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88 Cards in this Set

  • Front
  • Back
types of stroke
Ischemic (thromboembolic):
Represents ~ 70-90% of all strokes
Intracerebral hemorrhage:
Represents ~ 10-20% of all strokes
Subarachnoid hemorrhage:
Represents ~ 2-10% of all strokes
the most common type of stroke
ischemic

recovery is the best as well
basic managment of strokes
ABCs.
Complications:
Seizures (prophylaxis for 1-2 weeks with phenytoin).
Hydrocephalus / cerebral edema.
Monitoring:
Blood pressure, intracranial pressure, neuro evaluation, etc.
Signs and Symptoms of Ischemic/Hemorrhage scoring scale
a scale 0-4

0 being good
4 being bad

total score of 25-30 patient is not doing well at all
Modified Rankin Scale for strokes
(best score = 0):
Score of 5-6 = death or severe disability (incontinent or bed bound).
Score of 4 = moderate disability (unable to walk without assistance).
Extended Glasgow Outcome Score for stroke
(best score = 8):
Score of 1-4 = death or unable to care for oneself at home.
Barthel Index for stroke
Score of 100 = complete independence.
Outcomes of Ischemic/Hemorrhage
CT scan may be predictive of outcome and distinguishes ischemia from hemorrhage.
Most improvement in first 90 days.

anyone with altered mental statis gets a CT scan (repeat in 24 hours then 90 days)

improvement can be seen in the CT and correlates with better outcomes
Ischemic Strokes
Most devastating if large arteries are involved (internal carotid artery, basilar artery, anterior cerebral artery).

if blood flow is blocked in the central arteries it results in worse outcomes than if peripheral arteries are blocked
Brain thromboemboli from arterial atherosclerosis:
(ischemic stroke)
~ 20% from cardiogenic emboli, most commonly from atrial fibrillation, ~ 20% from atherosclerotic cerebrovascular disease, ~ 25% are penetrating artery disease, ~ 30% are cryptogenic.
Ischemic Stroke Pathophysiology stages 1-3
Benign Oligemia: Cerebral blood flow is impeded but counterbalanced by prolonged mean transit time of blood from collaterals resulting in normal cerebral blood volume. Metabolic requirements of the brain are still met.
Penumbra: Continued reductions of cerebral blood flow and unmet metabolic requirements (tissue oxygen extraction is maximized) impede synaptic function to cause neurologic deficit. Reversible if blood flow is restored. Over time, ion pumps fail leading to widespread tissue depolarization and release of excitatory neurotransmitters. Accumulation of fatty acids and inflammatory mediators. Water and electrolytes flow into cells.
Core: Tissue energy requirements sore and are unmet. Intravascular clotting further reduces cerebral blood volume. Recanalization of the occluded blood vessel no longer enhances distal blood flow (no-reflow phenomenon). Entering blood can leak out of damaged vessel to cause hemorrhage.
at what stages are strokes irreversible
stage 3
Ischemic Stroke Risk Factors
Modifiable:
High blood pressure.
Diabetes.
Coronary artery disease.
Atrial fibrillation.
Hyperlipidemia.
Smoking.
Moderate alcohol consumption.
Obesity.
Previous transient ischemic attacks.
Hypercoagulable states.
Oral contraceptive use or postmenopausal hormone replacement.
Non-modifiable:
Age > 50 years old.
Male.
African American, Hispanic, Pacific Islanders.
Family history.
Low birth weight.
Therapy of Ischemic Stroke
Tissue-plasminogen activator (t-PA) 0.9 mg/kg iv (10% of dose as bolus and remainder over one hour) with maximum dose of 90 mg:
Grade 1A recommendation if started within 3 hours of symptoms.
Grade 2A recommendation if started 3 – 4.5 hours after onset of symptoms.
Grade 1A recommendation against use if > 4.5 hours after onset of symptoms.
Studies show reduced combined outcome of death or dependence but increased hemorrhage with no mortality benefit.
is tissue plasminogen activator effective in ischemic stroke after 4 hours
there are no longer any benefits
what is the risk of using t-PA
hemorrhage

