Stroke - WordPress.com Transient ischemic attack (TIA): abrupt onset focal neurological deficit that...
Transcript of Stroke - WordPress.com Transient ischemic attack (TIA): abrupt onset focal neurological deficit that...
Stroke:
Transient ischemic attack (TIA): abrupt onset focal neurological deficit that lasts <24 hours and usually <30 minutes
May or may not result in infarction
Treat as stroke until tissue damage is ruled out on imaging
Highest risk of stroke after a TIA is in the first few days
- 2 days: 3.5%, 30 days: 8%, 90 days: 9.2%
ABCD2 score used to predict the short term risk of stroke after TIA
Stroke: cerebrovascular accident
Classified into two major types:
1. Hemorrhagic – brain hemorrhage due to intracerebral hemorrhage or subarachnoid hemorrhage
- Results in direct irritant effects of blood that is in direct contact with brain tissue
- Causes include cerebral artery aneurysm, arteriovenous malformation, hypertensive hemorrhage and trauma
2. Ischemic – brain ischemia due to atherosclerosis of cerebral vessels, thrombosis, embolism (to cerebral arteries) or systemic
hypoperfusion
Pathophysiology: Normal cerebral blood flow: ~50mL/100g per minute – maintained by cerebral autoregulation
Ischemia: ↓ blood flow: <20mL/100g per minute – cerebral autoregulation is impaired
When blood flow <12 mL/100g per minute – cerebral autoregulation effect is diminished ↓ ATP ↑ Ca damage + cell death
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ISCHEMIC STROKE
Definitions:
Infarct: Necrotic region of tissue
Lacunes: small lesions
Penumbra: surrounding infarct – activated neurons that could survive for days
- if perfuse right away, can salvage
Hemorrhagic Transformation: ischemic tissue transformed to hemorrhage
- an intracerebral hemorrhage from thrombolysis often occurs as a result of hemorrhagic transformation of ischemic tissue
- 2 types: asymptomatic + symptomatic asymptomatic believed to be clinically innocuous (but controversial)
TOAST Classification:
Large artery atherosclerosis
Cardioembolism AFib, valve disease, ischemic heart disease, infective endocarditis
Small-vessel occlusion (Aka lacune)
Stroke of other determined etiology Prothrombotic state, dissections, drug abuse
Stroke of undetermined etiology
Risk Factors:
NON-MODIFIABLE MODIFIABLE, well-documented Potentially modifiable, less well documented
ISCHEMIC STROKE
Age (↑2x/10 years over 55) Gender (♂↑risk,
♀↑complications) Race (↑death in Asians, African
Americans, Hispanics) Family history of stroke Personal history of stroke Low birth weight Sickle cell disease
Hypertension Atrial fibrillation Other cardiac diseases TIA CAD Diabetes Dyslipidemia Alcohol, diet, smoking Sickle cell disease Asymptomatic carotid stenosis Physical inactivity, obesity Drugs: Post-menopausal HRT
Oral contraceptives Migraine Drug and alcohol abuse Hemostatic and inflammatory factors Sleep disordered breathing
INTRAPARENCHYMAL HEMORRHAGE
Vascular malformation Amyloid angiopathy Neoplasm Trauma Acute ischemic stroke
Hypertension Antithrombotic use Thrombolytic Use Coagulopathy Illicit Drug Use
Presentation:
CNS Headache Vertigo Altered LOC Falling Sudden numbness of leg, arm or face
HEENT Loss of vision Double vision Visual field defects Aphasia – trouble speaking Dysarthria
MSK One-sided weakness Hemiparesis Sudden issue with coordination
Neurological deficits and signs of symptoms correlate to location of infarct
Complications:
Early Complications (within 7 days)
Cerebral edema and herniation (within 96 hours)
Expansion of the infarct/recurrent infarction
Hemorrhagic transformation weakened vessels ↑ risk of hemorrhage
Seizures risk present in acute and chronic phase of stroke
Aspiration pneumonitis
Pneumonia dysphagia/swallowing difficulties ↑ risk of aspiration pneumonia
