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StrokeWhat is it, What it’s not and

Role of the Stroke Pharmacist

Paresh ParmarLead Pharmacist

Stroke and Care of ElderlyNorthwick Park Hospitalpareshparmar@nhs.net

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Contents:

• Introduction

• What is a stroke? --Ischaemic & haemorrhagic Strokes

• Classification of stroke

• FAST-Time is brain-HASU and mobile units

• CT vs MRI

• Acute treatment of ischaemic stroke-aims

• Acute treatment of haemorrhagic stroke-aims

• Secondary prevention of stroke

• Stroke mimics (hemiplegic migraine, bells palsy, hypogylcaemia, brain tumors)

• Role of stroke pharmacist--Dysphagia, Aphasia, medication adherence, NMS/MUR referrals,

• Where to from here?

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A condition where a persons life changes within a second

affecting all facets of life

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Introduction:• Stroke accounts for 10% of all UK deaths (4th UK, 2nd world wide)• Stroke causes about 6% of deaths in men and 8% of deaths in women.• Every year in the UK, over 100,000 people have a stroke: 1 every 5 minutes• One in five strokes is fatal. Stroke mortality rates decreasing in UK.

• Stroke-related costs in the UK* approx. £9 billion - NHS £4.38 billion a year (49%) - Informal care £2.42 billion a year (27%).- Loss of productivity and disability £1.33 billion (15%) --Benefit payments total approximately £841m (9%)

• Surviving a stroke is frequently reported to be 'worse than death'

*Saka O, McGuire A, Wolfe C. (2009). Cost of stroke in the United Kingdom. Age and Ageing (2009) 38 (1): 27-32

Source: Stroke Association. State of the Nation: Stroke Statistics 2017

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What is a stroke - Classification

Classified as either ischaemic or Haemorrhagic:

• Ischemic stroke (85%)

• Haemorrhagic stroke (15%)

– Intracerebral haemorrhage(ICH)

– Subarachnoid haemorrhage (SAH-5%)

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Definition of TIA:

transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal

ischemia, without acute infarction lasting < 24 hrs

TIAs are often labeled "mini-strokes," or

"warning stroke" which is more appropriate for these temporary episodes, because they can

indicate the likelihood of a coming stroke.

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Definition of ischemic stroke:

An episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction

lasting > 24 hrs.

Sacco et al Stroke. 2013;44:2064-2089

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The risk of a recurrent stroke is highest early after an ischaemic stroke or transient ischaemic attack (TIA)—

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• The risk of recurrent stroke in survivors of acute stroke is about

-11·1% at 1 year,

-26·4% at 5 years,

-39·2% at 10 years.

J Neurol Neurosurg Psychiatry 2009; 80: 1012–18

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Definition of intracerebral haemorrhage (ICH):

A focal collection of blood within the brain parenchyma or ventricular system that is

not caused by trauma.

Haemorrhagic stroke has a higher mortality

rate than ischemic stroke*

Sacco et al Stroke. 2013;44:2064-2089

* American Heart Association. Circulation. 2014; 129(3): e28-e292

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Primary intracerebral haemorrhage Spontaneous ICH

Classified based on aetiology. SMASH-U: simple and practical classification.• S- Structural lesion (Cavernoma, AV-malformation)- 5%• M- Medication (Antiplatelet /Anticoagulants 14%, Alcohol, Cocaine, Amphetamine,

Nasal decongestants)• A – Amyloid angiopathy 20%• S- Systemic 5% (liver cirrhosis, thrombocytopenia )/Other• H-Hypertension 35%• U- Undetermined 21%

Patients with structural lesions have smallest haemorrhages and best prognosis.

