Note from the National Guideline Clearinghouse (NGC) and the American Heart Association/American Stroke Association (AHA/ASA): The AHA/ASA Writing committee for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack (TIA) has reviewed the results of recent trials that were published after their previous recommendations were issues. The 2 areas in which major new clinical trials have been published are (1) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and (2) the use of statins in the prevention of recurrent stroke. Recommendations that have been changed since the original 2006 guideline are followed by the label (2008 Addendum).
Definitions for the weight of the evidence (A-C) and classes of recommendations (I-III) are provided at the end of the "Major Recommendations" field.
Abbreviations used in the tables are also listed at the end of the "Major Recommendations" field.
Recommendations for Treatable Vascular Risk Factors
| Risk Factor |
Recommendation |
Class/Level of Evidence |
| Hypertension |
Antihypertensive treatment is recommended for prevention of recurrent stroke and other vascular events in persons who have had an ischemic stroke and are beyond the hyperacute period. |
Class I, Level A |
| Because this benefit extends to persons with and without a history of hypertension, this recommendation should be considered for all ischemic stroke and TIA patients. |
Class IIa, Level B |
| An absolute target BP Level and reduction are uncertain and should be individualized, but benefit has been associated with an average reduction of approximately 10/5 mm Hg and normal BP levels have been defined as <120/80 by JNC-7. |
Class IIa, Level B |
| Several lifestyle modifications have been associated with BP reductions and should be included as part of a comprehensive approach antihypertensive therapy. |
Class IIb, Level C |
| Optimal drug regimen remains uncertain; however, available data support the use of diuretics and the combination of diuretics and an ACEI. Choice of specific drugs and targets should be individualized on the basis of reviewed data and consideration, as well as specific patient characteristics (e.g., extracranial cerebrovascular occlusive disease, renal impairment, cardiac disease, and DM). |
Class I, Level A |
| Diabetes |
More rigorous control of blood pressure and lipids should be considered in patients with diabetes. |
Class IIa, Level B |
| Although all major classes of antihypertensives are suitable for the control of BP, most patients will require >1 agent. ACEIs and ARBs are more effective in reducing the progression of renal disease and are recommended as first-choice medications for patients with DM. |
Class I, Level A |
| Glucose control is recommended to near-normoglycemic levels among diabetics with ischemic stroke or TIA to reduce microvascular complications. |
Class I, Level A |
| The goal for Hb A1c should be <7%. |
Class IIa, Level B |
| Cholesterol |
Ischemic stroke or TIA patients with elevated cholesterol, comorbid CAD, or evidence of an atherosclerotic origin should be managed according to NCEP III guidelines, which include lifestyle modification, dietary guidelines, and medication recommendations. |
Class I, Level A |
| Statin agents are recommended, and the target goal for cholesterol lowering for those with CHD or symptomatic atherosclerotic disease is an LDL-C of <100 mg/dL. An LDL-C <70 mg/dL is recommended for very-high-risk persons with multiple risk factors. |
Class I, Level A |
| On the basis of the SPARCL trial, administration of statin therapy with intensive lipid-lowering effects is recommended for patients with atherosclerotic ischemic stroke or TIA and without known CHD to reduce the risk of stroke and cardiovascular events. (2008 Addendum) |
Class I, Level B |
| Ischemic stroke or TIA patients with low HDL cholesterol may be considered for treatment with niacin or gemfibrozil. |
Class IIb, Level B |
Recommendations for Modifiable Behavioral Risk Factors
| Risk Factor |
Recommendation |
Class/Level of Evidence |
| Smoking |
All ischemic stroke or TIA patients who have smoked in the past year should be strongly encouraged not to smoke. |
