Stroke 2 Flashcards
ACUTE ISSUES
• Supportive
- prevent comp
Supportive • Vomiting • Airway • Oxygenation • IV fluid
Prevent Complications • Dehydration • DVT • Electrolyte imbalances • Fever • Hypertension • Hyperglycemia • Hem transformation • Infection • Intracranial pressure • Seizures
DEHYDRATION
• Manage with IV fluid (NaCl 0.9% - normal saline) or enterally (PO/NG PRN) • AVOID using: • Dextrose solutions • Hypertonic solutions • Hypotonic solutions
DVT PROPHYLAXIS
• Common due to immobility (hemiplegia)
• Prophylaxis options:
• First line: UFH/LMWH +/- Sequential compression device
• Heparin 5000 units SC BID (TID dosing in morbidly
obese)
• Dalteparin 5000 units SC Daily (7500 units in morbidly
obese)
• Tinzaparin 4500 units SC Daily (8000 units in morbidly
obese)
• Wait 24 hours post tPA
• ASA
• Give until ambulatory
ELECTROLYTE IMBALANCES
- SIADH occurs in 10-14% of patients
- Monitor daily lytes
- Correct imbalances prn
FEVER
• 1/3 of patients febrile within hours after stroke onset
• Causes include CNS deregulation, DVT, or infection
• Fever associated with poorer outcomes, increased
mortality
• Acetaminophen treatment of choice
• Impact of therapy on outcomes not established
HYPERTENSION
• Common due to loss of cerebral autoregulation (or pain or increased ICP)
• Only treat in first 24 hours if BP > 220/120mmHg (if no IV tPA/EVT given)
or concomitant conditions requiring antihypertensive agents
• Rapid decrease avoided first 7-10 days
• Theory to avoid decreased perfusion to ischemic area
• More aggressive BP monitoring and lowering if received IV tPA/EVT
(target SBP < 185, DBP < 110)
• Bottom line: treat “cautiously” (decrease ~15% of SBP/day)
• Can use PO/SL captopril, or IV labetalol/hydralazine/enalaprilat acutely
• How to manage anti-hypertensive meds from pre-admission?
• Recent studies (SCAST, COSSACS, CATIS) have not clarified issue
• No benefit, but not harmful? Serious flaws with studies
HYPERGLYCEMIA
• Associated with larger infarcts and worsened
prognosis
• Target BG of 8-10 mmol/L (GIST-UK)
• BBIT or insulin infusion to keep BG < 10
• Avoid hypoglycemia
• Difficult to control BG with tube feeds in NG patients
HEMORRHAGIC TRANSFORMATION
• 5-30% incidence
• Hemorrhagic infarction
• Bleeding into ischemic/dead brain tissue
• Not usually associated with symptoms
• Parenchymal hemorrhage
• Hematoma formation in viable brain tissue
• May have severe clinical consequences
• Risk appears directly correlated with time to reperfusion of
ischemic region
• Antiplatelet therapy may or may not be held depending on size
of hemorrhage; clinical judgment required on case by case basis
INTRACRANIAL PRESSURE (ICP)
• Common cause of early death (24-96 hours post
stroke)
• 10-20% develop edema requiring clinical intervention
• Manifested by decreased LOC, worsening neurologic
deficits
• Therapeutic options:
• Mild fluid restriction
• Mannitol 0.25-1 g/kg IV q6h PRN until serum osmolality ~
300 or increased ICP resolves (no data)
• Hypertonic saline (3% Na)
• Surgery (hemicraniectomy)
• Steroids provide NO bene
INFECTION
increased risk for
• Increased risk for: • Aspiration pneumonia • UTI (catheters) • Secondary septicemia • Monitor and treat prn • Pneumonia should be treated early as major cause of death after stroke
SEIZURES
• Most common cause of new-onset seizures in the elderly
• No data regarding using prophylactic anticonvulsants
• Treat only if seizures occur
• “Provoked” seizure and thus typically short duration of
therapy (months)
• Duration of therapy also affected by how close seizure
occurs to acute event
• Many drug interactions with anticonvulsants!
Ischemic Stroke
ì What was the cause?
