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CVA OVERVIEWCVA OVERVIEW
Ron Barac, DOInternal Medicine Lecture SeriesMillcreek Community Hospital
April 16, 2008
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Emergency Evaluation of Strokefirst 15 minutes
ABCs Document Hx & PE – Especially time last known to be normal – NOT when symptoms first noted…. Blood work (CBC, CMP, INR/PT/PTT) EKG, CXR Send for brain imaging Consult Neurology
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Stroke in the U.S.Stroke in the U.S.
750,000 new strokes annually Mortality rate 20-25% Leading cause of long term disability in
adults Economic impact - $40 billion in health
care costs and lost productivity Personal impact - patient and family
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Stroke SubtypesStroke Subtypes
S troke
Large A rteryA therosc leros is
S m all V esselD isease
(lacunar in farc tion)
C ard ioem bolism O ther
Ischem ic S troke - 80% H em orrhagic S troke - 20% Intracerebral hem orrhage Subarachnoid hem orrage
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TIATIA
A stroke-like deficit that resolves in under 24 hrs
80% resolve within 60 minutes– Median duration is 14 minutes
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Event Risk Within 3 MonthsEvent Risk Within 3 MonthsAfter TIAAfter TIA
Johnston SC, et al. JAMA. 2000;284:2901 2906.
RecurrentTIA
Cardiac Event
Stroke Death
Eve
nt R
ate
12.7%
2.6% 2.6%
10.5%
5% in 48 hrs
• age > 60 years
• diabetes mellitus
• duration of episode greater than 10 min
• weakness and speech impairment with the episode
Independent risk factors for stroke within 90 days after TIA:
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Non-Modifiable Risk FactorsNon-Modifiable Risk Factors
Age Race ( African-American, Hispanic ) Sex ( male > female ) Family history, genetic components
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Primary PreventionPrimary Prevention
HTN (both systolic and diastolic and isolated systolic)
Atrial Fibrillation– warfarin
INR goal 2.0 - 3.0 reduces ischemic events by approx. 65%
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Primary PreventionPrimary Prevention
Atrial Fibrillation– aspirin
for “low risk” patients reduces ischemic events by approx. 20% low dose warfarin plus aspirin not as effective as
adjusted dose warfarin
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Primary PreventionPrimary Prevention
Other Cardiac Conditions– valvular disease– post-MI survivors– HF, LVH, etc.
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Primary PreventionPrimary Prevention
Diabetes Mellitus Hyperlipidemia
– Statins prevent stroke in DM regardless of the presence of vascular dz. (even with normal cholesterol)
– Statins recommended for primary prevention in patients with CAD; goal <70 in very high risk patients
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Primary PreventionPrimary Prevention
Carotid Artery Disease (asymptomatic)– consider CEA for stenoses > 60%
Carotid Angioplasty and Stenting– should be reserved for high risk patients failing
best medical management; should only be done by rigorously qualified providers
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Primary PreventionPrimary Prevention
Smoking Cessation Alcohol Intake
– mild / moderate intake may be beneficial– excessive intake detrimental
Exercise and weight loss OCP’s + Smoking
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Primary PreventionPrimary Prevention
Treatment of sleep-related breathing disorders
Cessation of cocaine use Dietary changes (Mediterranean diet) ACE inhibitors ( HOPE trial ) Angiotensin receptor blockers Treatment of metabolic syndrome
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Secondary PreventionSecondary Prevention
Aspirin– optimal dose – ( 50 to 325 mg ) no clear
evidence that high or moderate dose is better than low dose
– only antiplatelet agent proven in acute setting (for stroke); give within 48 hours
– approximately 22 % risk reduction
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Secondary PreventionSecondary Prevention
Aggrenox (ASA 25 mg + extended-release dipyridamole 200mg)– superior to ASA alone ( 37% risk reduction c/w
placebo, 23 % c/w ASA)– 7th ACCP conference recommends it (or Plavix)
be used first-line instead of ASA for non-cardio embolic stroke or TIA
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Time in Months
ESPS 2: Primary Outcome
Reprinted from the Journal of the Neurological Sciences, Vol 151 (suppl), ESPS 2 Group, European Stroke Prevention Study 2, Efficacy and safety data, S1-S77, 1997, with permission from Elsevier. .
