Cerebrovascular Disease

Why is cerebrovascular disease important?

15 million people worldwide will suffer from a stroke each year. 30-43% risk of recurrent stroke within 5 years of first stroke. Effective early management can significantly reduce mortality and morbidity

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What is the definition of a stroke?

Defined by WHO - clinical syndrome of rapidly developing signs of focal (or global) disturbance of cerebral function. Lasting more than 24 hours of leading to death. No apparent cause apart from a vascular one

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What is a transcient ischaemic attack?

Transient ischaemic attack (TIA) - mini stroke with signs and symptoms lasting <24 hours

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Outline the pathology of a stroke (1)

Blood clot stops blood flow to an area of the brain. 80% due to ischaemic stroke. 15% due to intracerebral haemorrhage (bleed within the brain), 5% due to subarachnoid haemorrhage (bleed on surface of the brain)

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Outline the pathology of a stroke (2)

Lobar/deep haemorrhages with various different pathologies. Ischaemic stroke – 45% caused by atherosclerosis, 20% caused by ischaemic small vessel disease (Lacunar stroke), 15% caused by cardioembolic source (AF), 5% due to rare causes

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What are the non-modifiable risk factors for a stroke?

Age, ethnicity (Afro-Caribbean/Asian race), gender (male), FH of CVD, PFO (hole in heart), type 1 diabetes, AF

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What are the modifiable risk factors for a stroke?

High blood cholesterol, type 2 diabetes, obesity, smoking, alcohol consumption, drug use, lack of physical exercise, poor diet

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What are the signs and symptoms for a stroke? (1)

Usually occurs without warning. Symptoms dependent on area of the brain damaged (e.g. right side of brain damaged, left arm affected). Sudden weakness of face/arm/leg, often one-sided

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What are the signs and symptoms for a stroke? (2)

Other signs include sudden: numbness of face/arm/leg, confusion/loss of speech or understanding speech, problems with vision, difficulty walking, dizziness, balance, co-ordination. Sudden severe headache with no known cause, vomiting

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What are the signs and symptoms for a stroke? (3)

Reduced conscious level in intracerebral haemorrhage (ICH)

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What does FAST stand for?

Facial weakness (can the patient smile?). Arm weakness (can they raise both arms?). Speech (talk to them). Time (to call 999) - used to recognise stroke

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Describe the acute treatment for a stroke (1)

Acute stroke associated with a high mortality. Worldwide estimated 30 day case fatality rate is 16-23%. Cerebral infarct itself, haemorrhage, complications (early recurrent stroke, pneumonia, DVT, PE)

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Describe the acute treatment for a stroke (2)

Effective early management of acute stroke can reduce mortality and morbidity (time is brain)

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What is the aims for stroke treatment? (1)

Quick access to specialised acute stroke unit. Minimise damage to local brain tissue. Prevent any acute complications. Initiate treatment for secondary prevention

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What is the aims for stroke treatment? (2)

Ensure a comprehensive rehabilitation programme is established for each patient with occupational, speech and language and physiotherapy input

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State the options for management of acute ischaemic stroke

Thrombolysis, anti-thrombotic treatment, antiplatelets (aspirin, clopidogrel), anticoagulants (warfarin, DOACs), other drug treatments (HTN, lipid management)

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What is the aim of thrombolysis - rt-PA?

E.g. alteplase. Aims to minimise damage to local brain tissue by directly breaking down the clot to restore blood flow to the brain

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What is the mechanism of action for alteplase? (1)

Recombinant DNA version of tissue plasminogen activator protein (t-PA). Cleaves fibrinogen and fibrin matrix of clot. Given at a dose of 0.9 mg/kg, max 90 mg over 1 hour (10% as an IV bolus). Prompt treatment shown to improve outcome in stroke

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What is the mechanism of action for alteplase? (2)

tPA (tissue plasminogen activator), stimulated fibrinolysis, dissolves blood clots by activating plasminogen (cleaves to form plasmin). Plasmin (proteolytic enzyme) breaks cross-links between fibrin molecules. Clot is dissolved

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What are the licensing requirements for thrombolysis-rt-PA? (1)

Strict licensing requirements (it can only be used by a physician specialised in stroke care with facilities available to monitor its use and complications). Must be administered within 4.5 hours of stroke onset

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What are the licensing requirements for thrombolysis-rt-PA? (2)

Brain imaging must be performed before administration to exclude an intracranial haemorrhage. Full assessment of all potential contraindications. All patients registered into a monitoring study

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What are the licensing requirements for thrombolysis-rt-PA? (3)

Complications include transformation of stroke to haemorrhagic stroke

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Describe features of using aspirin in acute stroke (1)

Aspirin inhibits platelet aggregation and rationale for use in acute ischaemic stroke is to prevent further occlusion of blood supply. Two large RCTs-SCT and CAST trials investigated use of aspirin in 40,000 patients

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Describe features of using aspirin in acute stroke (2)

Demonstrated a reduction in 9 non-fatal strokes per 1000 patients. Aspirin is given as soon as possible after the onset of strokes symptoms (within 48 hours). 300 mg daily for first 2 weeks then switch to clopidogrel 75 mg OD

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Describe features of using aspirin in acute stroke (3)

If patient has dysphagia - can give aspirin PR or by enteral tube. If previous dyspepsia with aspirin give a PPI as cover

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Describe the acute treatment for BP control (1)

Hypertension is common (left untreated if BP < 220/120 mmHg). Due to pre-existing hypertension, pain, nausea, vomiting, high intracranial pressure, anxiety, stress of stroke. Continue with previous BP therapy. BP usually settle within a week

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Describe the acute treatment for BP control (2)

Awaiting trial evidence on effect of BP reduction. Use IV labetalol if BP >220/120 (only if hypertensive emergency)

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Describe features of acute treatment for other considerations (1)

Seizures can occur in 5% patients (can intensity brain injury from stroke, more common in SAH or cortical infarcts due to emboli). Choice of drug unclear (phenytoin common although consider interactions and TDM, levetiracetam commonly used now)

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Describe features of acute treatment for other considerations (2)

Thromboprophylaxis - risk of bleeding so no active treatment given

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What does secondary prevention mean?

