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Advances in Stroke Prevention
Dr. G. Devathasan
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Stroke Subtypes by MRA/MRI/
U-S/Blood screen
A) Hemorrhagic --- small vessel rupture,AVMS, Aneurysms
B) Occlusive or Ischemic. Ask where the
source is (etiology)i) Carotids, arch, vertebrals
ii) Circle of Willis, basilarNote thedifferences in the behavior of the
endothelium at different sitesiii) Small vessel disease --- eventuallydiffuse leading to vascular dementia,Biswangers, amyloid, Cadasil
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iv) Cardiac embolivalvular, AFparoxysmal
v) Vasospasm TMA vs. TIAvi) Mixed leading to diffuseatherosclerosis
vii) Systemic Disordersantibody
syndromes. E.g. APA, abnormal clottingprofile, primary lipid disorders
viii) Venous disorders --- venous relatedinfarcts
ix) Trauma --- dissectionh) Inflammatory or unknown Takayasus,Moya-moya, etc
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Proposed Etiology of Primary
Hypertension
Chronic lack of fluid intake (not salt)Shrinkage of the blood volume
Renin/ angiotensin & other vasopressors
Arteriole spasmArteriole sclerosis
Atherosclerosis, Small vessel disease
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Management
Systolic below 140 & diastole below 85. Take
height & pulse rate into account. Avoidwatershed infarcts by hypotension
Fluids to be taken in generous portion of 3 litersper day in divided portions
Choice of antihypertensives from the ABCDgroupspersonal
ALLHAT study biased towards diuretics from itsdesign & analysis
All BP can be controlled with present range ofdrugs
Treat the labile & the nocturnal rise, especially ifassociated with sleep apnoea
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Powered vulgar word. More patientsimply dubious product. E.g. ALLHAT study
(19,000) 10 % dropout, especially thediuretic group
NNT or Number Needed to Treat --- Goodword & concept. 1/ARR
Double blind study required when aproduct does not speak for itself.Streptomycin, penicillin did not requiresuch studies
Meta-analyses; only successful studiespublished. Negative ones discarded bydrug companies
Statisticians not blinded. E.g. Caprie study
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Invariable influence of drug companies.
Disclaimer statements are insufficient Fabrications of data in reputable journals
not uncommon. Publish or perish pressureof Institutions. Classic example case of
H.S. of Bells Institute published 14fraudulent peered review articles in 18months in Science & Nature
There is still no substitute to astute clinical
experience & observation your feel of adrug
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Antiplatelets
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Meta-analyses
Antiplatelets Trialist collaboration (73,000)
27 % reduction risk composite outcome
Algral & al (10 trials)
16 % reduction composite outcome
Johnson & colleagues (500)
15 % reduction
Aspirin loses its value after 5 years
probably
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Thienopyridines
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Ticlopidine TASS after 1 year noadvantage over aspirin
CATS Ticlopidine vs. Placebo RRR 23 %
Cure trial end point not for strokes
Caprie: Plavix vs. Aspirin; no advantage &
Plavix appears to have no effect forstroke prophylaxis & more for PVD &coronary events
MATCH for combination therapy for TIAs
results pending But ACCP guidelines; Plavix is equal to
Aspirin
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Aspirin & Dipyrimadole
Earlier studies negative:
ESPS2 (Combination vs. Placebo) favorable results
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Warfarin (since 1924)
Bishydroxycoumarin
Rodenticide Clotting factors II, VII, IX, X
SPIRITS INR 3 - 4.5 negative study
WARSS; no advantage over Aspirin Subtypes PFO, cardiac & APA
WASID for intracranial stenosis subtypes
Retrospective study favorable;
prospective study pending ESPIRIT study pending
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Other Preventive Measures
Homocysteine lowering ?, HRA
GP 11b/111a receptor antagonists
trials abandoned
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Lipid Lowering Agents
Cholesterol is not a potent risk factor
Cardiovascular events should not beequated to cerebrovascular events
No substitute for leanness & diet
Small risk of Rhabdomylosis/Polyneuropathy
Higher risk of Hemorrhagic strokeswith cholesterol below 150 mg
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Non statins cholesterol lowering agentshad no impact on stroke outcome
Statins still dubious
E.g. Care study with Pravastatin (4159)
10.2 % vs. 13.2 % ARRR is 3 %
What it means is we need to treat 33
patients for a few years to prevent one
stroke case
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What then is the future?Carotid endarterectomy & stents
are of very limited value
Thrombolyticsrisk of Hemorrhage &Edema high
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Look at Plaque regression & in theCircle of Willis systolic peak velocityreduction
Manipulation of the autonomic(sympathetic) system. Nitric oxide
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