Anticoagulation-related ICH were largest and most often fatal

Stroke. 2012 Oct;43(10):2592-7

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Aims of Intracerebral Haemorrhage (ICH) Management Hyper-acute unit

• BP Control (do not drop BP too quickly-hypoperfusion)

• Reversal of Anticoagulation

• Surgical Intervention

(hemicraniectomy)

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Stroke classifications

Stroke mechanism

• TOAST classification

Stroke territory

• OXFORD or BAMFORD

classification

Toast classification

Large-vessel disease

Small-vessel disease

Cardioembolism

Other aetiology

Undetermined or multiple possible aetiologies

Oxfordshire classification

S STROKE SYNDROME

IINFARCTION

H HAEMORRHAGE

Oxfordshire classification

• Total anterior circulationTAC

• Partial anterior circulationPAC

• Lacunar LAC

• Posterior circulationPOC

Oxfordshire classification

TACSTACI

TACH PACH

PACSPACI

LACS LACI

POCHLACH

POCS POCI

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TACS20%

PACS35%

LACS20%

POCS25%

% of strokes TACS-

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Right sided

PACS

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POCS

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LACS

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Stroke is a medical emergency

Prompt identification, diagnosis and treatment= decreases disability and decreases risk of mortality

TIME IS BRAIN

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The FAST testAims of Hyper-acute Ischemic Stroke:

Management :

• Thrombolysis

• Thrombectomy

• Secondary prevention :-Antiplatelet, -Blood pressure management, -Statins

• Role of stroke unit

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What happens in A&E?30 minutes to act

• Rapid assessment

– Ambulance team hand over

– History

– Examination

– BP and BM

• Urgent CT head

• If ischaemic stroke :To thrombolyse or Not to thrombolyse?

Door to needle time <30 minutes

CT scan

• Acutely, CT scan is to rule out a haemorrhage, in candidates potentially for thrombolysis

• scanning is quick and well tolerated. Acute haemorrhage is clearly visible in the acute phase as high attenuation. This appearance remains reliable for approximately 72 hours. By 10 days, haemorrhage becomes hypodense.

• In ischaemic stroke, a demarcated zone of hyperdensityappears, reflecting the arterial territory involved.

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CT Scan

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Thrombolysis

Alteplase (rt-PA) - within 4.5 hours is the first effective treatment for an ischaemicstroke for anterior circulation strokes

Benefits– at least 30 percent more likely to have minimal or no disability at three

months – 1.7 times more likely to have an improvement at 3 months

Risks– 4-8% significant hemorrhage– No increase in overall mortality– Risk dependent on stroke severity

Marler JR, et al. "Tissue Plasminogen Activator for Acute Ischemic Stroke". The New England Journal of Medicine. 1995. 333(24):1581-1587

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Who can get thrombolysis?

• <4.5 hrs onset with clear history of onset

• 18+ yrs

• GCS>8/15 (relative)

• Not on NOAC/Tx dose heparin or warfarin INR<1.7

• BP <185/110 mHg

• No recent surgery or bleeds

• Pregnant/breastfeeding

Alteplase IV : 0.9mg/kg, up to max dose of 90mg.

Prescribe 10% of dose as bolus over 2 mins, remaining 90% as infusion over 60 mins

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• Treatment response is time dependant.

• NNT is 7 for thrombolysis given within 3 hr. NNT doubles to 14 when given at 3 to 4.5 hrs.

Sooner a patient is thrombolysed, the better outcomes, thus door to needle <30min

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There are total 130 billion neurons in human brain.

With acute brain attack or vascular injury, approx. 1.9 million neurons are lost per second.

Every 4-minute delay in reperfusion, 1 out of 100 patients has increased 3-month disability.

Every 6- minute delay in reperfusion, 1 more out of 100 patients is functionally dependent at 3 months

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Acute thrombolysis BP management

• Intravenous formulations of short acting drugs should be used. There is no evidence to recommend one drug over the other.

• IV Labetalol and glyceryl trinitrate are the most commonly used in the UK.

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Thrombectomy

• Evidence only for anterior circulation strokes

• Within 6 hours of onset

• Over 18 yrs old

• Proximal thrombus

• NNT 3-7 (N Engl J Med. 2015;372:2285–2295)

Ciccone A, Valvassori L, Nichelatti M, et al; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013;368(10):904-913.Kidwell CS, Jahan R, Gornbein J, et al; MR RESCUE Investigators. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368(10):914-923.Broderick JP, Palesch YY, Demchuk AM, et al; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893-903.Berkhemer OA, Fransen PS, Beumer D, et al; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372(1):11-20.Goyal M, Demchuk AM, Menon BK, et al; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019-1030.Campbell BC, Mitchell PJ, Kleinig TJ, et al; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018.Saver JL, Goyal M, Bonafe A, et al; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015;372(24):2285-2295.Jovin TG, Chamorro A, Cobo E, et al; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296-2306

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Thrombectomy sites Middle cerebral Artery clots

String sign

Devices availablePENUMBRA

MERCI

Mobile units

Mobile stroke units (MSU)

• Germany/USA

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Mobile units

• Reduce the time taken for doctors to decide on the appropriate treatment by around 50%.

