PMY3304- STROKE AND TRANSIENT ISCHAEMIC ATTACK

What is the WHO definition of a stroke?

stroke is a clinical syndrome, of presumed vascular origin, typified by rapidly developing signs of focal or global disturbance of cerebral functions lasting more than 24 hours leading to death.

what are the types/classification of stroke?

• ischaemic stroke (85%)- blockage of blood flow to brain leading to cell death

• Haemorrhagic stroke (15%)- caused by bleeding in the brain

• Transient ischaemic attack (TIA)- ischaemic blockage lasting <24 hours

what are the non-modifiable risk factors of stroke?

• increasing age, ethnicity (black, south african)

• family Hx

• male sex

• personal Hx of CVD, AF, HF, heart defect, valvular disease, carotid artery disease, migraine (with aura), CKD, sickle cell disease

• lack of social support

• socioeconomic status

what are the modifiable risk factors of stroke?

• excess alcohol

• diabetes (poor glycaemic control)

• poor diet

• dyslipidaemia

• overweight/ obesity

• hypertension

• smoking

• physical inactivity

• pregnancy

• medication- COC, oral HRT

• pollution

what are the haemorrhagic-specific risk factors for stroke?

• head injury (present to hospital)

• illicit drug use (heroin, cocaine, amphetamine)

• anticoagulant use

• cerebral aneurysm

• arteriovenous malformations

how do stroke/TIA present?

Face (has their face fallen on one side? can they smile?), Arms (can they raise both arms and keep them there?, Speech (is their speech slurred?), Time (call 999 if you see any single one of these signs)

what areas of the brain are affected by strokes?

• frontal lobe- executive functions, thinking, planning, organising and problem solving, emotions and behavioural control, personality

• motor cortex- movement

• sensory cortex- sensations

• parietal lobe- perception, making sense of the world, arithmetic, spelling

• temporal lobe- memory, understanding, language

• occipital lobe- vision

usually the affected side of the body is the opposite to the side of the brain affected, the short and long term effects of stroke will depend on the area of the brain impacted

what are the other potential symptoms of stroke?

• sudden weakness, numbness, paralysis of 1 side of body

• sudden loss/ blurring of vision

• dizziness, unsteadiness, sudden fall

• sudden memory loss or confusion

• sudden loss of speech/difficulties

• balance & coordination problems

• sudden, severe headache resulting in a blinding pain unlike anything experienced before/ thunderclap (haemorrhagic)

• syncope/ loss of consciousness

how is stroke diagnosed?

1. screen using validated screening tool e.g. FAST- if positive, refer to specialist stroke service ASAP

2. brain scan (ASAP- within 1hr arriving at hospital), CT and/or MRI— confirm diagnosis & whether ischaemic/ haemorrhagic

3. rule out hypoglycaemia (blood glucose)

4. Other important aspects but should not delay arrival to hospital

• Clinical features and history= time/speed of onset, risk factors e.g. past medical/ family Hx, medications e.g. anticoagulants, insulin, anti-hypertensives

• Examination and investgations= neurological exam, CV exam, vital signs/ NEWS2- HR, BP, O2 saturation etc., ECG (arrhythmia?), cholesterol, HbA1c/ blood glucose, BP, renal function (?risk factors/ secondary prevention)

what is the aetiology of ischaemic stroke/ TIA?

two most common causes are:

1. Atherosclerosis- fatty plaques develop in arteries carrying blood from heart to brain. Plaques can rupture forming a clot.

2. AF- irregular, inefficient heart pumping meaning heart doesn’t empty fully after each beat. pooled blood can clot & travel to the brain lodging in a blood vessel

what is the potential affect ischaemic stroke/ TIA on the brain?

• interruption of blood flow through intracranial arteries leads to deprevation of oxygen, glucose and nutrients

• leading to necrosis and cell death

who can fibrinolysis be administered by?

fibrinolysis can only be administered within a specialist stroke service with:

• trained staff & equipment to administer and manage complications

• immediate access to imaging and staff trained to interpret these

what is the eligibility criteria for fibrinolysis e.g. alteplase, tenecteplase?

1. rule out bleed- haemorrhagic stroke must be excluded by appropriate imaging (CT/MRI)

2. Timing

• all patients with acute stroke regardless of severity within 4.5 hours of known symptom onset

• consider if within 4.5-9 hours only if imaging shows the potential to salvage brain tissue

why are there time limits for fibrinolysis treatments?

more effective when started earlier, lower risk of complications

can fibrinolysis be given if the patient has had a haemorrhagic stroke?