ì Cardioembolic (Afib, CM, LVT, valvular disease, etc) ì Large vessel atherosclerosis ì Small vessel disease ì Cryptogenic ì Other
RISK FACTOR MANAGEMENT
secondary stroke prevention
- HYPERTENSION
- 28% RRR in recurrent stroke if treat hypertension (PROGRESS)
- Perindopril +/- indapamide treatment of choice
- Many agents studied – “Bottom line” decrease BP
- Benefit for normotensive patients as well
• DYSLIPIDEMIA
• 2.2% 5 year ARR in recurrent stroke (SPARCL)
• Atorvastatin 80mg PO daily treatment of choice
• Small increase in ICH in treatment group but found to be hypothesis
generating
• Start statin in patients regardless of LDL if stroke thought to be of
atherosclerotic origin
• PCSK9 Inhibitors (evolocumab, alirocumab
Major trials: FOURIER (evolocumab) ODYSSEY-OUTCOMES
(alirocumab)
- At 48 weeks, decreased LDL ~59%, ischemic stroke RRR 25%, no major adverse effects, ~$8400/year, NNT ~74 over 2.2 years
- GLAGOV – Evolocumab showed coronary plaque regression (statin + evolocumab/placebo) over ~1.6 years
- DIABETES
- SMOKING
SURGICAL INTERVENTION
secondary stroke prevention
- Carotid artery stenosis
- Symptomatic high-grade stenosis (50-99% on vascular imaging)
- ?Asymptomatic stenosis
- Intervention:
- Carotid endarterectomy (CEA)
- Carotid stenting
• CEA
• Patient must be on just ASA prior to procedure (bleed risk of DAPT too
high)
• Stent
• Patient loaded with ASA (325-650mg) and clopidogrel (300-600mg)
prior to stenting and kept on DAPT for 6-12 weeks (data lacking)
ANTIPLATELET VS. ANTICOAGULATION
• Depends on source of ischemic stroke
• Antiphospholipid antibody syndrome =
anticoagulation
• Cerebral venous sinus thrombosis = anticoagulation
• Cancer associated thrombosis = anticoagulation
- Cardioembolic = anticoagulation
- A-fib
- Mechanical heart valve
- Poor LV function (EF<35%)
- LV thrombus
- Rheumatic stenosis
• Most other causes = antiplatelet
RISK STRATIFICATION FOR A-FIB (CHADS2)
CHADS2 pof 2 at least with stroke
• 0 points and <65 = no antithrombotic
• 0 points + CAD or PAD = ASA 81mg daily
• >1 point OR >65 years of age = anticoagulation
Which DOAC is clearly superior to other
DOACs in terms of preventing ischemic stroke
from non-valvular atrial fibrillation?
- Dabigatran
- Apixaban
- Rivaroxaban
- Edoxaban
- It’s a trap! There is no clearly superior DOAC
- It’s a trap! There is no clearly superior DOAC
DOACs – a PANACEA?
• Advantage is no INR monitoring
• Reduced ICH but more GI bleeds with dabigatran and
rivaroxaban
• Guidelines favour their use however…
• Are still anticoagulants
• Require careful selection in renal dysfunction
• No real guidelines on weight extremes (<50kg, >120kg)
• Alberta Blue Cross coverage
• Drug interactions – p-glycoprotein/CYP3A4 pathways
• Phenytoin, Carbamazepine, AVRs, Antifungals, Abx…
-> many on pheny and carba
• Danger of “fire and forget”
• Monitoring tool – thrombosiscanada.ca
DOACs – Antidotes
• DOACs not easily reversible – dialysis, activated charcoal, PCC
(Octaplex) are not very effective if bleeding occurs
• Idarucizumab (Praxbind) – first approved reversal agent for any DOAC in Canada; reverses dabigatran (RE-VERSE AD)
• Monoclonal antibody fragment that binds dabigatran with an affinity
350 times greater than thrombin
• Binds free and thrombin bound dabigatran
• Andexanet-alfa – in development for Xa inhibitors
• Aripazine – in development as universal DOAC antidote
WARFARIN VS ASA FOR NON A-FIB
• WARSS
• Compared warfarin vs. ASA in non-cardioembolic
ischemic strokes
• No significant difference found in primary end point of death or recurrent stroke. No sig diff in rates of majornhemorrhage
• WASID
• Compared warfarin vs. ASA in intracranial arterial
stenosis strokes or TIAs
• Trial stopped early due to significantly higher rates of
adverse events in the warfarin group
INITIATING ANTICOAGULATION
secondary prevention
• How long should you wait post stroke if initiating AC for Afib?