UTI risk ↑ especially if required to insert a foley catheter
VTE
Late complications (> 7 days later)
Clinical depression
Recurrent stroke
Seizure
Aspiration pneumonitis
VTE
Decubitus ulcer
Persistent cognitive or language dysfunction and/or persistent loss of mobility
Spasticity
Scores:
ABCD2 score: helps justify if should be managed as in-patient or out-patient stroke clinic
National Institutes of Health Stroke Scale: Performed upon admission to determine type of care and to assess progress of stroke
Modified Rankin Score (*Often used as outcomes in stroke RCTs): Global score
Differential Diagnosis: Clinical situations mimicking stroke
Psychogenic Lack of objective cranial nerve findings, neurological findings in a non-fascicular distribution, inconsistent examination
Seizures Hx of seizures, witnessed seizure activity, post-ictal period
Hypoglycemia Hx of diabetes, low serum glucose, ↓ LOC
Migraine with aura Hx of similar events, preceding aura, headache
Wernicke's encephalopathy Hx of ETOH abuse, ataxia, ophthalmoplegia, confusion
CNS abscess Hx of drug abuse, endocarditis, medical device implant with fever
CNS tumour Gradual progression of sx, other malignancy, seizure at onset
Drug Toxicity Lithium, phenytoin, carbamazepine
Laboratory Tests:
Diagnostic Tests:
*Head CT – Computerized Tomography – Identifies ischemia and arterial occlusions – Most commonly used imaging test (immediate availability) – Difficulty visualizing deep, small infarcts
*CTA – Computerized Tomography Angiogram – Focuses on the blood vessels
*Almost all patients will get head CT or CTA, unless poor renal function
If above negative but still high suspicion of stroke, use MRI stroke protocol (long waitlist)
MRI – Magnetic Resonance Imaging
– More sensitive than CT in detecting ischemic changes and acute vs chronic origin
– Greater spatial resolution
– Expensive; limited availability
– CI: pacemakers, metal implants (e.g. in eye), claustrophobia, patient confusion, etc.
Other tests:
♦ MRA – Magnetic Resonance Angiogram: Detects intracranial stenosis, vessel occlusion
♦ Transcranial Doppler – Identification of intracranial stenosis
– Has been used to monitor thrombolysis effects and to determine prognosis
♦ ECG – baseline CV assessment, detection of arrhythmia, concurrent MI
♦ TTE/TEE – examine if any clots in the heart
GoTs:
1. Reduce the ongoing neurological injury
2. Restore quality of life and function
3. Prevent complications, 2o to immobility and neurological dysfunction
4. Decrease mortality
5. Prevent stroke recurrence
Ischemic Stroke Continuum
Primary Prevention Hyper-Acute Acute Stroke Treatment Secondary Prevention
Timing Prior to stroke < 6 hours Days 1 – 14 (> 24 hours) > Day 14 – 30
Goal ↓ risk of first stroke Prevent early mortality and morbidity
↓ risk of recurrent stroke
Management Control risk factors Oxygen, BP, glucose, temperature, volume status, reperfusion
Antiplatelet or TPA + Supportive Care + VTE Prophylaxis
Antiplatelet + Control Risk Factors
Treatment for Ischemic Stroke:
1. OXYGEN – Hypoxemia = low concentration of oxygen in blood
Common causes: Partial airway obstruction, Hypoventilation, Aspiration, Atelectasis, Pneumonia
Supplemental O2 – for patients with SaO2 < 95% - Goal: >92% (evidence is not conclusive)
o If normal oxygen saturation, not required routinely
2. POSITIONING
Supine: use if patient is NOT hypoxic – may offer advantages in term of cerebral perfusion
Elevate head of bed to 15-30o: if patient at risk of obstruction, aspiration, ↑ intracranial pressure
3. BLOOD PRESSURE MANAGEMENT
Hyperacute: Hypertension is common in acute stroke patients and ↑ risk of sICH (symptomatic intracranial hemorrhage)
♦ Ischemic stroke patients eligible for thrombolytic therapy
– Treat to a target < 180/105 mmHg
– May reduce the risk of intracranial hemorrhage