it does not matter when it is administered there is a 6% chance
Exclusion Criteria for t-PA:(know!!!)
Intracranial or subarachnoid hemorrhage.
Minor or rapidly improving stroke symptoms.
Active internal bleed (or within 21 days).
Coagulopathy (Plts < 100,000/mm3, INR > 1.5).
Head trauma or previous stroke within 3 months.
Trauma or major surgery within 2 weeks.
Lumbar puncture within 7 days.
History of ICH, aneurysm, AV malformation.
Witnessed seizure with stroke onset.
Recent acute MI.
SBP > 185 mmHg or DBP > 110 mmHg at treatment.
Symptoms > 4.5 hours.
Cost ~ $600/patient but cost-effective.
Other Modes of Reperfusion Therapy for ischemic stroke (know)
Intra-arterial thrombolysis:
t-PA has not been investigated for this but other thrombolytics improve 3-month functional outcome (40% vs. 25% with modified Rankin score ≤ 2, p<0.05) but increased intracranial hemorrhage (15.4% vs. 7.1%, p=0.063).
Administer within 6-24 hours of onset (time window depends on location of occlusion).
Medical thrombolysis:
Mechanical Embolus Removal in Cerebral Ischemia (MERCI).
When used with t-PA, trends toward better recanalization, lower mortality, and higher favorable outcomes but small studies.
Other anticoagulation:
If not eligible for t-PA, ASA 160-325 mg/day started within 48 hours of onset and continued for months reduces stroke reoccurrence by absolute reduction rates of 0.6-1.1% (p<0.05) and trend toward reduced mortality (Grade 1A).
If eligible for t-PA, start anti-platelet agents within 24 hours (see next hour of lecture).
if a patient is not eligable for t-PA what can be given to them for an ischemic stroke
ASA with in 48 hours
Intracerebral Hemorrhage (ICH)`
While less frequent, mortality (~33% @ 3 months) and morbidity much higher with ICH than ischemic stroke.
Pathophysiology: Likely related to vascular malformations but other contributing factors include trauma, neoplasms, vasculitis, etc. Three stages (24 hrs): hematoma formation, hematoma enlargement, edema. Clot and vascular injury activates inflammation and leads to edema.
Risk factors: age, male, hypertension, heavy alcohol consumption, current smoking, diabetes, African American or Asian, coagulopathy.
Therapy of ICH
ICH accounts for 10-20% of all strokes, and anticoagulant-associated ICH accounts for ~ 20% of all ICH. (warfarin contributes to 1/5)

Hematoma expansion is an independent risk factor for poor outcomes and high mortality. (trying to reduce the expansion of the bleed)

Anticoagulant (warfarin) use is a risk factor for hematoma expansion and almost doubles ICH mortality.

Rapid INR reversal decreases the risk of hematoma growth and may decrease time to emergent surgery.
the process of clot formation
INITIATION: Tissue Factor/FVIIa interaction leads to thrombin generation
AMPLIFICATION/ PROPAGATION: rFVIIa activates factor X on the surface of activated platelets, leading to an enhanced thrombin burst at the site of injury
FIBRIN CLOT FORMATION: Thrombin converts fibrinogen into fibrin, producing a stable clot
what happens when a patient is given factor VII
it by passes tissue factor and then you get a big thrombin burst
when tissue is injured what is released
tissue factor is released and it activates a small amount of activated thrombin
Therapy of Spontaneous ICH: Factor VIIa (rFVIIa)
INITIATION: Tissue Factor/FVIIa interaction leads to thrombin generation
AMPLIFICATION/ PROPAGATION: rFVIIa activates factor X on the surface of activated platelets, leading to an enhanced thrombin burst at the site of injury
FIBRIN CLOT FORMATION: Thrombin converts fibrinogen into fibrin, producing a stable clot
the controversy of factor VII
Phase IIb Study:

Placebo, rFVIIa: 40, 80 and 160 mcg/kg in 399 spontaneous ICH patients
Dose given within 4 hours of symptom onset
Excluded patients with thrombotic or vaso-occlusive disease
Primary endpoint % change in ICH volume

Outcomes:
Significantly reduced hematoma growth in a dose-dependent fashion

Significantly reduced mortality and significantly improved global functional outcome (mRS and Barthel Index) at 90 days

Was associated with a small increase in the risk of acute thromboembolic events (7% vs. 2%, arterial 5% vs. 0%, p=0.01)
(decrease in mortality and decrease in expansion of the bleed, increase in functional outcomes)
Phase III Study (FAST):

Placebo, rFVIIa 20 mcg/kg and rFVIIa 80 mcg/kg in 841 spontaneous ICH patients
Dose given within 4 hours of symptom onset
Included patients with vascular risk factors
Primary endpoint mRS at 3 months