Class I, Level C |
| Avoid environmental smoke. |
Class IIa, Level C |
| Counseling, nicotine products, and oral smoking cessation medications have been found to be effective for smokers. |
Class IIa, Level B |
| Alcohol |
Patients with prior ischemic stroke or TIA who are heavy drinkers should eliminate or reduce their consumption of alcohol. |
Class I, Level A |
| Light to moderate levels of <2 drinks per day for men and 1 drink per day for nonpregnant women may be considered. |
Class IIb, Level C |
| Obesity |
Weight reduction may be considered for all overweight ischemic stroke or TIA patients to maintain the goal of a BMI of 18.5 to 24.9 kg/m2 and a waist circumference of <35 inches for women and <40 inches for men. Clinicians should encourage weight management through an appropriate balance of caloric intake, physical activity, and behavioral counseling. |
Class IIb, Level C |
| Physical activity |
For those with ischemic stroke or TIA who are capable of engaging in physical activity, at least 30 minutes of moderate-intensity physical exercise most days may be considered to reduce risk factors and comorbid conditions that increase the likelihood of recurrence of stroke. For those with disability after ischemic stroke, a supervised therapeutic exercise regimen is recommended. |
Class IIb, Level C |
Recommendations for Interventional Approaches to Patients With Stroke Caused by Large-Artery Atherosclerotic Disease
| Risk Factor |
Recommendation |
Class/Level of Evidence |
| Extracranial carotid disease |
For patients with recent TIA or ischemic stroke within the last 6 months and ipsilateral severe (70 to 99%) carotid artery stenosis, CEA is recommended by a surgeon with a perioperative morbidity and mortality of <6%. |
Class I, Level A |
| For patients with recent TIA or ischemic stroke and ipsilateral moderate (50 to 69%) carotid stenosis, CEA is recommended, depending on patient-specific factors such as age, gender, comorbidities, and severity of initial symptoms. |
Class I, Level A |
| When degree of stenosis is <50%, there is no indication for CEA. |
Class III, Level A |
| When CEA is indicated, surgery within 2 weeks rather than delayed surgery is suggested. |
Class IIa, Level B |
| Among patients with symptomatic severe stenosis (>70%) in whom the stenosis is difficult to access surgically, 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 not inferior to endarterectomy and may be considered. |
Class IIb, Level B |
| CAS is reasonable when performed by operators with established periprocedural morbidity and mortality rates of 4 to 6%, similar to that observed in trials of CEA and CAS. |
Class IIa, Level B |
| Among patients with symptomatic carotid occlusion, EC/IC bypass surgery is not routinely recommended. |
Class III, Level A |
| Extracranial vertebrobasilar disease |
Endovascular treatment of patients with symptomatic extracranial vertebral stenosis may be considered when patients are having symptoms despite medical therapies (antithrombotics, statins, and other treatments for risk factors). |
Class IIb, Level C |
| Intracranial arterial disease |
The usefulness of endovascular therapy (angioplasty and/or stent placement) is uncertain for patients with hemodynamically significant intracranial stenoses who have symptoms despite medical therapies (antithrombotics, statins, and other treatments for risk factors) and is considered investigational. |
Class IIb, Level C |
Recommendations for Patients with Cardioembolic Stroke Types
| Risk Factor |
Recommendation |
Class/Level of Evidence |
| AF |
For patients with ischemic stroke or TIA with persistent or paroxysmal (intermittent) AF, anticoagulation with adjusted-dose warfarin (target INR, 2.5; range, 2.0-3.0) is recommended. |
Class I, Level A |
| In patients unable to take oral anticoagulants, aspirin 325 mg/d is recommended. |
Class I, Level A |
| Acute MI and LV thrombus |
For patients with an ischemic stroke caused by an acute MI in whom LV mural thrombus is identified by echocardiography or another form of cardiac imaging, oral anticoagulation is reasonable, aiming for an INR of 2.0 to 3.0 for at least 3 months and up to 1 year. |