♦ Ischemic stroke patients not eligible for thrombolytic therapy
High ID of intracranial stenosis (50-99%)
~90% negative predictive value
– Only treat extreme BP elevation (SBP > 220mHg or DBP > 120mmHg)
– Goal: ↓ BP by ~15% but not more than 25% over 1st
24 hours
High BP:
– PROs: could improve cerebral perfusion of ischemic tissue
– CONs: could exacerbate edema and hemorrhagic transformation of ischemic tissue; encephalopathy, cardiac complications, renal insufficiency
(transformation: when have ischemic tissue and then it bleeds in the area)
No consistent evidence to support BP targets post-ischemic stroke; aggressive BP lowering may ↓ perfusion and worsen ischemia
Options: may need to start NG tubes to give meds regularly as there are complications with fluctuating BP meds
Not receiving tPA *GOAL: ↓ 15% BP* Receiving tPA *higher bleeding risk ∴ target BP < 185/110 for initiation and <180-105 for maintenance
– within 48 h of ischemic stroke/TIA target SBP < max of 220mHg and DBP < 120 *Do not lower unless >220/120*
– Discontinuing or holding BB therapy may lead to rebound tachycardia or rapid afib. Stopping BB to meet BP targets is not recommended, although a lower dose may be considered
– Consider holding a patient's normal antihypertensive regimen on medication reconciliation form. Consider maintaining BB therapy as per above.
– Physician to R/A BP regimen 48 hours after stroke/TIA when patient is neurologically stable
Options: ♦ Captopril 12.5-25mg SL Q30 min PRN SBP>220 and/or DBP>120 – Max dose 150mg/24 hrs
Options: ♦ If systolic BP > 180mmHg *OR* diastolic BP > 105mmHg – IN CRITICAL AND SPECIAL CARE AREAS ONLY:
Labetalol 10mg IV, then 10-20mg IV Q10min PRN (Max dose: 300mg/24h) Contact physician if BP not controlled after 3 doses HOLD labetalol if HR < 60BPM MONITOR BP 5, 10 and 15 minutes after each dose VS and neurovital signs Q15min until 4 hrs after BP controlled *OR*
– Hydralazine 5-10mg IV Q15min PRN Contact physician if BP not controlled after 3 doses Monitor BP 15 and 30 mins after each dose of hydralazine VS and neurovital signs Q15min until 4 hours after BP controlled
– Captopril 12.5mg SL Q30min PRN (Max: 150mg/24h)
4. VOLUME STATUS
Hypovolemia hypoperfusion, exacerbation of ischemia, renal impairment
Hypervolemia ↑ brain edema, stress on myocardium
Hypotonic solutions (ie D5 ½NS) may worsen edema because they distribute intracellularly
NS distributes more evenly into extracellular spaces
Recommendation: Use isotonic solutions for volume replacement (0.9% NS)
5. GLUCOSE MANAGEMENT
Hyperglycemia: common during acute stroke (40%)
- Stress reaction impaired glucose metabolism
- Associated with ↑ infarct volume by MRI
- ↑ risk of sICH in patients treated with rtPA – tPA is contraindicated if BG < 2.7 or > 22 mmol/L
Hypoglycemia: rare (likely related to antidiabetic meds)
*stroke mimics and seizures – look for autonomic and neurological symptoms and check blood glucose*
Target: 7.7 – 10 mmol/L for all hospitalized patients
6. TEMPERATURE
Hyperthemia in acute ischemic stroke – associated with poor neurological outcomes and worsening of stroke
o ~1/3 of admitted stroke patients will be hyperthermic within 1st
hours of acute stroke onset
Determine cause – e.g. secondary to a cause of stroke (infective endocarditis), complication of stroke (pneumonia, UTI, sepsis)
Treat the cause if identified
Antipyretics to ↓ temperature if hyperthermic (>38oC)
- Insufficient evidence to support hypothermia to ↓ metabolic demands (goal is to avoid fever)
7. FIBRINOLYSIS
Alteplase (Recombinant Tissue Plasminogen Activator):
Alteplase binds to fibrin in a thrombus and converts entrapped plasminogen to plasmin which dissolves the clot
(thrombus: strands of fibrin + plasminogen) ∴ helps re-perfuse and save cells in penumbra (original infarction remains)