Survival Curves for Fatal and Nonfatal Stroke
0 6 12 18 24
Su
rviv
al P
rob
abil
ity
0.750
0.800
0.850
0.900
0.950
1.000
Placebo
ASA
ER-DP
ASA/ER-DP
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ESPS 2: SummaryESPS 2: Summary
• ASA/ER DP is about twice as effective as aspirin alone in secondary stroke prevention1
• There was a 20% relative risk reduction in the secondary endpoint stroke/MI/ vascular death with ASA/ER DP vs. aspirin2
• Bleeding rate of the combination of ASA/ER DP is comparable to aspirin alone1
• In a post hoc analysis, no increase in cardiac events was reported with ASA/ER DP3
1. ESPS 2 Group. J Neurol Sci. 1997;151(suppl):S1 S77.2. Data on file, Boehringer Ingelheim Pharmaceuticals, Inc. 3. Diener HC, et al. Int J Clin Pract. 2001;55:162 163.
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Secondary PreventionSecondary Prevention
Plavix (Clopidogrel) Reduces combined risk of stroke, MI and
vascular death in patients with atherosclerotic vascular disease– relative risk reduction vs. ASA - 8.7%– stroke + death rate may be same as ASA– less side effects vs. ticlopidine
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Secondary PreventionSecondary Prevention
Plavix plus ASA (MATCH trial)– benefit of combination over Plavix alone
cancelled out by excess bleeding present– validity of results questioned due to the paucity
of large artery atherosclerosis represented
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CAPRIE and MATCH: SummaryCAPRIE and MATCH: SummaryCAPRIE 1 MATCH 2
Comparator Clopidogrel vs. aspirin Clopidogrel + aspirin vs. clopidogrel
Patients 1/3 stroke, 1/3 MI, 1/3 PAD 79% stroke, 21% TIA
Primary outcome
Vascular death, non fatal MI, or stroke
Ischemic stroke, MI, vascular death, or re-hospitalization
Result The combined patient population showed a slight but significant benefit of clopidogrel over aspirin.
Individual patient group analysis showed no significant benefit of clopidogrel over aspirin in MI or stroke patients.
There was no significant difference in efficacy of combination therapy (clopidogrel + aspirin) compared with clopidogrel alone.
Significant increase in life- threatening and major bleeding in combination clopidogrel + aspirin therapy compared with clopidogrel alone.
1. CAPRIE Steering Committee. Lancet. 1996;348:1329 1339. 2. MATCH trial. Lancet. 2004;364:331 337.
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Secondary PreventionSecondary Prevention
Ticlopidine (Ticlid)– relative risk reduction vs. ASA - 10%– possibly greater benefit in women, patients with
completed stroke or vertebrobasilar ischemia– 2% incidence of neutropenia
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Secondary PreventionSecondary Prevention
Warfarin (Coumadin)– atrial fibrillation– post-MI ventricular thrombus– valvular disease– ? antiplatelet treatment failure ( benefit over
ASA not apparent in noncardioembolic disease- WARS study)
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Secondary PreventionSecondary Prevention
ACE inhibitors + diuretics ( PROGRESS trial )– Perindopril ( Aceon ) + indapamide ( Lozol )-
47 % risk reduction PRoFESS trial
– comparing Aggrenox vs Plavix– ongoing
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Secondary PreventionSecondary Prevention
Carotid Endarterectomy ( for symptomatic stenosis )– CEA for men with stenosis > 50% and women
with stenosis > 70% if 30 day operative morbidity / mortality < 6%
– Benefit lost with significant delay to surgery
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Secondary PreventionSecondary Prevention
Angioplasty and Stenting– CREST trial-carotid stent=CEA for high risk
symptomatic patients >70%– use for symptomatic intracranial disease should
be evaluated on a case by case basis, and should be performed by rigorously qualified providers
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Acute Stroke ManagementAcute Stroke Management
Stroke Alert ( TIME IS BRAIN ! ) Acute Diagnosis
– clinical level of consciousness location of stroke severity of stroke - NIH stroke scale
ABC’s
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Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization
Left MCA-aphasia, R hemiparesis ( face & arm > leg ), +/- visual field defect, gaze palsy, sensory loss
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Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization
Right MCA-L hemiparesis, +/- visual field defect, gaze palsy, sensory loss
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Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization
PCA-contralateral visual loss, confusion, +/- aphasia
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Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization
ACA-contralateral leg weakness and numbness, incontinence
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Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization
PICA-ipsilateral facial & contralateral body sensory loss, dysarthria, ataxia, vertigo, ipsilateral Horner syndrome
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Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization
VB-some combination of ataxia, vertigo, N/V, weakness, diplopia, dysarthria, coma
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Acute Stroke ManagementAcute Stroke Management
Acute Diagnosis– clinical
remember differential diagnosis - trauma, CNS infection, seizure, hypertensive encephalopathy, mass lesion, migraine, metabolic, toxic
– radiologic noncontrast CT MRI/MRA ( diffusion/perfusion ) CT angiography
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Acute Stroke ManagementAcute Stroke Management
Acute Medical Assessment – cardiac dysrhythmias ( EKG )– peripheral vascular assessment– r/o trauma in comatose patients– r/o metabolic problems and overdose– r/o hypoxemia, anemia, CHF
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General– positioning - head of bed flat or nearly flat– ? supplemental oxygen
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General– fluid management
1/3 of stroke patients dehydrated glucose-containing solutions worsen ischemic
damage normal saline - fluid of choice; consider bolus 10-
15cc/kg consider colloid administration (albumin) less aggressive fluid resuscitation after first 24 hours
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General– NPO– aggressive treatment of hyperthermia– treatment of hyper/hypoglycemia– aspiration precautions– DVT prophylaxis
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General– GI prophylaxis– aggressive treatment of seizures– thiamine if EtOH or malnourished– ASA– ? heparin - unproven
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General – blood pressure management
thrombolytic candidates: BP < 185/110 non-thrombolytic candidates:
– BP < 220/120; MABP < 130
– treat if aortic dissection, MI, CHF, hypertensive encephalopathy
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General– blood pressure management
drugs of choice– nitropaste - 1 to 2 inches
– labetolol - 10 to 20 mg IV (drip 2 - 8 mg/min.)
– enalapril - 1.25 mg IV
– nicardipine – 5 to 15 mg IV/hour
– nitroprusside (if severe) - 0.5 ug/kg/min. IV
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General– blood pressure management
hemorrhagic stroke - ? more aggressive management
– frequent neuro checks and vitals - emergent CT if neuro change
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Acute Stroke ManagementAcute Stroke Management
Acute Treatment - General– cardiac monitoring – treat anemia, hyponatremia, hypomagnesemia
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Acute Stroke ManagementAcute Stroke Management
Subsequent Treatment– mobilize after 24 hours ( if neuro stable )– early PT / OT / speech therapy / stroke ed.– aspiration precautions– strict I’s and O’s
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Acute Stroke ManagementAcute Stroke Management Subsequent Treatment
– prevention / treatment of cerebral edema oncodiuretic therapy ( albumin + lasix ) elevate head of bed avoid fever, hyponatremia, seizures, hyperglycemia,
hypotonic IVF hyperventilation - pCO2 25 to 30 mannitol (0.5 to 2 g / kg IV) glycerol 250 cc of 10% solution q 6 hrs. administration of hypertonic saline ICP - monitoring; barbiturate anesthesia hemicraniectomy and durectomy
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Evaluation (Risk Stratification)Evaluation (Risk Stratification)
Precise anatomic and etiopathogenic assessment helps define prognosis and tailor secondary prevention
Imaging of brain parenchyma– non-contrast CT– MRI ( diffusion-weighted imaging, etc. )
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Evaluation (Risk Stratification)Evaluation (Risk Stratification)
Intracranial vascular assessment– MRA– CT angiography
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Evaluation (Risk Stratification)Evaluation (Risk Stratification)
Extracranial vascular assessment– color Doppler and B-mode ultrasound– MRA– CT angiography
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Evaluation (Risk Stratification)Evaluation (Risk Stratification)
Cardiac assessment– TEE (aortic arch, atria, valves, ventricles)– TTE - may be of little value unless abnormal– EKG and cardiac exam
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Evaluation (Risk Stratification)Evaluation (Risk Stratification)