Class IIa, Level B |
| Aspirin should be used concurrently for the ischemic CAD patient during oral anticoagulant therapy in doses up to 162 mg/d, preferably in the enteric-coated form. |
Class IIa, Level A |
| Cardiomyopathy |
For patients with ischemic stroke or TIA who have dilated cardiomyopathy, either warfarin (INR, 2.0 to 3.0) or antiplatelet therapy may be considered for prevention of recurrent events. |
Class IIb, Level C |
| Valvular heart disease |
| Rheumatic mitral valve disease |
For patients with ischemic stroke or TIA who have rheumatic mitral valve disease, whether or not AF is present, long-term warfarin therapy is reasonable, with a target INR of 2.5 (range, 2.0-3.0). |
Class IIa, Level C |
| Antiplatelet agents should not be routinely added to warfarin in the interest of avoiding additional bleeding risk. |
Class III, Level C |
| For ischemic stroke or TIA patients with rheumatic mitral valve disease, whether or not AF is present, who have a recurrent embolism while receiving warfarin, adding aspirin (81 mg/d) is suggested. |
Class IIa, Level C |
| MVP |
For patients with MVP who have ischemic stroke or TIAs, long-term antiplatelet therapy is reasonable. |
Class IIa, Level C |
| MAC |
For patients with ischemic stroke or TIA and MAC not documented to be calcific, antiplatelet therapy may be considered. |
Class IIb, Level C |
| Among patients with mitral regurgitation resulting from MAC without AF, antiplatelet or warfarin therapy may be considered. |
Class IIb, Level C |
| Aortic valve disease |
For patients with ischemic stroke or TIA and aortic valve disease who do not have AF, antiplatelet therapy may be considered. |
Class IIa, Level C |
| Prosthetic heart valves |
For patients with ischemic stroke or TIA who have modern mechanical prosthetic heart valves, oral anticoagulants are recommended, with an INR target of 3.0 (range, 2.5-3.5). |
Class I, Level B |
| For patients with mechanical prosthetic heart valves who have an ischemic stroke or systemic embolism despite adequate therapy with oral anticoagulants, aspirin 75 to 100 mg/d, in addition to oral anticoagulants, and maintenance of the INR at a target of 3.0 (range, 2.5-3.5) is reasonable. |
Class IIa, Level B |
| For patients with ischemic stroke or TIA who have bioprosthetic heart valves with no other source of thromboembolism, anticoagulation with warfarin (INR, 2.0-3.0) may be considered. |
Class IIb, Level C |
Recommendations for Antithrombotic Therapy for Noncardioembolic Stroke or TIA (Oral Anticoagulant and Antiplatelet Therapies)
| Recommendation |
Class/Level of Evidence |
| For patients with noncardioembolic ischemic stroke or TIA, antiplatelet agents rather than oral anticoagulation are recommended to reduce the risk of recurrent stroke and other cardiovascular events. |
Class I, Level A |
| Aspirin (50 to 325 mg/d) monotherapy, the combination of aspirin and extended-release dipyridamole, and clopidogrel monotherapy are all acceptable options for initial therapy.* (2008 Addendum) |
Class I, Level A |
| The combination of aspirin and extended-release dipyridamole is recommended over aspirin alone. (2008 Addendum) |
Class I, Level B |
| Clopidogrel may be considered over aspirin alone on the basis of direct-comparison trials. |
Class IIb, Level B |
| For patients allergic to aspirin, clopidogrel is reasonable. |
Class IIa, Level B |
| The addition of aspirin to clopidogrel increases the risk of hemorrhage. Combination therapy of aspirin and clopidogrel is not routinely recommended for ischemic stroke or TIA patients unless they have a specific indication for this therapy (i.e., coronary stent or acute coronary syndrome). |
Class III, Level A |
*For patients who have an ischemic cerebrovascular event while taking aspirin, there is no evidence that increasing the dose of aspirin provides additional benefit. Although alternative antiplatelet agents are often considered for noncardioembolic patients, no single agent or combination has been well studied in patients who have had an event while receiving aspirin.
