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A. Primary Risk Factors [1] navigator

  1. In USA in 2005, >750,000 strokes occurred [31]
  2. Incidence of stroke has decreased over past 50 years, but lifetime incidence unchanged [31]
  3. Previous stroke is highest risk for recurrent stroke
  4. Stroke risk is increased by the following (X=fold):
    1. Hypertension (HTN): 3-5X
    2. Physical inactivity: 2.7X
    3. Obesity: 1.8-2.4X
    4. Elevated total cholesterol (Chol): 1.8-2.5X
    5. Elevated HDL Chol in elderly associated with reduced risk of ischemic stroke [17]
    6. Smoking: 1.5X
    7. Asymptomatic carotid stenosis: 2.0X
    8. Alcohol intake >5 drinks per day: 1.6X
    9. Atrial fibrillation (AFib): valvular 17X, non-valvular 5X
  5. Evolving Risk Factors
    1. Elevated homocysteine levels associated with 1.4-2X risk in elderly persons [4]
    2. Elevated levels (>373mg/dL) of plasma fibrinogen predict risk of stroke [5]
    3. Hormone replacement therapy (HRT) assocated with 1.2X risk [6]
    4. Noncerebrovascular atherosclerotic disease
    5. Sleep Apnea / Hypopnea - risk increased ~3X [7]
    6. Cardiac Abnormalitites
    7. Surgery - particularly cardiac surgery
  6. Many stroke risk factors are classical cardiovascular (CV) risk factors

B. Risk For Stroke with Prior Cerebrovascular Eventnavigator

  1. Transient Ischemic Attack (TIA) [13,37,38]
    1. Defined as focal deficit with return of function within 24 hours
    2. High risk for full stroke: 5% have stroke within 1 day, 5% more within 3 months
  2. Survivors of TIA or Minor Stroke [13,28,34]
    1. Risk of recurrent stroke ~10% at 90 days [34]
    2. 10 year risk of death ~43%
    3. Age >65 years, diabetes, and claudication have worse prognosis
    4. 10 year risk of any vascular event 44%
    5. Treatment using existing modalities within 1 day (versus usual 3-20 days) after TIA or minor stroke reduces risk of recurrent stroke at 90 days from 10.3% to 2.1% [34]
  3. ABCD Score for Stroke Risk within 7 Days after TIA [33]
    1. Six (6) point system for likelihood of stroke after TIA
    2. A=Age >60: 1 point
    3. B=Blood Presusre (systolic >139 or diastolic >89): 1 point
    4. C=Clinical features: unilateral weakness=2, speech problem without weekness=1 point
    5. D=Duration of sympoms (minutes): >59=2, 10-59=1 point
    6. With ABCD scores 0-4, risk of stroke was <95% within 7 days

