MANAGEMENT AND PREVENTION OF STROKE
From University of California, San Francisco, School of Medicine’s Primary Care Medicine: Principles and Practices
S. Andrew Josephson, MD, Assistant Professor, Department of Neurology, University of California, San Francisco,
School of Medicine
Time-based Therapy
| First question to ask: when was last time patient seen normal (not, when did stroke start?)? when stroke started
during sleep, patient will say it occurred when awakened
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| Time of onset: 0 to 3 hr—intravenous (IV) tissue plasminogen activator (IV-tPA); 0 to 6 hr—intra-arterial (IA) tPA
(IA-tPA); 0 to 8 hr—mechanical embolectomy; >8 hr—anticoagulants or antiplatelet therapy
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| Efficacy of therapy: IV-tPA—proven by multiple studies; approved by Food and Drug Administration (FDA);
found effective and safe, even in less experienced centers; IA-tPA—proven by trials but not approved by FDA; mechanical
embolectomy—Mechanical Embolus Removal in Cerebral Ischemia (MERCI) retrieval system; FDA-approved;
randomized trial data lacking; clinical practice—all widely used in stroke centers
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| Diagnosis and treatment: at speaker’s institution, computed tomography angiography (CTA) used in all suspected
strokes and transient ischemic attacks (TIAs); with CT perfusion, green areas of brain ischemic but not infarcted,
red areas infarcted; opening arterial occlusion can save green areas; CT perfusion possible with same CT scanner
used for spiral CT for pulmonary embolism (PE)
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| Etiology of TIA: atrial fibrillation (AF)-related cardioembolic disease; patent foramen ovale (PFO); carotid artery
dissection; small vessel stroke; endocarditis with related septic emboli; other causes (seizure; migraine)
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Differential Diagnosis of TIA
| Differential diagnosis: vascular cause; seizure; complicated migraine
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| Risk stratification for TIA: ABCD2 score; estimates 7-day risk for stroke after TIA; overall risk ≈10%
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 | Age >60 yr: 1 point
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| Blood pressure (BP): systolic >140 mm Hg or diastolic <90 mm Hg, 1 point
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| Clinical features: unilateral weakness, 2 points; speech disturbance without weakness, 1 point
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| Duration: >60 min, 2 points; 10 to 59 min, 1 point
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| Diabetes: 1 point
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| ABCD2 score and 48-hr risk for stroke: 6 to 7 (8.1%; high risk); 4 to 5 (4.1%; moderate risk); 0 to 3 (1.0%; low risk)
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| Aggressive therapy for TIA: 2 studies from Europe (Lancet 2007; Lancet Neurology 2007); patients with TIA admitted
to clinic and given rapid diagnosis (eg, CTA, echocardiography, and carotid examination), followed by rapid
therapy, eg, for AF, carotid artery pathology; reduced stroke risk (as predicted by ABCD2 score) by ≈80%; “this is
our unstable angina”
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| Approach to stroke treatment
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| Determine whether acute stroke therapy indicated
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| If not, whether patient should be placed on anticoagulants (warfarin with or without bridging heparin)
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| If not, antiplatelet therapy indicated
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| Indications for anticoagulation: AF; some other cardioembolic sources (thrombus in left ventricle; possibly ejection
fraction <35% or PFO with atrial septal aneurysm); vertebral or carotid artery dissection; rare hypercoagulable
states (antiphospholipid antibody syndrome supported by data)
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Carotid Artery Dissection
| TIA vs stroke: magnetic resonance imaging (MRI) shows 50% of patients with TIA have infarction in brain, so not
useful to think of TIA and stroke as different entities; only difference that in TIA, area has enough collateral vessels
or area not eloquent enough to produce symptoms; on MRI, crescent sign (hemosiderin) on wall of internal carotid
artery diagnostic for dissection
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| Cervical artery dissection: vertebral or carotid arteries; rare cause of stroke in older patients but common etiology
in patients <50 yr of age; pathophysiology—tear in blood vessel wall exposes endothelium, leading to clot formation;
mechanisms of stroke (clot serves as embolic source, leading to artery-to-artery embolism; clot increases in
size and occludes vessel); risk factors—idiopathic; severe vomiting or coughing; chiropractic neck manipulation
(for vertebral artery dissection, especially in young women); presentation—focal neurologic deficits accompanied
by neck pain; treatment—anticoagulation (usually 3-6 mo), followed by lifelong antiplatelet therapy
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| Standard work-up for large-vessel stroke
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| Cardioembolic: AF; blood clot in heart; paradoxical embolus; study—telemetry; echocardiography with bubble
study (looking for right-to-left shunt)
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| Aortic arch: atherosclerosis with artery-to-artery emboli; studies—transesophageal echocardiography (TEE); vascular
imaging of chest
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| Carotids: studies—ultrasonography (US); CTA; magnetic resonance angiography (MRA); conventional angiography
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| Intracranial vessels: atherosclerosis in middle cerebral artery causing artery-to-artery embolus; studies—MRA;
CTA; conventional angiography
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| Evaluate and treat stroke risk factors
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Cardiac Issues
| Comparison of studies for stroke: 231 consecutive patients with TIA or stroke underwent transthoracic echocardiography