Outcomes
Reduced hematoma growth (p=0.001)
No improvement in survival or functional outcome after ICH
More ADRs in higher rFVIIa dose group vs. placebo (9% vs. 4%, p=0.04)

Study limitations
Confounding factors may have limited the treatment effect

Target population for rFVIIa administration
Age <70 yr
Time to dose <3 hours
Baseline volume of ICH <60 mL
Baseline intraventricular hemorrhage volume <5 mL
(no improvement of functional outcomes, but they were older patients with bigger bleeds)
Therapy Options for Warfarin-Associated ICH
Vitamin K (doesn't work quickly)
Promotes liver synthesis of clotting factors: II, VII, IX, X.
Used when INR ≥ 1.5 as 0.5 – 10 mg iv, po, SC but slow infusion and slow acting.

Fresh frozen plasma (FFP)
Coagulation factors and fibrinogen in variable amounts.
Used when INR ≥ 1.5 as 15 mL/kg but requires thawing, may cause hypervolemia, and increases infection risk.

Prothrombin complex concentrate (PCC)
Factors II, VII, IX, and X and prothrombin, proteins C, S, & Z in variable amounts.
Used when INR ≥ 1.5 as 25-50 IU/kg of factor IX (but usually administered for factor VII activity) but inconsistent concentration of factors, may contain heparin, from several donors, and limited availability.

Recombinant activated factor VII (rFVIIa)
Combination with vitamin K and clotting factor replacement and dosed as 10-90 mcg/kg iv but short acting, may cause thrombosis (< 10%), and costly (~$1000/mg).
between PCC, FFP and vit K what one increases INR the most
PCC>FFP>vit K

growth of the bleed is related to INR therefore with the admin of PCC bleed growth was less
Emergency Management of Coagulopathic ICH Patients
vit K
FFP
PCC
Restarting Anticoagulation in an ICH patient
Who?
Benefit > risk
Prosthetic cardiac valves (stroke risk ≥ 4%)
Secondary prevention in atrial fibrillation (stroke risk ≥ 12%) (those who have had a stroke)
Risk > benefit
Primary prevention of nonvalvular stroke (stroke risk ≤ 5%) – e.g. atrial fibrillation without a prior stroke
When?
No large, prospective trials in ICH patients
Data suggest a low risk of thromboembolic complications 7-14 days after reversal in patients with prosthetic valves (start slowly)
Clinical practice: delay for 1-6 weeks after ICH
what is the goal BP for stroke management right after a stroke
180/130
what meds are use in stroke patients for BP
labetolol
esmolol
nicardipine
enalaprilat
fenoldopam
nitroprusside
why is BP maintained at a higher than normal level after a stroke
to make certain the brain is still being profused
Subarachnoid Hemorrhage (SAH)
Mortality rate of ~ 50% and 1/3 of survivors require supplemental care. Cerebral vasospasm contributes to neurologic morbidity.
Pathophysiology: Rupture of vascular aneurysm.
risk factors for SAH (know)
age, female, hypertension, low body mass, alcohol consumption, current smoking, non-Caucasian.
protective factors for SAH (know)
high cholesterol, diabetes, use of hormone replacement
Hunt and Hess grades for SAH
I: asymptomatic or mild HA (mortality rate 5-10%)

II: moderate to severe HA, or occulomotor plasy (mortality rate 5-25%)

III: confused, drowsy, or mild focal signs (mortality rate 10-35%)

IV: stupor (localizes to pain) (mortality rate 35-70%)

V: coma, seizures (posturing or no response to pain) (mortality rate 50-100%)
Therapy of SAH Surgical manipulation:
Clipping ruptured vessel vs. coiling (inserting a “spring” into the ruptured vessel).
Reduces the rate of death or dependence at one year (23.7% vs. 30.6%, p=0.019).
Greatest benefit observed with coiling.
grade > 2
Therapy of SAH Prevent cerebral vasospams:
Approximately 2/3 of patients develop vasospasms, typically 3-12 days after SAH.
Pathophysiology likely related to return of oxygenated hemoglobin which stimulates release of endothelin (a vasoconstrictor), generates reactive oxygen species, and causes lipid peroxidation. Intracellular Ca increases.
Diagnosed clinically by sudden deterioration of neurologic function and via transcranial ultrasonography to detect increased blood flow velocity.