• Within 3-14 days is reasonable per CSBPR 2020
• “The larger the infarct the longer you wait”; hem transformation
- wait 6 days for moderate stroke
- the sooner you start the greater the chance of staring hemorrhage
• Stroke neurologists/pharmacist will decide based on clinical experience
• “Bridge” with ASA(14 days) (i.e. patient will be on ASA 81mg daily until it is time to start anticoag. If starting warfarin, usually “bridge” with ASA nstead of therapeutic LMWH/IV UFH)
• If active clot or mechanical valve will initiate AC sooner
• Warfarin – wait until INR therapeutic for 48 hours then stop ASA/DVT prophylaxis
• DOAC – stop ASA/DVT prophylaxis upon initiation of AC
which antiplatemet
secondary prevention
we tipically go with aspirin
- ASA
- Decreases recurrent stroke/TIA risk by ~15% (RRR) vs placebo
- “ASA Failure”- remains a mystery on how to best manage
- Clopidogrel
- No significant benefit over ASA (CAPRIE)
- Ticagrelor
- Failed to show superiority of ticagrelor over ASA (SOCRATES)
- ASA + Clopidogrel (dual)
- Increased benefit (CHANCE, POINT)
- Only used in TIA/minor stroke (NIHSS 3 or less) due to risk of hemorrhagic transformation
- 21-30 days only then step down to single antiplatelet (only this long but longer -> bleed)
• ASA + Ticagrelor
• Increased benefit of ASA + Ticagrelor x 30 days (THALES)
• No reduction in disability. Increased bleed. NIHSS <=5
(though ~60% <=3). Much more expensive than clopidogrel
Are more antiplatelets better?
secondary
adding 3 (asa +clopid + dipyridamole)
Results
• No difference in the incidence or severity of
recurrent ischemic stroke
• Statistically significant increase in frequency and
severity of bleeding
Typical Duration of DAPT (before step-down
to monotherapy) after a stroke
• Minor stroke/TIA
• 21-30 days
- drop to asa everyday
- Stent (i.e. internal carotid artery stent)
- 6-12 weeks – guided by neurosurgery
- Intracranial Atherosclerosis
- 90 days
ANTICOAGULATION + ANTIPLATELET?
• Rivaroxaban 2.5mg BID + ASA 100mg daily vs Rivaroxaban 5mg BID vs ASA 100mg daily (COMPASS)
was not a stroke study but found it was good
• Essentially a study in patients with stable CAD with atherosclerosis
• Part of exclusion criteria: Stroke within 1 month, any history of hemorrhagic or lacunar stroke
profound when looking specifically at
the reduction in ischemic stroke: (60 [1%] of 8313 vs 120 [2%] of 8261; hazard ratio [HR] 0·5
• Full dose anticoagulation + antiplatelet?
• Afib + carotid or intracranial stent
• Acute coronary syndrome + stroke
• If patient would normally be on an antiplatelet for stroke prevention, but they are on anticoagulation for a different reason (e.g. DVT/PE), we would typically stop the antiplatelet until anticoagulation is finished, then restart
= the antiplatelet
Cryptogenic / ESUS
no athero, non smoker, no risk factors
many are cardioembolic that was not catched w instrument
• Antiplatelet or Anticoagulant? Antiplatelet!
• NAVIGATE ESUS
• Rivaroxaban 15mg daily vs ASA 100mg daily
• No difference in rate of recurrent stroke
• Statistically significantly more major bleeding in Rivaroxaban arm
- more of a failed trial
- RESPECT ESUS
- Dabigatran 150mg BID (or 110mg BID) vs ASA 100mg daily
- Non-statistically significant reduction in stroke in Dabigatran arm
- Increase in clinically relevant non-major bleeding in Dabigatran arm
So far it seems like only the elderly or people
with medical conditions have strokes… Do
young, healthy people have strokes?
yes
CEREBRAL VENOUS SINUS THROMBOSIS (CVST)
Cervical Artery Dissection (CD)
CEREBRAL VENOUS SINUS THROMBOSIS (CVST)
- Thrombosis occurring in the venous circulation leading to infarction +/- bleeding
- More frequent in women, and more frequent in children and young adults.