NO WILL MAKE THE PATIENT WORSE

what fibrinolysis drugs are commonly used?

alteplase and tenecteplase- given IV, dose based on weight

what is the moa of fibrinolysis?

dissolve fibrin clot, removing blockage in arteries and restoring blood flow

what are the side effects of fibrinolysis?

anaphylaxis, haemorrhage (intracranial, GI), recurrent ischaemia or angina, hypotension, HF and more…

when is fibrinolysis C/I?

largely linked to high bleeding risk e.g. haemorrhagic stroke, recent surgery, recent GI ulcer, severe uncontrollable HTN (aim to reduce BP to <185 systolic, <110 mmHg diastolic before giving)

what is a thrombectomy?

• highly skilled procedure in which blood clots are removed mechanically rather than broken down by medicines (fibrinolysis)

• requires detailed, strict imaging and assessment by specialist

when would a thrombectomy be used?

used to treat those with severe stroke to reduce their risk of long term disability

NO STENTING IN STROKE!!!!

what should be offered to non-AF patients who have had an ischaemic stroke as ongoing stroke prevention?

Offer the following ASAP to everyone presenting with acute stroke who has had a diagnosis of haemorrhagic stroke excluded by brain imaging

• within 24 hours of presentation if not eligible for fibrinolysis OR

• wait 24 hrs after fibrinolysis to commence

ANTIPLATELET

ASPIRIN 300mg PO OD 2/52 weeks then switch to clopidogrel PO 75mg OD lifelong as secondary prevention

What should be considered alongside anti-platelets?

consider a PPI if high GI bleed risk (care with choice- lansoprazole or pantoprasole) interaction between omeprazole, esomeprazole and clopidogrel

what is a risk with clopidogrel in relation to pharmacogenomics?

patient could potentially be clopidogrel resistant if there are recurrent strokes/ TIA while the patient is taking clopidogrel

what kind of drug is clopidogrel?

it is a pro-drug requiring activation by CYP2C19 metabolism to have antiplatelet activity

do NICE recommend genotype testing when prescribing antiplatelets?

yes NICE recommends genotype testing to aid antiplatelet choice in ischaemic stroke/ TIA

alternative antiplatelets should be used for secondary prevention if the person has CYP2C19 loss of function e.g. aspirin 75mg OD

when are anticoagulants used with stroke?

• not routinely used in strokes without AF

• Long term anticoagulation is needed if the person has had an ischaemic stroke due to AF

What does anticoagulant use for stroke need to be balanced with?

needs balanced with early bleed risk post-stroke

• high risk of fluid/blood in the infarcted area

• risk of haemorrhagic conversion, delay commencing until patient stabilised

what anticoagulant should be prescribed to patients with ischaemic stroke?

aspirin 300mg OD for up to 2/52 weeks the consider anticoagulation instead of clopidogrel longterm- for most patients this will be a DOAC

can an antiplatelet be given to prevent clots for a stroke caused by AF?

NO an anti-platelet will not prevent the clots formed due to potential blood pooling

give some examples of anticoagulations and standard dosing

• Dabigatran 150mg BD

• Rivaroxaban 20mg OD

• Apixaban 5mg BD

• Edoxaban 60mg OD

• warfarin

• LMWH

how is TIA classed and when should patient be seen?

• most TIAs are thought to resolve within 1 hr but can persist for up to 24 hours

• patient should be assessed within 24 hours of symptom onset by a specialist stroke clinician. If symptoms more than 7 days previous, should be assessed ASAP within 7 days.

• Ischaemic stroke classed as ‘minor’ that do not have persistent symptoms, can be managed in the same way. interventions are necessary to reduce risk of more severe stroke

can fibrinolysis be used to manage TIA?

blockage has been resolved but patient remains high risk for full-blown ischaemic stroke

can anti-platelets be used to manage TIA?

• DAPT can be used if not C/I

• high dose loading dose (single dose) then standard dose- DAPT x21 days then lifelong monotherapy

• can give a 300mg aspirin single dose and a clopidogrel 300mg single dose and then followed by aspirin 75mg OD and clopidogrel 75mg OD (DAPT) for 21 days- monotherapy thereafter with clopidogrel 75mg OD

why can patients not go on an anticoagulant straight after an ischaemic stroke?

patient cannot go on an anti-coagulant straight away because there is a risk of stroke changing from ischaemic to haemorrhagic- therefore aspirin is given for up to first 2 weeks

what is an alternative regimen after a TIA?

aspirin (300mg stat then 75mg daily thereafter) and ticagrelor (180mg stat then 90 mg BD) DAPT for 30 days followed by monotherapy- remember genotypic testing for clopidogrel

when can long term anticoagulation be given for a TIA?

only if recognised indication e.g. AF as soon as intracranial bleeding is excluded

what antiplatelets is usually used to manage TIA?

aspirin + P2Y12

How can blood pressure be managed as secondary prevention of stroke and TIA?