Patients who have suffered a stroke remain at an increased risk of further stroke between 30-45% within 5 years. Risk of completing a stroke after TIA is 20% within a month

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Describe the antiplatelet therapy used for secondary prevention (1)

Clopidogrel 75 mg daily (lifelong). Not for acute management of ischaemic stroke (only recommended for use in patients in acute phase with a true aspirin allergy only)

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Describe the antiplatelet therapy used for secondary prevention (2)

CAPRIE trial demonstrated benefit of clopidogrel vs aspirin in long term post-stroke (5.3% vs 5.8% reduction in stroke/MI/vascular death). NICE guidance released in 2010 - considered a first line treatment option

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Describe the antiplatelet therapy used for secondary prevention (3)

Need to consider bleeding risk and consideration of PPI/GI cover (drug interactions also need to be checked)

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Describe features of dipyridamole (1)

Anti-platelet properties similar to aspirin alone. Previously recommended for use in combination with aspirin in patients who have had previous ischaemic event (since updated, now recommends clopidogrel). Dose of MR 200 mg BD

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Describe features of dipyridamole (2)

Common side effect - headache (often leads to withdrawal unless properly counselled, self-limiting and usually resolves within 7 days)

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Describe features of warfarin (1)

First line for patients with cardioembolic stroke (due to AF). Patients with AF are 5x at risk of developing a stroke. 60% risk reduction compared to aspirin 300 mg (40%) in primary prevention

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Describe features of warfarin (2)

All patients with AF should be considered for warfarin therapy (CHA2DS2VASC scoring). Similar benefit in secondary prevention. National clinical guidelines for stroke advise consideration of treatment 2/52 after acute event

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Describe features of direct oral anticoagulants (1)

E.g. rivaroxaban, dabigatran, apixaban. Directly target activity of thrombin or factor Xa. Block pro-coagulation activities involved in the formation of a fibrin clot

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Describe features of direct oral anticoagulants (2)

Situations considered in preference to warfarin (labile/poorly controlled on warfarin, issues with compliance of warfarin dosing, patients on compliance aids, allergy/adverse reaction to warfarin)

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What are the advantages of DOACs?

Similar or lower rates of both ischaemic stroke and major bleeding compared to warfarin. Convenience of dosing. Less dietary/drug interactions

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What are the disadvantages of DOACs?

Lack of a reversal agent (except dabigatran). Contraindicated in patients with CrCl <15 mL/min. Unable to monitor. Cost. Unanticipated ADRs

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What are the lifestyle recommendations for secondary prevention of a stroke?

Smoking cessation, diet and weight loss, reducing salt intake, exercise (increasing evidence), avoid excessive alcohol (increasing evidence)

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Describe features of BP control in secondary prevention (1)

Evidence shows that BP control in hypertensive patients can reduce incidence/recurrence of stroke. All patients with hypertension persisting >2 weeks should be treated. Targets - 140/90 (non-diabetic patients), 130/80 (diabetic patients)

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Describe features of BP control in secondary prevention (2)

Follow NICE guidance for hypertension management - <55 years (ACE-I/ARB), >55 years (Ca channel blocker). Step up to combine and add thiazide-like diuretic e.g. indapamide, spironolactone

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Describe features of statin therapy for secondary prevention (1)

Evidence suggests that statins reduce the risk of stroke (meta analysis demonstrate an 18% reduction). Current recommendations - statin therapy for all patients with a TIA or ischaemic stroke that can tolerate

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Describe features of statin therapy for secondary prevention (2)

Not started immediately post-stroke (leave 48 hours post). Research suggests additional mechanisms of action of statins (plaque stabilisation, anti-inflammatory and reduced disease progression of CAD)

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Describe features of statin therapy for secondary prevention (3)

Starting doses of simvastatin 20-40 mg daily or atorvastatin 10-20 mg daily

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Describe features of a carotid artery investigation for secondary prevention (1)

Carotid arteries carry main blood supply to the brain. Stenosis and narrowing of arteries lead to a significant risk of ischaemic stroke. Any patients with significant stenosis should be considered for carotid endarterectomy surgery

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Describe features of a carotid artery investigation for secondary prevention (2)

Can half the risk of ischaemic stroke. Risks associated with the surgery - stroke during surgery and nerve damage

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What is a carotid endarterectomy?

Removal of material from the inside of the artery to allow normal blood flow

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Summarise key concepts about cerebrovascular disease (1)

One of the most common causes of mortality in the UK. Lots of evidence to support the management of these patients. Aims of treatment - quick access to specialised stroke services, minimise damage to local brain tissue, prevent any acute complication

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Summarise key concepts about cerebrovascular disease (2)

Prevent any acute complications, initiate treatment for secondary prevention, ensure a comprehensive rehabilitation programme is established for each patient. Consider administration of medication for patients with symptoms of stroke e.g. dysphagia

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Summarise key concepts about cerebrovascular disease (3)

Enteral feeding tubes, alternative formulations (liquids). Compliance aids

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Cerebrovascular Disease

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