patient will look great and then quickly deterioate
what is the standard of therapy to prevent cerebral vasospams
CCB
Calcium Cannel Antagonists (CCAs) and cerebral vasospams
Calcium Cannel Antagonists (CCAs):
Prevent calcium release to reduce extent of vasospasm (do not decrease frequency).
Nimodipine 60 mg po q4hrs or nicardipine 2.5-15 mg/hour iv infusion.
Duration: 21 days.
Meta-analysis of 16 trials (3361 patients) showed reduced risk of poor outcome (RR=0.81, 0.72-0.92) but results driven by studies with nimodipine.
Concern is hypotension.
standard of therapy
idecreases Ca influx
decrease the extent but not the frequency
Mg and cerebral vasospams
Magnesium:
Acts as muscle relaxant (vessel wall).
Magnesium sulfate 8 g/day iv starting within four days of SAH.
Meta-analysis showed reduced risk of poor outcome (RR=0.75, 0.57-1.00) when added to CCAs.
statins and cerebral vasospams
Reduce vascular inflammation, inhibit smooth muscle proliferation, decrease platelet aggregation, and promote NO release.
Studies of simvastatin 80 mg daily or pravastatin 40 mg daily starting within 48 hrs of SAH show reduced biomarkers of brain injury, reduced blood flow velocity, less severe vasospasms but clinical outcomes not yet proven.
triple H therapy and preventing cerebral vasospams
Hypertension, Hypervolemia, Hemodilution:
Infuse intravenous fluids to achieve daily positive fluid balance.
Provide vasopressors to achieve supranormal blood pressure.
Hemodilution to allow blood to flow.
Goal is to keep arterioles patent.
Studies have shown mixed results but some components of this practice are routinely used.
Concern is fluid overload.

increase volume in the vessels to decrease the spasm
Treating Cerebral Edema (all causes)
Cerebral Perfusion Pressure (CPP) = MAP – Intracranial Pressure (ICP).
Goal is to maintain CPP by decreasing ICP or increasing MAP.
Intravenous mannitol 25-50 g as needed for serum osmolality 310-320 mOsm/kg.
Decreases ICP by acting as osmotic to reduce cerebral edema but also enhances blood rheology (ability of RBCs to conform to vessel).
Intravenous saline to serum Na of 145-150 mEq/L.
Decreases ICP by acting as an osmotic to reduce cerebral edema. Concern is fluid overload.
Hyperventilation to PCO2 ~ 35 mmHg.
Decreases ICP: CO2 is a vasodilator so reducing it causes vasoconstriction to reduce blood flow to edematous areas. Concern is too much vasoconstriction to impair blood flow to region.
Barbiturate therapy.
Decreases ICP. Several side effects including hypotension, bowel dysfunction, prolonged awakening (difficult neuro assessments), hepatic enzyme inducers, etc. May use other agents (propofol).
Hypothermia to ≥ 32 °C.
Neuroprotective but associated with arrhythmias, coagulopathies, electrolyte/glucose abnormalities, and shivering.
Vasopressors:
Increases MAP. Concern is peripheral ischemia.
Surgical decompression:
Decreases ICP by removal of brain tissue.
JC is a 72-y.o. African American man who
presents with ICH
HPI: he was found “down” by his wife after she made a 5-minute trip to the mailbox
He is currently unconscious, and was intubated for airway protection
CT scan: left-sided ICH
Vitals: BP 198/115 mm Hg; HR 99 bpm; temp 99.8°F; height 6’1”; weight 87 kg
Neuro: 6 on Glasgow coma scale (15 = normal, 8 = severe deficit)
PMH: atrial fibrillation, hypertension, hypercholesterolemia
Home meds: warfarin 5 mg daily, amlodipine 10 mg daily, atorvastatin 20 mg daily at bedtime
Labs: INR 3.1
JC was admitted to the neuroscience ICU 2 hours after symptom onset and needs emergent neurosurgical intervention
What would you recommend for therapy of this patient?
vit K
FFP
factor VII
what can be done to maintian cerebral profusion
increase MAP or decrease ICP
cerebral perfusion pressure (CPP)=
MAP-ICP
Repeat CT scan 2 hours after admission shows no further growth of ICH
INR is now 1.4
JC was rushed to surgery for evacuation of the hematoma and is doing well postoperatively
Repeat CT at 24 hours shows no hematoma growth
On day 2, you notice JC has a right facial droop and right-sided weakness
He is diagnosed with acute ischemic stroke (AIS)
What would you recommend for therapy of this patient?
ASA
Stroke:
focal neurological deficit lasting > 24 hours
TIA: (know)
Focal neurological deficit lasting < 24 hours
No evidence of infarction - Important determinant of stroke
90-day risk as high as 10.5% - greatest within 48 hrs
10% risk within 10 days
15% risk within 30 days
once have one likely to have another or a full stroke
classification of strokes
isschemic (85-95%)
* atherosclerotic(thrombosis)
*cardiogenic embolism
Hemorrhage (10-15%)
*intercerbral
*subarachnoid
Thrombotic Stroke
Thrombus formation in an artery
Reduced blood flow distal to an occlusion
Embolic fragment that breaks off and travels to a more distant vessel