• most important risk factor for first and recurrent stroke

• causes approx. 50% of ischaemic strokes and is principal risk factor for intracerebral haemorrhage

• stroke guidance recommended lower clinic BP target of <130mmHg systolic (or home BP <125mmHg)—- if tolerated

how can lipid levels be managed as secondary prevention of stroke and TIA?

• high intensity statin- atorvastatin 80mg

• monitor FLP and LFT at baseline, 3 & 12 months then continue FLP annually (creatinine kinase if muscle pains)

• ESC guidelines recommend tighter control with LDL <1.4mmol/L and a 50% reduction in LDL from baseline

• if not achieved, review adherence, diet, lifestyle, increase dose (if possible) and consider additional therapy e.g. ezetimibe or injectables

how can diabetes be controlled as secondary prevention of stroke and TIA?

• check for potential new diagnosis- HbA1c

• optimise pharmacological and non-pharmacological management if poor control

• SGLT2i regardless of glycaemic control could be considered given high CV risk

how else can stroke and TIA risk be lowered?

• deprescribing

• review contraception

• review HRT

• review meds that can increase CV risk (NSAIDs, febuxostat, anabolic steroids)

• review meds that increase bleed risk (NSAIDs, DAPT duration)

how can contraception increase stroke and TIA risk?

• combined oral contracepetives (oestrogen and progestogen) can increase stroke risk and should be stopped/ not offered following stroke/ TIA

• alternative lower risk hormonal (e.g. progestogen only pill, LNG-IUD, injectionn, implant) or non-hormonal (e. copper IUD) are preferred

how can HRT increase stroke and TIA risk?

• oral HRT slightly increase stroke risk and should be stopped/ reviewed

• transdermal HRT doesnt increase stroke risk and could be considered, specialist input and risk vs benefit discussion required

what stepwise approach should be used when choosing licensed products to prevent stroke & TIA?

step 1- licensed alternative used as licensed e.g. switching from oral tablet to other formulations (e.g. liquid) or route (e.g. transdermal)

step 2- licensed medicine used ‘off label’ e.g. opening a capsule/ crushing a tablet and dispersing in water or food or giving medicines via feeding tube— if possible e.g. NEWT guidelines

step 3- special order product as a last resort

what are other important considerations when undertaking medicine optimisation?

• prescribing responsibility (licensing) and cost

• bioavailability differences when switching formulations e.g. lithium

• administration issues (e.g. off label administration)

• medicines not to crush e.g. most MR

• Liquids aren’t always best- has the person SALT review?

• review again once swallow improved

• is the med still needed (deprescribing?)

what is the difference between a haemorrhagic stroke and a ischaemic stroke?

haemorrhagic is immediately more serious than ischaemic- higher mortality rate

about 15% strokes are haemorrhagic- split between intracerebral haemorrhage and subarachnoid haemorrhage

how is haemorrhagic stroke managed via surgery?

may be required to remove haematoma and relieve intracranial pressure (decompressive hemicraniectomy) OR coiling or clipping to halt the bleed

how can anticoagulation be reversed rapidly?

to return clotting levels to normal- vitamin K or DOAC reversal agent

how is the MDT involved in stroke rehabilitation?

• complications of stroke are numerous, vast and long term in many cases

• specialist stroke rehabilitation teams are comprised of multiple health care professionals from different disciplines to help best meet patients’ needs

• required both in secondary care and in the community on discharge

what are the early complications following stroke?

• haemorrhagic transformation of an ischaemic stroke

• cerebral oedema

• delirium

• seizures

• venous thromboembolism (DVT/PE)

• cardiac complications e.g. MI, HF, AF (shared aetiology)

• infection e.g. aspiration pneumonia

what are long term complications of haemorrhagic stroke?

• mobility problems- e.g. weakness, falls, spasticity

• sensory problems e.g. touch, temperature, pain

• continence problems

• pain- neuropathic (nerve damage) or MSK (immobility)

• fatigue

• problems with swallow, hydration, nutrition

• sexual dysfunction

• skin problems e.g. pressure sores

• visual problems e.g. diplopia, blurred vision

• cognitive problems e.g. dyspraxia, dementia

• difficulties with ADL

• psychosocial problems e.g. anxiety, depression

• communication problems e.g. aphasia

• financial problems- loss of income

• end of life care