Serologic assessment– lipid profile– ESR, CBC, PT, PTT– hypercoagulability work-up: protein C, protein
S, lupus anticoagulant, anticardiolipin antibody, anti-thrombin III, Factor V Leiden, homocysteine, ? fibrinogen, ? prothrombin gene mutation, ANA
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Evaluation (Risk Stratification)Evaluation (Risk Stratification)
Serologic assessment– sickle cell screen– consider paraprotein search or neoplastic
search– consider illicit drugs
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Urgent InterventionUrgent Intervention
Reperfusion Neuroprotection
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Urgent Intervention - Urgent Intervention - ReperfusionReperfusion
Aspirin Intravenous t-PA Intra-arterial Prourokinase Ancrod Other (non-pharmacologic) interventions
- supportive care
- carotid endarterectomy ( for TIA )
- angioplasty/stent
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AspirinAspirin
Decreases mortality when given within the first 6 hours (MAST-I)
May improve stroke outcome w/o significant risk of hemorrhage
May have some utility as hyperacute therapy in the field
Recommended to be given within 48 hours
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t-PA (NINDS, NEJM Dec, 1995)t-PA (NINDS, NEJM Dec, 1995)
Placebo controlled, multi-center Treatment within 3 hours of onset Dose: 0.9mg/kg Part 1 (291 patients); Part 2 (333 patients) Patients receiving t-PA 30% more likely to have
minimal or no disability at 3 months Symptomatic ICH in 6.4% (0.6% placebo) Serious systemic hemorrhage in 1.6% (0% placebo) Minor external bleeding in 23% (3% placebo)
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t-PA (Update)t-PA (Update)
Age >80 no longer excluded No benefit beyond 3 hour window(ECASS, ATLANTIS) Trend toward better outcome with
earlier treatment Up to 20% of patients may be
candidates with aggressive approach
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ANCROD ANCROD Venom of the Malaysian pit viper Indirect acceleration of endogenous fibrinolysis 3 hour window, 3 day infusion, 500 patients Requires fibrinogen monitoring (40-70) Positive benefit at 90 days Symptomatic ICH in 5.2% ( 2% placebo ) FDA approval pending
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ProurokinaseProurokinase
Intra-arterial administration in patients with MCA occlusion
6 hour window, 3 hour infusion followed by 4 hour infusion of low-dose heparin
180 patients Positive benefit at 90 days (67% with recanalization) Increased rate of symptomatic ICH but no increase in
mortality FDA approval pending
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HeparinHeparin
No large-scale clinical trials have demonstrated efficacy for routine use of intravenous heparin in acute stroke
Some benefit with subcutaneous heparin, possibly based on DVT prophylaxis
Still advocated in selected patients for prevention of recurrent ischemic events
Other uses are still controversial
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Urgent Intervention - Urgent Intervention - ReperfusionReperfusion
TIME IS BRAIN Strict adherence to protocol to minimize
risk Patient and family should be informed of
potential risks
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t-PA Stroke Protocol - t-PA Stroke Protocol - Inclusion CriteriaInclusion Criteria
Age over 18 Clearly defined time of onset within 3 hours
of treatment Measurable neurological deficit
(NIHSS >4)
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t-PA Stroke Protocol - t-PA Stroke Protocol - Exclusion CriteriaExclusion Criteria
Rapid neurological improvement History suggesting SAH SBP >185 or DBP >110 (can have single dose of anti-
hypertensive tx) Increased ptt, PT>14, platelet count <100K Pregnant or lactating female Acute MI or post-MI pericarditis Glucose <50 or >400 Heme + stool CT exclusion (hemorrhage, ? early ischemic change)
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t-PA Stroke Protocol - t-PA Stroke Protocol - Exclusion CriteriaExclusion Criteria
Prior stroke or serious head trauma within 3 months Major surgery within 14 days Arterial puncture at noncompressable site or lumbar puncture
within 7 days History of intracranial hemorrhage History of brain tumor, AVM, or aneurysm GI or UT bleeding within 21 days Seizure at stroke onset Warfarin treatment Heparin within 48 hours
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t-PA Stroke Protocol - t-PA Stroke Protocol - TreatmentTreatment
t-PA at 0.9mg/kg ( max 90 mg )
- 10% bolus
- 90% as continuous infusion over 60 min No anti-coagulant or anti-platelet agents for 24
hours after treatment ( repeat CT ) BP maintained SBP<180 and DBP<105 Patients must be monitored closely for
neurological deterioration