- Symptoms: Headache +/- typical stroke symptoms
- Mortality <5%, and ~80% of patients recover fully
- Treatment: LMWH/IV UFH -> oral anticoag
- Traditional risk factors for thrombosis:
- Pro-thrombotic medications (e.g. estrogen, birth control)
- Pregnancy and purperium
- Infections
- Thrombophillias (APLAS, F5L, etc)
- Myeloproliferative disorders/malignancies
- Smoking
- Dehydration
- In ~13% of cases there are no risk factors
Cervical Artery Dissection (CD)
• Most frequent cause of stroke in young people
• CD accounts for 2% of all ischemic strokes, but accounts for 8% - 25% of strokes in patients
under 45 years old
• Can be spontaneous or traumatic
- Risk factors associated with CD:
- Trauma
- Hypertension
- Oral contraceptives
- Genetic disorders affecting connective tissue
- Migraine
- Common trauma that can cause CD:
- Motor vehicle collision
- Coughing, sneezing
- SPORTS – heavy lifting, golf, tennis, yoga, contact
- Cervical manipulative therapy
• Treatment = antiplatelet OR anticoagulation
• Antiplatelet unless patient has indication for anticoag
UFH for 1 week, if not gone will use warfarin?
TIA MANAGEMENT
ì HIGH RISK – symptom onset within 48 hours
ì need urgent brain/vessel imaging, ECG
ì INCREASED RISK – symptoms 48 hours to 2 weeks
ì fluctuating/persistent symptoms should be seen
within 24 hours
ì with no neurologic deficits should be seen within 2
weeks
ì LOWER RISK - > 2 weeks from symptom onset
ì should see neurologist within 1 month
TIA WORK-UP
• After risk assessment:
• Same investigations as stroke patients based on specified
timeline (vessel imaging, echo, holter, labs)
• Start antithrombotic (remember CHANCE/POINT)
• CEA or stenting if symptomatic carotid artery stenosis
• Risk factor management
• HTN, lipids, diabetes, smoking cessation
INTRACEREBRAL HEMORRHAGE (ICH)
In Canada, ICH accounts for ~10-15% of all strokes
• Mortality is much higher than seen in ischemic strokes (40%
vs 15%)
- Supportive measures
- DVT prophylaxis
- Pneumatic compression stockings start in first 24 hours
- LMWH or UFH after 48-72 hours if bleed stable
- BP management
- Current standard of practice acutely target SBP < 180mmHg
- Targeting < 140mmHg acutely: No harm, yet no benefit seen
- Bottom line treat far more aggressively than in ischemic strokes
- Long-term BP target <130/80mmHg
• Surgical intervention in select patients
SUBARACHNOID HEMORRHAGE (SAH
Supportive measures
• Determine the cause:
Aneurysm? CVST?
As blood passes through the weakened blood vessel, the blood pressure causes a small area to bulge outwards like a balloon.
- Surgical intervention
- If aneurysmal:
- Nimodipine 60mg PO q4h x 21 days
- Vasospasm and possibly neuroprotective
- Improved outcomes (mortality, neurologic outcome)
SUBDURAL HEMATOMA (SDH)
• Supportive measures
• Determine the cause: Usually traumatic. Could, however,
occur from intracranial hypotension, coagulopathy, or in
association with antithrombotic therapy
• Could be acute or chronic
• Require neurosurgical consultation/intervention
HEMORRHAGIC STROKE + ANTIRHROMBOTICS
• When to re-start antithrombotic after SAH or ICH?
• Depends on etiology of bleed (ex. Amyloid, hypertensive, AVM) and location (deep vs lobar)
• Depends on size of bleed
• Depends on compelling indication for antithrombotic
• Bottom line is to decide on a case by case basis in
consultation with stroke neurologist
• CSBPR 2020: “The optimal timing and strategy regarding antithrombotic therapy following an ICH is uncertain and should be individualized to the patient (Evidence level C)”
The big picture
• Take Away
• Pharmacist role is important for stroke prevention
• Stroke is often an endpoint of numerous modifiable
risk factors – modify them!
• Afib should almost always be anticoagulated
• Ensure doses/regimens of antithrombotics are
correct for the condition
• On DAPT for stroke? – double check duration
• Drug interactions with antithrombotics – be vigilant