age and HTN increase the risk

can block small vessels and not have any symptoms at all

most commonly lin the carotid artery
pathophys of Thrombotic Stroke
plaque formation with foam cells, derived from macropahges and CD4 t cells, cholesterol--> plaque becomes unstabe and ruptures-->cholesterol core is expsoed-->platelets are activated-->a thrombus forms
Secondary Prevention of stroke Risk Factor (RF) Reduction
Hypertension
Diabetes Mellitus
Smoking
Dyslipidemia
Others
RF Reduction: Hypertension for stroke
Avoid lowering blood pressure in the acute phase
Begin antihypertensive treatment once stabilized when patients are “beyond the hyperacute phase”
(want to continue to profuse the brain)

Joint National Committee (JNC) – 7
Compelling indication: Prevention of Recurrent Stroke
“recurrent stroke rates are lowered by the combination of an ACE Inhibitor and thiazide-type diuretics”
(beginning when the patient is stable (3-4 weeks out) gradually decrease BP
progress trial (stroke)
(Perindopril Protection Against Recurrent Stroke Study)

6,105 Patients
TIA/Stroke within 5 years (71% ischemic stroke)
2,916 (48%) were hypertensive

Perindopril 4mg
+
Indapamide 2.5mg
(n = 1770, 58%)

Perindopril 4mg
+
Placebo
(n = 1281, 42%)

Placebo
(n = 1280, 42%)

Placebo
+
Placebo
(n = 1774, 58%)

Mean follow-up: 4 yrs

important mono and dual thereapy vs. placebo
primary outcome of the progress trial
fatal or non-fatal stroke in active vs. placebo
PROGRESS Trial - Results
if had a stroke due to a plaque in carotid arteies likley to have an MI

if have HTN received benefit from dual therapy of ACE and diuretic

there was no benefit from single drug therapy
PROGRESS Trial - Results
active vs. placebo
Active vs. Placebo
10% in active group
13.75% in placebo group
Combination therapy reduced risk by 43%
Similar stroke risk regardless of baseline BP

Blood pressure reduction (mm Hg)
Active treatment vs. placebo: 9.0/4.0
Combination: 12.3/5.0
Perindopril alone: 4.9/2.8
NNT or NNH=
1/ARR
ARR
absolute risk reduction
PRoFESS Trial - Results
Telmisartan vs. Placebo
Mean of 2.5 years follow-up
Mean bp reduction = 3.8/2.0 mmHg
No difference in recurrent stroke or major cardiovascular events

did not decrease BP enough to see a significant difference

more long term benefit than acute
Antihypertensive conclusions and stroke
Degree of blood pressure lowering may be more important than specific agents
Once stabilized, aim for a reasonable goal of < 130/80
BP reduction will also reduce risk for other CV events
RF Reduction: Diabetes for stroke
No large RCT’s showing reduction of secondary stroke with tight glycemic control
Recommendations:
Glucose control to near normal levels to reduce microvascular complications
Goal HgbA1c to < 7%
RF Reduction: Lipids for stroke
Ischemic atherosclerotic stroke = CHD Risk Equivalent
LDL goal of < 100 mg/dL
Optional LDL goal of < 70 mg/dL for “very high risk”

Established CVD, plus 1 of the following:
Multiple Major Risk Factors (especially diabetes)
Severe and poorly controlled risk factors (especially continued smoking)
Multiple risk factors of the metabolic syndrome (especially TG’s > 200 mg/dL and HDL < 40 mg/dL

go with the option of <70
Evidence to support “statins” in atherosclerotic stroke
Heart Protection Study (HPS)
20, 536 patients with CAD, occlusive vascular disease (including CVD), diabetes, or hypertension with other vascular risk factors
Simvastatin 40mg/d vs. placebo
Overall 25% RRR for the endpoint of stroke (p < 0.0001)
Subgroup analysis: Those with preexisting CVD
Reduced coronary events and fewer revascularization procedures
Stroke was NOT significantly reduced