C. Overview of Stroke Prevention Measures [1,2,13] navigator

  1. LDL Cholesterol (Chol) Reduction (see below)
    1. Treatment with statins (HMG-CoA reductase inhibitors) is cornerstone of stroke prevention
    2. Overall, statins are probably the most effective stroke preventing agents [13]
    3. Statins reduce both initial and recurrent strokes [19]
    4. Elevated HDL levels in elderly associated with reduced risk of ischemic stroke [17]
  2. Smoking cessation
  3. Physical Activity and Exercise
    1. Stroke risk reduced 40-50% in women between highest and lowest quintiles of physical activity [9]
    2. Stroke risk is also likely reduced substantially in men
  4. Diet
    1. Recommendation of at least 5 servings of fruits and vegetables per day
    2. Persons with highest quintile of fruits/vegetable intake had a relative risk of
  5. 69 for ischemic stroke compared with lowest quintile [10]
    1. Fiber intake may be correlated with reduced stroke risk
    2. Whole grain comsumption in women associated with reduced ischemic stroke risk [11]
    3. High intake of fish and omega-3 fatty acids associated with 10-50% reduced stroke risk in women [12]
  6. Antiplatelet Agents
    1. Aspirin (ASA, see below)
    2. Clopidogrel - mainly in patients with existing vascular disease or in ASA intolerance
    3. Anticoagulation generally more effective than antiplatelet therapy in AFib patients
  7. Blood Pressure (BP) Normalization
    1. ACE inhibitors (ACE-I) are generally recommended first line
    2. Angiotensin II receptor blockers (ARB) likely as effective as ACE-I
    3. Losartan, an ARB, reduced CV morbidity, stroke and death more than atenolol (a ß-blocker), independent of BP control, in 55-80 year olds [42,43]
    4. Thiazide diuretics (such as hydrocholorothiazide) are added if BP reduction not optimal
    5. Perindopril, an ACE-I, reduced risk of recurrent stroke 28% or any CV event in patients with previous stroke [8]
  8. Weight Reduction
    1. Improves CV status
    2. Improves glucose tolerance
  9. Diabetes Mellitus (DM)
    1. Good control is essential to reducing all vascular complications
    2. Weight reduction and exercise reduce risk and severity of DM
  10. Alcohol Intake [14,39]
    1. Moderate (0.3-2 drinks per day) consumption associated with 20-50% stroke risk reduction
    2. No difference in stroke risk reduction (20%) with 2 drinks versus 6 drinks per week [14]
    3. two to 3 fold increased risk of stroke with >6 drinks per day
    4. Mild to moderate alcohol consumption does not increase risk of hemorrhagic stroke
  11. Homocysteine Reduction
    1. Homocysteine levels correlated with stroke risk and all vascular events
    2. Increased Vitamin B6, B12, folate intake may reduce stroke risk
    3. Increased folate alone associated with 20-30% reduction in stroke risk [15]

D. Cholesterol (Chol) Reduction [1,2,13] navigator

  1. All hyperlipidemic persons should be treated aggressively with statins ± additional chol lowering agents to reduce both stroke and CV risk [13]
  2. Elevated Chol be treated particularly aggressively with statins in stroke patients [13]
    1. Statins (HMG-CoA reductase inhibitors) reduce both initial and recurrent strokes [19]
    2. Statins reduce primary and secondary strokes ~20% (relative risk reduction)
    3. Risk reduction with statins is independent of extent of coronary artery disease (CAD)
  3. Non-statin Chol lowering agents may increase risk of stroke and should be avoided as primary therapy
  4. Specific Statins
    1. Pravastatin (Pravochol®) reduced risk of stroke from 4.5% to 3.7% in patients with CAD [16]
    2. Atorvastatin (Lipitor®) treatment in patients with HTN and average or low Chol levels reduces stroke and CV events ~30% [40]
    3. Simvastatin (Zocor®) reduced non-hemorrhagic strokes by 25% within 2 years [45]

E. Aspirin (ASA) [1,18,36,37] navigator

  1. Overal inconsistent results (range: 10% reduction to 22% increased risk)
  2. ASA had 30% stroke risk reduction in patients after myocardial infarction [1]
  3. Secondary prevention probably does not benefit from increased doses of ASA [20]
    1. Addition of other agents to ASA for secondary prevention is under study
    2. Clopidogrel has increased benefits over ASA for secondary prevention (see below)
    3. Aggrenox® (combined ASA + dipyridamole) moderately more effective than ASA alone [13,21]
    4. In black patients, ticlopidine 500mg/d no more effective than ASA 650mg/d [41]
  4. ASA in Atrial Fibrillation [22,23]
    1. Overall, for patients with atrial fibrillation (AFib), warfarin is the agent of choice
    2. Warfarin INR 2-3 reccommended for AFib with high stroke risk
    3. For patients with low risk AFib, aspirin 325mg/d can be used to reduce stroke risk
    4. Low risk includes non-valvular AFib, no history of stroke, no heart failure, BP<160mm
    5. Low risk also requires left ventricular ejection fraction be >25%
    6. Warfarin may be combined with low dose ASA (81mg/d) for metal valve prophylaxis
    7. AFib with moderate stroke risk should have individualized stroke prophylaxis [23]
    8. Complication rates for ASA are about half the rates for warfarin [24]
  5. Adding dipyridamole (Persantine®) to ASA (combination called Aggrenox®) reduces stroke risk modestly compared with ASA alone [13,21]
  6. Recommend ASA for ALL patients with acute coronary syndromes or myocardial infarction
  7. In high risk patients, particularly with previous stroke or TIA, ASA+dipyridamole recommended