(TTE) and TEE; 127 had cardiac cause of emboli (90 [70%] seen only on TEE); 46 patients had major
risk factors (mostly thrombus on left atrial appendage) requiring anticoagulation (in 38, detected only on TEE);
TEE superior to TTE for examining left atrial appendage, right-to-left shunts, and aortic arch
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| Protocol for ordering TEE: adopted by speaker’s institution for stroke patients without reason for anticoagulation
and no contraindication to anticoagulation (not evidence-based)
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| Age <55 yr: order TEE
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| Age >55 yr: perform surface echocardiography; if results show any of abnormalities below, order TEE
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| Normal ventricular systolic function without left ventricular hypertrophy
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| No prosthetic valve
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| No valvular stenosis and no more than mid-mitral or aortic regurgitation
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| Left atrium dimension <10 mm
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| No visualized valvular regurgitation or intra-aortic masses
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| Detecting AF: electrocardiography (ECG) and telemetry for 48 hr, 24 hr of telemetry, or telemetry in emergency
department for 0.5 hr not adequate to capture all patients with paroxysmal AF; study—30-day event monitor found
20% of patients had AF (most detected between days 7 and 30)
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Antiplatelet Drugs
| Antiplatelet options: aspirin—50 mg to 1.5 g equally effective in stroke; dipyridamole plus aspirin (Aggrenox)—
25 mg aspirin plus 200 mg extended-release dipyridamole; taken bid; effective and more beneficial than aspirin
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| Clopidogrel (Plavix): more effective than aspirin; clopidogrel-aspirin combination not recommended (except for
cardiac reason); Aggrenox-clopidogrel combination no longer used
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| Aggrenox vs clopidogrel: Aggrenox—in trial, 30% of patients discontinued drug because of severe headache in
first 2 wk; perhaps not compatible with cardiac antiplatelet goals or unstable angina; in dysphagia, cannot be
crushed and placed in feeding tube; clopidogrel—less direct evidence from stroke trials; concerns about combining
with aspirin; awaiting results of trial comparing Aggrenox to clopidogrel in stroke patients
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| Antiplatelet options: no antiplatelet medication at time of stroke or TIA—aspirin for 1 to 2 wk; switch to Aggrenox
or clopidogrel (Aggrenox treatment of choice in guidelines; if not tolerated, clopidogrel); already on aspirin—
switch to Aggrenox or clopidogrel (Aggrenox never tested in first 2-3 days after stroke)
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| Additional management of acute stroke: statin for almost everyone; permissive hypertension (mistake to lower
BP during stroke or TIA; allowing BP to remain ≤220/120 mm Hg prevents increased areas of infarction and improves
mortality; begin lowering BP after 3 to 7 days); tight glucose and fever control; enoxaparin for prophylaxis
of deep venous thrombosis (DVT)
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| When to fix carotid: endarterectomy for symptoms in patient with 70% to 99% stenosis ipsilateral to stroke or
TIA; little benefit in 50% to 69% stenosis, especially in women; in stroke management, do not miss carotid stenosis
or AF (best evidence for secondary prevention)
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| Endarterectomy
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| Stenting: procedure widely adopted; encouraged by 2004 trial demonstrating benefits equivalent to endarterectomy
in very high-risk patients; complications include hypotension and bradycardia; randomized trial results now
available—stenting found inferior to endarterectomy
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| Speaker’s current approach: revascularize patients with lesions >70%; use endarterectomy, except in very high-risk
group (>80 yr of age; simultaneous myocardial infarction; severe congestive heart failure); select surgeons with
most experience
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| Primary prevention guidelines: appeared in 2006 in Circulation
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| Risk estimation schemes: aspirin effective only in high-risk men and medium-risk women (parallels cardiac guidelines);
treat vascular risk factors; anticoagulation for AF (calculate risk using CHADS2 score)
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| Congestive heart failure, 1 point
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| Hypertension, 1 point
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| Age >70 yr, 1 point
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| Diabetes, 1 point
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| S (prior TIA or stroke), 2 points
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| 1 to 2: medium risk
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| ≥3: high risk
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| Endarterectomy in asymptomatic carotid stenosis
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| Some benefit for endarterectomy in asymptomatic stenosis (>80% cutoff)
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| Must have very low perioperative risk for stroke or death (≤3%) for benefit
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| Risk based on both patient and surgeon
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| Benefit not realized for 5 yr
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| Data much less convincing than in trials with symptomatic patients
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| Whom to screen: very few patients; unknown what to do with results; stenting carries risk for rethrombosis; avoid
screening for carotid stenosis as much as possible
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| Folic acid supplementation: does not work for prevention of MI or dementia; meta-analysis of 8 randomized