- Onset: <1 hr
- Duration: Fibrinolytic activity persist up to 1 hr after infusion terminated
- Elimination: primarily hepatic – t1/2: 5 minutes
- Dose: 0.9mg/kg (max 90mg), 10% given as bolus, 90% infused over 1h
Indications:
1. Diagnosis of ischemic stroke causing measurable neurological deficit *AND*
2. Patient has been assessed by a neurologist, CT scan performed and read, can be transported if necessary and alteplase treatment can
be initiated within 4.5 hours of a well established symptom onset
Goal: door to needle time < 60 mins for tPA – time is brain!
- Blood glucose is the only lab test that must precede tPA administration
o Unless hx of anticoagulant use, abnormal bleeding
Contraindications
Absolute Contraindications: History of intracranial hemorrhage, neoplasm, vascular
malformation (except meningioma), or aneurysm Stroke, intracranial surgery or head injury within 3 mos Arterial puncture at non-compressible site within 7 days Symptoms of stroke suggestive of subarachnoid hemorrhage Witness seizure with postictal residual neurological impairments
unless clearly attributable to acute stroke Evidence of active bleeding or acute trauma (fracture) on exam Acute bleeding diathesis Persistent hypertension (BP >185/110) Anticoagulant use within 48 hrs and a prolonged PTT and/or
INR > 1.7 (Anti-Xa levels take too long) Platelet < 100,000 x 10
9/L
Blood glucose < 2.7 mmol/L or > 22 mol/L CT changes showing major extensive early infarct signs Evidence of intracranial hemorrhage on pretx noncontrast head
CT
Relative Contraindications: Recent acute MI (within previous 3 months) Neurological signs clearing spontaneously; signs minor & isolated Pregnancy Age less than 18 years Within 14 days of major surgery or serious trauma Recent GI or urinary tract hemorrhage (within previous 21 days) Post MI pericarditis or aortic dissection
Precautions within 3-4.5 hrs following onset of stroke symptoms: Oral anticoagulant treatment Age > 80 yo Severe hemispheric stroke as assessed clinically (NIHSS score >
25) or a stroke with major early infarct CT signs involving more than 1/3 of the middle cerebral artery territory
Combination of previous stroke and DM Major surgery or trauma within previous 3 months
Monitoring:
Vital signs Q15min x 2 hours, then Q30min x 6 hours, then Q1hr until 24hr post-tx
Neurovital signs Q1hr x 6 hrs, then reassess Signs of clinical deterioration: new headache, acute
hypertension, nausea or vomiting, evidence of bleeding Angioedema CT head – repeat 24 hours after alteplase
Precautions:
No tooth brushing or shaving x 24hr Avoid central venous access and arterial punctures x 24hr Avoid placing indwelling catheter during infusion and for at
least 30 mins after Avoid insertion of an NG tube in the 1
st 24hrs
Toxicity Monitor for Plan
Severe Bleed Cerebral, retroperitoneal, genitourinary, respiratory tract, gastrointestinal
D/C alteplase CBC
Minor Bleed Superficial hematoma, hematuria, hemoptysis, epistaxis, gingival bleeding
D/C alteplase? CBC
Intracranial Hemorrhage New onset H/A, N/V, new onset symptoms D/C alteplase CT scan CBC
Orolingual angioedema reactions
Swelling of tongue, lips or oropharynx (Risk↑in ACE-I, infarctions w/ insular/frontal cortex)
D/C alteplase IV diphenhydramine 50mg, IV methylprednisolone or hydrocortisone 100mg, IV ranitidine 50mg, Manage airway – when resolved and angioedema was mild, may restart tPA Epinephrine: use should be weighed against risk of sudden HTN and ICH
Acute HTN BP >180/105 mm Hg IV antihypertensive
Q15min vitals
If there is clinical deterioration (new headache, acute HTN, nausea and vomiting) or evidence of bleeding:
D/C tPA infusion
CT scan STAT
INR, fibrinogen, CBC
Evidence for tPA:
NINDS: 2 Part RCT, R, PC, DB n= 654, ICH ruled out. tPA 0.9mg/kg within 3h of stroke onset.
