in Women

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)
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