F. Clopidogrel (Plavix®) [25] navigator

  1. Primary prevention of stroke in patients with atherosclerosis
  2. Thienopyridine that irreversibly inhibts platelet aggregation
  3. Binds to ADP receptors (adenyl cyclase coupled) on platelet surface
  4. Clopidogrel is similar to ticlopidine in structure and efficacy without neutropenia
    1. Ticlopidine reduces risks for stroke and all thromboembolic events 25-35%
    2. Side effects of ticlopidine include neutropenia and thrombotic thrombocytopenic purpura
    3. Clopidogrel should ALWAYS replace ticlopidine for any chronic use
  5. Rash and diarrhea are major side effects
  6. Strongly recommended for patients with previous stroke or at very high risk
  7. May be combined safely with ASA 81mg/d with added stroke reduction

G. Warfarin (Coumadin®) navigator

  1. Warfarin is clearly more effective than ASA in preventing cardioembolic strokes
  2. No benefit but increased complications compared with ASA overall for secondary stroke prevention [26]
  3. Strongly Recommended in AFib
    1. Especially in patients with Rheumatic Heart Disease
    2. Risk for stroke in AFib can be determined fairly accurately [27]
    3. Preferred over ASA and other agents for all moderate and high risk patients
    4. For patients with low CV risks and AFib, ASA may be sufficient [22]
    5. INR 2.0-3.0 is more ~2X effective than INR 1.5-2.0 in AFib [44]
    6. In patients with AFib and cerebral ischemia, INR target is ~3 [23]
  4. Strongly recommended for left ventricular (LV) thrombi
  5. Also recommended for reduced LV ejection fraction (heart failure)
  6. For metal heart valves, warfarin can be safely combined with 81mg/d ASA
  7. Consider in patients with patent foramen ovale and atrial septal aneurysm [29]
  8. Complications rates for warfarin about twice that of ASA [24,26]

H. Carotid Endarterectomy and Stenting [1,2,13,30] navigator

  1. Symptomatic Carotid Artery Stenosis (CAS)
    1. Prevents stroke in any symptomatic patient with CAS >70%
    2. Significantly prevents stroke in patients >75 years with CAS >50% [32]
    3. Benefit both in reducing recurrent strokes and lowering functional impairment by ~80%
  2. Asymptomatic Patients
    1. For carotid stenosis <60%, endarterectomy will not improve outcomes
    2. For carotid stenosis >70%, good evidence that endarterectomy prevents strokes
    3. Reduced stroke within 5 years ot operation in asymptomatic patients <75 years with >70% stenosis from 12% to 6% [46]
    4. Caution in recommending endarterectomy to asymptomatic patients
  3. At 3 years, >28% of endarterectomy and 25% of carotid stenting high risk patients had major events showing non-inferiority of stenting [47]
  4. Morbidity / Mortality ~2% in a good center in reported trials
  5. However, risks of proceedure are highly dependent on volumes and surgeon expertise
  6. Elderly patients without other major comorbidities may be offerred endarterectomy [32]

I. Effectiveness of Stroke Prevention [1] navigator

  1. Based on number of patients required to treat (NNT) to prevent 1 primary stroke per year
  2. In patients with atrial fibrillation, warfarin treatment NNT is 13
  3. In patients with high grade carotid stenosis and a TIA, NNT is 6-26 4 Aspirin NNT overall is 200-400 (in patients with myocardial infarction)
  4. Antihypertensive therapy NNT is 8000
  5. ACE inhibitors alone NNT is 11,000
  6. Statins NNT of 13,000 (NNT 50-200 for prevention of 1 myocardial infarction)
  7. For secondary prevention, NNTs are all <100
  8. Likely that current CV prevention reduces stroke risk substantially

References navigator

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