Stroke Prevention by Aggressive Reduction in Cholesterol Levels Study (SPARCL)

1st trial to directly assess the efficacy of statins in the secondary prevention of atherosclerotic stroke
SPARCL trial
4, 731 patients - ischemic (66%), hemorrhagic (2%), or TIA (30%) within 1-6 months
Average age = 63 years; LDL of 100 to 190 mg/dL
Exclusion: cardiac sources of emboli, SAH
No known coronary disease

atrovastatin 80mg
Placebo

Primary Endpoint: first nonfatal or fatal stroke
Follow-Up: ~ 5 year follow-up
SPARCL Trial results
Results
Mean LDL Values
Atorvastatin 80mg group: 73 mg/dL
Placebo group: 129 mg/dL

Primary Outcome
265 strokes in the atorvastatin group, 311 in the placebo [0.84 (0.71 to 0.99), p = 0.03]
2% Absolute Risk Reduction (ARR)
Treat 50 patients to avoid recurrent stroke (NNT)

Results - Secondary Outcomes
Any cardiovascular event
Atorvastatin 22.4%
Placebo 29%
0.74 (0.66 to 0.83), p < 0.001
RF Reduction: Smoking Cessation for stroke
Strong evidence showing smoking as a major independent risk factor for ischemic stroke
No RCTs of quitting smoking after stroke
Strongly advise every patient with TIA or stroke who has smoked in the last year to quit
Variety of options: Chantix® (varenecline), bupropion, nicotine replacement therapy, counseling
RF Reduction: Other for stroke
Alcohol consumption
Those with TIA/stroke who are heavy drinkers should eliminate or reduce consumption
Light to moderate levels may be considered – 2 drinks per day for men, 1 drink for nonpregnant women
Obesity (BMI >30 kg/m2)
Strongly related to many risk factors
No studies evaluating weight reduction and stroke risk
Weight loss can improve risk factors
Weight loss with goal BMI of 18.5 to 24.9

Physical Activity
Improvement in stroke risk factors
For those capable of engaging in physical activity, at least 30 minutes of moderate-intensity physical exercise
For those with disability, physical therapy recommended
risk factor reduction for the secondary stroke prevention
class 1a:
1. ACE and thiazide
2. glucose control to near normoglycemic levels
3. statin for those with elevated cholesterol, comorbid CAD, or evidnece of atherosclerotic origin
4. smoking cessation
5. antiplatelet agents rahter than oral anticoagulation
class IIa:
1. reduce BP by 10/5 mmHg to an optimal goal of <120/80 (happy with 130/90)
2. statin therapy for those with preexisting indication (eg: elevated cholesterol, comorbid CAD, atherosclerotic disease)
Antiplatelet Agents and stroke
Reduce the risk of both recurrent stroke and other cardiovascular events
Aspirin
Ticlodipine (Ticlid®)
Clopidogrel (Plavix®)
Aspirin/Dipyridamole (Aggrenox®)

all work on different areas of the platelet
Mechanism
Dipyridamole
Inhibits uptake of adenosine into platelets, resulting in elevated local concentrations of adenosine.
By acting on the platelet A2–receptor, the increase in concentration of adenosine stimulates platelet adenylate cyclase and in turn increases the levels of cAMP resulting in platelet inhibition
Clinical Trials – ASA/Clopidogrel
CAPRIE (1996)
19,185 with recent ischemic stroke, recent MI, or symptomatic peripheral arterial disease
Aspirin 325 mg/d vs. Clopidogrel 75 mg/d
Small benefit favoring clopidogrel
No benefit of clopidogrel in the stroke subgroup
Bottom line: Clopidogrel may be better than aspirin
does clopidogrel show benefit over ASA
showed a small benefit in the CAPRIE trial
Clinical Trials – ASA/Clopidogrel MATCH trial
Recent stroke or TIA
ASA 325 mg + Clopidogrel 75 mg vs. Clopidogrel
No difference in reducing stroke or vascular events
Increased risk of major or life-threatening bleeding
Bottom line: No benefit with combo, more bleeding. Important note: combination therapy is used for coronary artery stenting.