trials—found stroke risk reduced 18%; greatest effects seen with >36 mo of supplementaton and when patients’ homocysteine
reduced >20%; most trials in Europe (without fortification of grain); folic acid most helpful in primary
prevention
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Questions and Answers
| Periventricular white matter: what to do when detected by CT or MRI in patient who fell and hit head; also
called small vessel disease and subcortical ischemic vascular disease; treatment uncertain; may not be strokes;
while associated with dementia and vascular risk factors, effect of therapy unknown; speaker treats as stroke-equivalent
(antiplatelet therapy; but not full stroke work-up)
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| Treatment of acute stroke: IV-tPA—beneficial within first 3 hr (confers 30% greater chance of being functionally
normal in 90 days); increases hemorrhagic conversion risk from 1% to ≈6%; IA-tPA—beneficial within first 6 hr; otherwise,
same as IV-tPA; MERCI retrieval system—removing clot seems to double benefit in patients with large-vessel
proximal occlusion with little hemorrhage; FDA approved without randomized trial (protocol for devices)
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| Stroke management in community: only 30% to 50% of patients seen within 8 hr; hub-and-spoke model expected
to develop (patients needing more sophisticated intervention diverted to hospitals with capability)
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| Screening elderly patients: screening for bruit not particularly helpful (usually absent in stenosis >90% or <50%;
identifies moderate stenosis); order screening examination when cause for concern
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| Increasing public awareness: need to educate patients to come to hospital quickly and doctors to manage stroke
aggressively
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| Cost-effectiveness: Aggrenox trial found ≈30% reduction in stroke over 5 to 10 yr (“pretty minimal for year”); clopidogrel
probably similar; patients often unable to afford Aggrenox or clopidogrel; aspirin “great medicine for secondary
prevention”
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| tPA and risk for hemorrhage: imaging techniques used to evaluate perfusion; small area of infarction but large
area of ischemia warrants aggressive therapy, regardless of time since stroke; conversely, patient with large infarction
but no salvageable tissue unlikely to benefit from tPA; symptoms unhelpful (could be from ischemic areas or
infarcted areas); dramatic symptoms not basis for withholding tPA in patients presenting within 3 hr
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| Carotid US overused: undiagnostic in patients presenting with dizziness; anterior circulation does not feed any
structures that cause dizziness (vertebral and basilar arteries involved in dizziness); if carotid pathology found, it is
asymptomatic disease unrelated to dizziness
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Suggested Reading
Amarenco P et al: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 355:549, 2006;
Bath P: Role of aspirin in MATCH. Lancet 364:1662; author reply 1662, 2004; Diener HC et al: Aspirin and clopidogrel
compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients
(MATCH): randomised, double-blind, placebo-controlled trial. Lancet 364:331, 2004; Durga J et al: Effect of
3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind,
controlled trial. Lancet 369:208, 2007; Goldstein LB et al: Primary prevention of ischemic stroke: a guideline from
the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic
Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology
Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary
Working Group. Circulation 113:e873, 2006; Erratum in: Circulation. 2006; Johnston SC et al: Validation
and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 369:283,
2007; Lavallée PC et al: A transient ischaemic attack clinic with round-the-clock access (SOS-TIA): feasibility
and effects. Lancet Neurol 6:953, 2007; Rothwell PM et al: Effect of urgent treatment of transient ischaemic attack
and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison.
Lancet 370:1432, 2007; Rothwell PM: Lessons from MATCH for future randomised trials in secondary prevention
of stroke. Lancet 364:305, 2004; Sciolla R et al: Rapid identification of high-risk transient ischemic attacks: prospective
validation of the ABCD score. Stroke 39:297, 2008; Sherman DG et al: The efficacy and safety of enoxaparin
versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke
(PREVAIL Study): an open-label randomised comparison. Lancet 369:1347, 2007; SPACE Collaborative Group
et al: 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic
patients: a randomised non-inferiority trial. Lancet 368:1239, 2006; von Maxen A et al: ESPRIT trial. Lancet
368:448, 2006; Wang X et al: Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet
369:1876, 2007.
Educational Objectives
| The goal of this program is to improve management and prevention of stroke. After hearing and assimilating this program,
the clinician will be better able to:
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| 1. Implement time-based therapy in managing stroke.
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| 2. Perform differential diagnosis of transient ischemic attack (TIA).
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| 3. Diagnose carotid artery dissection.
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| 4. Order transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) studies for stroke
and TIA.
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| 5. Prescribe antiplatelet agents, including dipyridamole plus aspirin (Aggrenox), clopidogrel, and aspirin.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning
committee reported nothing to disclose.
Acknowledgements
Dr. Josephson was recorded at Primary Care Medicine: Principles and Practices, sponsored by the University of California,
San Francisco, School of Medicine, October 25-27, 2007, in San Francisco. The Audio-Digest Foundation
thanks Dr. Josephson and UCSF School of Medicine for their cooperation in the production of this program.
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