Recommendations for Stroke Patients With Other Specific Conditions
| Risk Factor |
Recommendation |
Class/Level of Evidence |
| Arterial dissection |
For patients with ischemic stroke or TIA and arterial dissection, warfarin for 3 to 6 months or antiplatelet agents are reasonable. |
Class IIa, Level B |
| Beyond 3 to 6 months, long-term antiplatelet therapy is reasonable for most ischemic stroke or TIA patients. Anticoagulant therapy beyond 3 to 6 months may be considered among patients with recurrent ischemic events. |
Class IIb, Level C |
| For patients who have definite recurrent ischemic events despite antithrombotic therapy, endovascular therapy (stenting) may be considered. |
Class IIb, Level C |
| Patients who fail or are not candidates for endovascular therapy may be considered for surgical treatment. |
Class IIb, Level C |
| Patent foramen ovale |
For patients with an ischemic stroke or TIA and a PFO, antiplatelet therapy is reasonable to prevent a recurrent event. |
Class IIa, Level B |
| Warfarin is reasonable for high-risk patients who have other indications for oral anticoagulation such as those with an underlying hypercoagulable state or evidence of venous thrombosis. |
Class IIa, Level C |
| Insufficient data exist to make a recommendation about PFO closure in patients with a first stroke and a PFO. PFO closure may be considered for patients with recurrent cryptogenic stroke despite medical therapy. |
Class IIb, Level C |
| Hyperhomocysteinemia |
For patients with an ischemic stroke or TIA and hyperhomocysteinemia (levels >10 micromol/L), daily standard multivitamin preparations are reasonable to reduce the level of homocysteine, given their safety and low cost. However, there is no evidence that reducing homocysteine levels will lead to a reduction of stroke occurrence. |
Class I, Level A |
| Hypercoagulable states |
| Inherited thrombophilias |
Patients with an ischemic stroke or TIA with an established inherited thrombophilia should be evaluated for deep venous thrombosis, which is an indication for short- or long-term anticoagulant therapy, depending on the clinical and hematologic circumstances. |
Class IIa, Level A |
| Patients should be fully evaluated for alternative mechanisms of stroke. |
Class IIa, Level C |
| In the absence of venous thrombosis, long-term anticoagulation or antiplatelet therapy is reasonable. |
|
| Patients with a history of recurrent thrombotic events may be considered for long-term anticoagulation. |
Class IIb, Level C |
| Antiphospholipid antibody syndrome |
For cases of cryptogenic ischemic stroke or TIA and positive APL antibodies, antiplatelet therapy is reasonable. |
Class IIa, Level B |
| For patients with ischemic stroke or TIA who meet the criteria for the APL antibody syndrome with venous and arterial occlusive disease in multiple organs, miscarriages, and livedo reticularis, oral anticoagulation with a target INR of 2 to 3 is reasonable. |
Class IIa, Level B |
| Sickle-cell disease |
For adults with SCD and ischemic stroke or TIA, general treatment recommendations cited above are applicable with regard to the control of risk factors and use of antiplatelet agents. |
Class IIa, Level B |
| Additional therapies that may be added include regular blood transfusion to reduce Hb S to <30 to 50% of total Hb, hydroxyurea, or bypass surgery in cases of advanced occlusive disease. |
Class IIb, Level C |
| Cerebral venous sinus thrombosis |
For patients with cerebral venous sinus thrombosis, UFH or LMWH is reasonable even in the presence of hemorrhagic infarction. |
Class IIa, Level B |
| Continuation of anticoagulation with an oral anticoagulant agent is reasonable for 3 to 6 months, followed by antiplatelet therapy. |
Class IIa, Level C |
| Pregnancy |
For pregnant women with an ischemic stroke or TIA and high-risk thromboembolic conditions such as known coagulopathy or mechanical heart valves, the following options may be considered:
- Adjusted-dose UFH throughout pregnancy such as a subcutaneous dose every 12 h with APTT monitoring
- Adjusted-dose LMWH with factor Xa monitoring throughout pregnancy
- UFH or LMWH until week 13, followed by warfarin until the middle of the third trimester, when UFH or LMWH is then reinstituted until delivery.