increases the risk of a bleed
Clinical Trials – ASA/Clopidogrel CHARISMA trial
At risk for CV event population
Clopidogrel 75mg + ASA (75-162mg) vs. ASA
Bottom line: No benefit with combo, more bleeding
ESPRIT Trial
2, 739 with TIA or stroke of presumed arterial origin w/in 6 months
Rankin score < 3

Aspirin (30-325 mg/d) +
ER Dipyridamole 200mg BID

Aspirin (30-325 mg/d) +
Placebo

Primary Outcome: death from vascular causes, non-fatal stroke, non-fatal MI, major bleeding
Mean follow-up: 3.5 years
ESPRIT Trial results
34% of those allocated to the combination discontinued their trial medication. 26% reported headache as one of the reasons.

Aggrenox is better than ASA for preventing stroke
PRoFESS Trial
20,333 patients 50 years or older with recent TIA or ischemic stroke

Aggrenox® (ASA 25mg + ER dypiridamole 200mg) twice daily

Plavix® (clopidogrel 75mg) daily

Primary Outcome: recurrent stroke of any type
Mean follow-up: 2.5 years

results: very similar resutls no significant difference
putting it al together for strokes
Clopidogrel may be better than aspirin
ER Dipyridamole/ASA better than ASA alone
Clopidogrel vs. ER Dipyridamole/ASA have similar efficacy (secondary prevention)

plavix is better for patients with heart problems
Summary of stroke stuff
Risk Factor Reduction
Hypertension: treat with ACEI + diuretic (amount of lowering more important); treat those with bp > 130/80
Diabetes: tight glycemic control
Dyslipidemia: LDL-C goal < 100 mg/dL (< 70 mg/dL in “very high risk”)
Others
Antiplatelet agents
Aspirin - historical data supporting its use, inexpensive
Clopidogrel – expensive, may be better than aspirin
ER Dipyridamole/ASA – expensive, may be difficult to tolerate, similar efficacy to clopidogrel
Common Clinical Scenarios for stroke (know)
Antiplatelet failure
Stroke while optimally treated with agent
Adherence confirmed
Co-morbidities
Interacting drugs
Options
Higher dose aspirin
Plavix® or Aggrenox®
Cost comparisons of ASA, plavix, aggrenox
ASA: generic $5

plavix 75mg brand $165.99

aggrenox 25/100mg $179.98
Antiplatelet Agents for Secondary Stroke Prevention
class 1a recommendation
1. Antiplatelet agents rather than oral anticoagulation
2. Aspirin (50-325 mg/day), the combination of aspirin and extended-release dipyridamole, and clopidogrel are all acceptable options for initial therapy
3. The combination of aspirin and extended-release dipyridamole is suggested over aspirin alone.
4. Clopidogrel for patients allergic to aspirin
class 1b:
1. Long-term use of aspirin + clopidogrel combination therapy should be avoided
class IIb:
1. Clopidogrel monotherapy over aspirin monotherapy
Common Clinical Scenariosfor stroke
(know)
Antiplatelet failure
Stroke while optimally treated with agent
Adherence confirmed
Co-morbidities
Interacting drugs
Options
Higher dose aspirin
Plavix® or Aggrenox®

MI (+stents) with TIA/Stroke
ASA + Plavix® for 1 year
Risk of re-stenosis vs. bleeding
Diagnostic difficulty
Atherosclerosis (large vessel, lacunar)
ICH, cardioembolism

Cost + Adherence
Seniors patient – N.O.
Aggrenox® expensive, poor adherence
Questionable platelet failure
BP control bigger problem
AG is a 64 year old male who presents to your clinic 3 weeks after being hospitalized for a stroke. As a result of the stroke, he walks with a cane and has slightly slurred speech. He did not have evidence of an intracranial hemorrhage and a carotid ultrasound showed bilateral atherosclerotic plaques. He was discharged from the hospital on his previous medication.
Current Medications:
Acetaminophen, tamsulosin, finasteride, nicotine patch, metformin, glyburide
Fasting labs:
TC = 202, HDL = 42, LDL = 122, TG = 110
HbA1c = 7.9%, SrCr = 0.9
Vital signs:
BP: 138/88; HR: 80; wt: 198; ht: 69 inches
Smokes 3/4 ppd

What will you do to reduce his risk for a second stroke or other vascular event?
statin
ASA