– Bottom line: Functional benefit at 90 days, but ↑ risk of ICH. No mortality benefit.
ECASS III: R, PC, DB n = 821. Included patients with sx onset within 3-4.5h. tPA 0.9mg/kg vs.placebo
– Bottom line: If treated between 3-4.5h, functional benefit (mRS<2) at 90 days persists but smaller.
IST-3: Open lab, PC < n = 3035. Acute ischemic stroke, sx onset within 6h, ICH ruled out. No age restriction.
tPA 0.9mg/kg within 6 hr of symptom onset.
– Bottom line: No functional benefit, higher risk of early death within the 1st
6 days
Endovascular therapy 6 positive trials published in 2014-2015
Indicated for: > 18 yo, functionally disabling stroke (NIHSS >2, ASPECTS >6), can be performed +/0 tPA treatment, imaging (small to
moderate ischemic core), intracranial artery occlusion (in the anterior circulation, mod to good collateral circulation, r/o ICH)
o Exclusion: BP > 185/110, IV tPA > 0.9mg/kg, evidence of coagulation abnormalities
Time to tx: within 6hr of symptom onset, up to 12 hrs
– Must be transferred to a stroke centre with expertise in 2nd
generation stent retrievers (only at VGH)
Good functional outcome at 90 days (mRS < 2) but existing conflicting studies/results
8. ANTI-PLATELET THERAPY:
If NOT on antiplatelet + NOT receiving tPA: 160mg-325mg ASA STAT after imaging excludes ICH and dysphagia screening performed
– acute ASA therapy ↓ risk of early recurrent ischemic stroke
If treated with TPA: delay ASA until 24 h post-thrombolysis scan has excluded ICH
In all patients: continue ASA 81 – 325mg daily indefinitely or until alternative anti-thrombotic started
o Clopidogrel may be considered in patients on ASA prior to stroke or TIA as an alternative
o If dysphagic, ASA may be given by enteral tube (80mg daily) or 325mg PR daily
Might consider combination of ASA and clopidogrel for initiation within 24 hours of a minor ischemic stroke or TIA and for continuation
for 90 days
o But…Longer-term use of ASA 81mg and clopidogrel 75mg is not recommended for the use for secondary stroke prevention due
to an increased risk of bleeding and mortality
Evidence:
IST, 1997 (N=19435): ASA 300mg within 48h of stroke onset vs. Placebo (f/u: 14 ds + 6 mos)
– ARR 1.1% for recurrent ischemic stroke (NNT 83 @14ds), NSS for all-cause mortality + hemorrhagic stroke
CAST, 1997 (N=21106): ASA 160mg within 48h of stroke onset vs. Placebo (f/u: 4 wks + discharge)
– ARR 0.5% for recurrent ischemic stroke (NNT 200 @4wks), ARR = 0.6% (NNT 167 @4wks) for all-cause mortality, NSS for hemorrhagic
stroke + death – younger patients with different types of stroke, compared to IS
CHANCE 2013 (N=5170):
ASA 75-300mg LD 75mg daily x 21ds + clopidogrel 300mg LD 75mg daily x 90d vs. ASA 75-300mg LD 75mg daily + placebo