|
Class IIb, Level C |
| Pregnant women with lower-risk conditions may be considered for treatment with UFH or LMWH in the first trimester, followed by low-dose aspirin for the remainder of the pregnancy. |
Class IIb, Level C |
| Postmenopausal HRT |
For women with stroke or TIA, postmenopausal HRT is not recommended. |
Class III, Level A |
| Cerebral hemorrhage |
For patients who develop an ICH, SAH, or SDH, all anticoagulants and antiplatelets should be discontinued during the acute period for at least 1 to 2 weeks after the hemorrhage and the anticoagulant effect reversed immediately with appropriate agents (i.e., vitamin K, FFP). |
Class III, Level B |
| For patients who require anticoagulation soon after a cerebral hemorrhage, intravenous heparin may be safer than oral anticoagulation. Oral anticoagulants may be resumed after 3 to 4 weeks, with rigorous monitoring and maintenance of INRs in the lower end of the therapeutic range. |
Class IIb, Level C |
| Special circumstances: |
|
Anticoagulation should not be resumed after an SAH until the ruptured aneurysm is definitively secured.
|
Class III, Level C |
Patients with lobar ICHs or microbleeds and suspected CAA on MRI may be at a higher risk for recurrent ICH if anticoagulation needs to be resumed.
|
Class IIb, Level C |
For patients with hemorrhagic infarction, anticoagulation may be continued, depending on the specific clinical scenario and underlying indication for anticoagulant therapy.
|
Class IIb, Level C |
Recommendations for Special Approaches for Implementing Guidelines and Their Use in High-Risk Populations
- To prevent underutilization or disparities in the use of therapies recommended in national guidelines, the guideline development and distribution process should recognize and incorporate strategies for increased implementation (Class I, Level of Evidence B).
- It is reasonable that intervention strategies emphasize improved access to care for the aged, underserved, and ethnic populations by addressing economic barriers (e.g., coverage for services required), geographic barriers (e.g., expanded use of telemedicine), and a multidisciplinary approach to increase patient and healthcare provider compliance with guidelines and practice parameters (Class IIa, Level of Evidence B).
Abbreviations:
ACEI, angiotensin-converting enzyme inhibitor
AF, atrial fibrillation
APL, antiphospholipid
APTT, activated partial thromboplastin time
ARB, angiotensin receptor blocker
BMI, body mass index
BP, blood pressure
CAA, cerebral amyloid angiopathy
CAD, coronary artery disease
CAS, carotid artery balloon angioplasty and stenting
CEA, carotid endarterectomy
CHD, coronary heart disease
DM, diabetes mellitus
EC/IC, extracranial-intracranial
FFP, fast frozen plasma
Hb A1c, hemoglobin A1c (glycosylated hemoglobin)
Hb S, hemoglobin S formation
HDL-C, high-density lipoprotein-cholesterol
HRT, hormone replacement therapy
ICH, intracerebral hemorrhage
INR, international normalized ratio
JNC-7, Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure
LDL-C, low-density lipoprotein-cholesterol
LMWH, low-molecular weight heparin
LV, left ventricular
MAC, mitral annular calcification
MI, myocardial infarction
MRI, magnetic resonance imaging
MVP, mitral valve prolapse
NCEP, National Cholesterol Education Program
PFO, patent foramen ovale
SAH, subarachnoid hemorrhage
SCD, sickle-cell disease
SDH, subdural hematoma
SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial
TIA, transient ischemic attack
UFH, unfractionated heparin
Definitions:
Levels of Evidence
Level of Evidence A: Data derived from multiple randomized clinical trials
Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies
Level of Evidence C: Expert opinion or case studies
Strength of Recommendations
Class I: Conditions for which there is evidence and/or general agreement that the procedure or treatment is useful and effective
Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment
Class IIa: Weight of evidence or opinion is in favor of the procedure or treatment.
Class IIb: Usefulness/efficacy is less well established by evidence or opinion.
Class III: Conditions for which there is evidence and/or general agreement that a procedure or treatment is not useful/effective and in some cases may be harmful