– Recurrent ischemic stroke: ARR 3.5% (NNT = 29 @90ds), NSS for all-cause mortality, hemorrhagic stroke, severe bleeding
– Chinese-only population with high stroke risk (NIHIS <4) which aren't as aggressively treated for HTN, diabetes, hyperlipidemia
– POINT trial extended and still enrolling for North American population
9. VTE PROPHYLAXIS
High risk of DVT and PE – more likely to occur in 1st
3 months after stroke
- PEs account for 10% of deaths after stroke
AHA/ASA 2013 Guidelines: SC administration of anticoagulants is recommended for tx of immobilized pts to prevent DVT
CHEST 2012 Guidelines:
- Initiate within 48 hrs after stroke onset. If admin alteplate, 24hr after admin of thrombolytic therapy (alteplase)
- Low dose SC heparin or LMWH (LMWH = UFH in prevent DVT; Heparin ↓ risk of DVT and PE by 60%)
Canadian Stroke Best Practice Guideline (2015): Based on CLOTS 3 – patients at high risk of VTE should be started on thigh-high
intermittent pneumatic compression (IPC) devices or pharmacological VTE Px immediately if no contraindication (e.g systematic or
intracranial hemorrhage. At present, there is no direct evidence to suggest the superiority of one approach over the other
o Monitor: skin integrity daily, wound care consult if skin breakdown begins (IPC ↑ risk of skin breaks)
IPC devices should be taken off when:
- Patient becomes mobile
- At discharge from hospital
- If any AEs develop
- After 30 days of use (whichever comes first)
Secondary Stroke Prevention:
1. LIFESTYLE MANAGEMENT
Healthy balanced diet: Mediterranean type diet – high in vegetables, fruit, whole grains, fish, nuts, olive oil
Sodium intake <2g/day
Exercise :
Goal: 150 mins of moderate to vigorous activity per week, >10 min per session
PT involvement at initiation if ↑ falls risk, comorbid disease
Weight: BMI 18.5-24.9 kg/m2 or waist circum < 88cm (women), <102cm (men)
Alcohol
- Women: max 10 drinks/week (no more than 3 drinks on a single occasion)
- Men: max 15 drinks/week (no more than 4 drinks on a single occasion)
OC and HRT – discontinue, consider alternatives
Recreational drug use – refer patients for support and resources for dealing with drug addiction
Smoking cessation – refer patients to smoking cessation clinic and BC Quit Now Program
Sleep apnea (risk factor)
– screen for sleep apnea in patients with stroke or TIA
– refer to sleep specialist for management of OSA
– avoidance of hypnotics, sedatives; weight loss; CPAP; dental appliances
2. BLOOD PRESSURE
Long-term management: First stroke: For every 10 mmHg ↑ in DBP, risk of stroke ↑ by 50%
10/5mmHg ↓ in BP is associated with 30-40% ↓ in risk of stroke
Study N Patient Population Intervention & Comparison Primary Outcome Recurrent Stroke
Cardiovascular & Cerebroavascular Stroke
HOPE Stroke
Sub-group analysis of HOPE
1013 with previous stroke
High risk cardiovascular
Ramipril 10mg1 vs. Placebo Composite
(MI, Stroke, CV death)
0
↓ for 1o stroke
0
PROGRESS R, DB, PC
6104 Stroke within previous 5 years +/- HTN
Perindopril 4mg vs. Placebo ↓ 5/3 mmHg
Fatal and non-fatal stroke
0 0
Perindopril 4mg + Indapamide vs. Placebo ↓ 12/5 mmHg
↓ ?effect d/t combo
or more ↓ BP
↓ ?effect d/t combo or
more ↓ BP
PRoFESS R, DB, PC Factorial
20,332 Ischemic stroke within 90 days
Telmisartan 80mg/d vs. Placebo (+ Standard of care – incl. other BP meds)
Recurrent Stroke 0
0
SPS3 R, Open, MC
3,020 Recent (<180d) lacunar stroke
SBP target 130-149 vs. SBP < 130
Recurrent stroke 0 0
Tips and Tricks
Blood pressure reduction
- Prevent recurrent stroke, cardiovascular events
- Benefit seen in hypertensives and normotensives
Absolute target BP not defined
- Benefits seen with 10/5 mmHg reduction
- CHEP < 140/90 mmHg, <130mmHg in diabetic patients
Lifestyle modifications and pharmacologic therapy
- Diuretic + ACEI reasonable option
- May begin >24 hours post-stroke, depending on stability (but not in the immediate acute phase of stroke)
3. ANTIPLATELET THERAPY
Options: ASA (80-325mg) daily; combined ASA (25mg) + ER dipyridamole (200mg) BID; or clopidogrel (75mg) daily
ATTC 2009 Meta-analysis: ASA vs. no antiplatelet therapy
1o Prevention:
– Serious vascular events (MI, stroke or vascular death): NNT 1667
– Ischemic stroke: NSS
– Extracranial bleeds: NNH 3334
2o Prevention:
– Serious vascular events (MI, stroke or vascular death): NNT 67
– Ischemic stroke: NNT 625
– Extracranial bleeds: very incompletely reported
Vascular mortality: NSS
Compared to ASA
Comparator (Comp)
Study Primary Outcome Bleeding Compared to ASA?
ASA Comp ASA Comp
Clopidogrel CAPRIE 1996
5.83% 5.32% 9.28% 9.27% SAME
ARR: 0.51; NNT 195 NSS
ASA + Clopidogrel CHARISMA 2006
7.3% 6.8% 1.3% 2.1% WORSE Similar efficacy but ↑ bleeding risk with DAPT + NSS for mortality
NSS P < 0.001
SPS3 2012
2.7% 2.5% 0.79% 1.7% SIMILAR with all-cause death benefit (2.1% vs.1.4%)
ARR: 0.2, NSS p < 0.001
ASA + Dipyridamole (not often well tolerated d/t headaches)
ESPIRIT 2006
16% 13% 3.85% 1.93% BETTER
ARR: 3; NNT 33 NSS
ESPS-2 1998
19% 14.9% 8.2% 8.7%
ARR: 4.1; NNT 24 NSS
Ticlopidine TASS 19% 17% Ticlopidine: Diarrhea, rash, neutropenia
?SIMILAR
ARR: 2%, NNT 50
Warfarin WARSS 2001
16% 17.8% RR 1.61 (1.38-1.89) ↑ minor hemorrhage, but NSS for major
WORSE Similar efficacy but ↑ bleeding risk with warfarin
ARR: 1.8%; NSS
Compared to Clopidogrel
Comparator (Comp)
Study Primary Outcome Bleeding Compared to ASA?
Clopidogrel Comp ASA Comp
ASA CAPRIE 1996
5.32% 5.83% 9.27% 9.87% SAME (more diarrhea and rashes than ASA)
ARR: 0.51; NNT 195 NSS
ASA + Clopidogrel MATCH 2004 (high risk pts)
12% 12% 1% 2% WORSE
NSS P < 0.0001, NNH = 50
ASA + Dipyridamole PRoFESS 2008
8.8% 9% 3.6% 4.1% ?SIMILAR but not non-inferior and not well tolerated
Not Non-inferior NSS
Tips and Tricks
Similar to ASA
- Clopidogrel
- Efficacy: Warfarin; Clopidogrel + ASA (but ↑ bleeding)
Superior efficacy to ASA
- ASA + Dipyridamoke
- Ticlopidine
- Both are less well tolerated than ASA
SIMILAR to clopidogrel:
- ASA + dipyridamole
Choose based on efficacy, safety, patient factors, cost
ASA reasonable first-line choice
– ANTIPLATELET MANAGEMENT IN PATIENTS WITH INTRACRANIAL ARTERIAL STENOSIS
SAMMPRIS Trial: Stenting vs. Aggressive Medical Therapy for Intracranial Arterial Stenosis
MC RCT. N = 451 patients with recent TIA/CVA due to IC artery stenosis
Percutaneous transluminal angioplasty and stenting (PTAS) + medical therapy vs. Medical therapy only (ASA 325mg daily for entire f/u +
Clopidogrel 75mg daily x 90 days)
o 1o outcome: Stroke or death within 30 ds after enrollment or after revascularization for qualifying lesion beyond 30 days
PTAS + Medical Tx: 20.5% vs. Medical Tx only: 11.5%, P = 0.009
SAMMPRIS was extrapolated to support use of DAPT for up to 3 months in patients with stroke or TIA 2o to ICA (severe stesnosis of 70-
99% of a major intracranial artery)…but no head to head trials of DAPT to ASA or plavix in this context
4. LIPID MANAGEMENT
Modest relationship between LDL and risk of stroke – Lower LDL lower risk of stroke
Target LDL of < 2mmol/L, or a 50% ↓ in LDL from baseline
SPARCL trial – atorvastatin 80mg daily if LDL > 2.6mmol/L (evidence is stronger with ator)
- Recurrent stroke HR 0.84 (NNT = 53 x5y), fatal stroke HR 0.57 (NNT =143), hemorrhagic stroke HR 1.66 (NNH = 107 – no excess fatal
hemorrhagic stroke)
- TNT: 80 vs 10mg (CVA HR 0.77, Stroke HR 0.75)
Heart Protection Study – simvastatin 40mg daily
- High risk cardiovascular patients – 1820 patients with previous stroke (not all patients had previous stroke/TIA)
- Simvastatin reduced vascular events, non-fatal stroke
- 27% RRR for stroke, 1.6% ARR, NNT = 63 x 5.5 yrs
Meta-analysis in high risk cardiovascular population
- Statins reduced the risk of stroke (OR 0.81)
Risk factors for statin-induced myopathy: dose of statin; advanced age (particularly > 80), female sex, possibly Asian descent, fraility,
polypharmacy/drug interactions, renal/hepatic dysfunction, genetic polymorphisms, alcohol
In a patient with a recent stroke…what is the optimal lipid-lowering strategy to reduce the risk of stroke?
SPARCL (Atorvastatin 80mg vs Placebo, N = 4731, Mean LDL = 3.43, Stroke or TIA within previous 1-6 months, no known CAD)
- High dose atorvastatin
↓ risk of fatal stroke, major coronary events
May be associated with more hepatotoxicity
Reasonable option in patients with
o Ischemic stroke
o LDL 2.6 – 4.9 mmol/L
Fibrates not effective at reducing stroke risk
5. DIABETES MANAGEMENT:
Diabetes: Established risk factor for ischemic stroke
Approximately two fold increased risk of stroke
Independent predictor of recurrent stroke
- 9.1% of recurrent stroke attributable to diabetes
In obese patients with T2DM, metformin
- Reduced macrovascular complications
- Reduced stroke
Study N Patient Population Intervention and Comparison Major Results
ACCORD 10,251 62 y/o, A1c 8.1%, T2DM< CV disease Intensive (A1c < 6%) vs. Conventional (A1c 7-7.9%)
Primary outcome: NSS Non-fatal stroke: NSS All-cause mortality: ↑ in intensive group
ADVANCE 11,140 66 y/o, A1c 7.5%, T2DM, CVD Intensive (A1c < 6.5%) vs. Conventional (A1c ~7%)
Macrovascular: NSS Non-fatal stroke: NSS Nephropathy: ↓ in intensive group
PROACTIVE 5,238 61 y/o; A1c 7.8%; T2DM, CVD, Stroke (19%)
Pioglitazone vs. Placebo Primary outcome: NSS Subgroup of previous stroke: ↓ CV events in pioglitazone group
Evidence lacking that diabetes control decreases risk of recurrent stroke. Manage diabetes by CDA guidelines.
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