• Extremely expensive, at a cost of around £247,000 for the equipment alone.

• Option in rural/congested areas to reduce door to needle time for thrombolysis

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Equipped with:

• neuroimaging capabilities,

• point-of-care laboratory testing,

• telemedicine capabilities, and

• medications such as intravenous tissue plasminogen activator (IV tPA) and

• anticoagulant reversal capabilities.

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Stroke Risk Factors • About 80% of strokes are preventable

Modifiable Risk Factors Non-Modifiable Risk Factors

Hypertension Age

Atrial Fibrillation (↑ x5) Gender

Diabetes Family history of strokes

Hyperlipidaemia Ethnicity –Afro Caribbean ↑

Smoking (↑ x2) Genetics-e.g. Fabrys

Ischaemic heart disease Risk factors. Stroke 1997;28:1507.

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RCP UK guidelines 2016TIA

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Secondary prevention:Antiplatelets-RCP 2016

Statin-RCP guidelines 2016

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1 mmol/l reduction in cholesterol leads to 16 % risk reduction of stroke.

N Engl J Med 2006; 355: 549–59.

Secondary prevention: Hypertension

• Target is to lower BP to <130/80 after acute phase in ischemic stroke.

• 5mm Hg lower diastolic blood pressure (DBP) was associated with nearly one third fewer strokes.

• Reduction of 1 mmHg BP reduces risk of stroke by 3%.

• Which BP lowering agent? BHS guidelines

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Blood glucose 5 – 15 mmol/l

Diabetes and BM control- RCP guidance 2016

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Stroke causes a greater range of disabilities than any other condition*

49*Adamson J, Beswick A, Ebrahim S. (2004). Is Stroke the Most Common Cause of Disability? Journal of Stroke and Cerebrovascular Diseases. 2004 Jul-Aug;13(4):171-7

Common stroke mimics include:

• Bells Palsy -prednisolone 10/7,

– no evidence for antivirals*

• Hypoglycaemia (correct, symptoms disappear)

• Migraine aura (with or without headache-hemiplegic migraine)

• Focal seizure or post-ictal state (Todd’s paresis)

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*J Neurol Neurosurg Psychiatry 2015;86:1356–1361

• Brain tumours (stroke like symptoms)

• Subdural haematoma

• Metabolic disturbance

– (including hypoxia, drug overdose)

• Hypotension

– (hypoperfusion in brain can manifest as hemiparesis)

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• Determine how the patient swallowed food and medication prior to admission

• Review the patient’s• dysphagia treatment plan• medication

• Investigate alternative methods of administration, dosage forms, or drugs and make recommendations

• Document instructions on medication administration for the patient, family member or inpatient nurse and in patient record

• Transfer information to next sector of care

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Pharmacist’s role in supporting patients with dysphagia

Modified fluids and diet Where pharmacists commonly encounter solid and liquid medication, SLTs have classified fluid and food consistencies to meet patient’s swallowing needs e.g. Stage 1 fluids and puree texture.

This information can be used to support safe oral administration of medicines where simple liquid or solid medication may not be safe.

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Cover Story:Dysphagia and medicines: Ensuring patients with swallowing difficulties have the most efficacious formulationsAugust 2016, Vol 297, No 7892

Dysphagia

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Aphasia• Communication problems• Can be expressive or receptive or mixture of both• Liaise with SLT on how best to communicate with

patient• Use simple sentences• Yes/No questions • Speak slowly and clearly• Use pen and paper• Pictures• Transfer of care from secondary to primary-inform

community pharmacists how best to communicate

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Medication adherence • Assess patient’s disability: physical/cognitive

for medication administration

• Liaise with Carers/family for support

• MCAs, reminder charts, alarms, MARS chart

• Liaising with community pharmacist-MURS/NMS-increased pharmacist-patient concordance

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HASU Pharmacists presented at ESC London 2013

Results: 3.1 interventions per HASU patient56% was safety: either to prevent or in response to an adverse drug reaction or side effect,

25% was efficacy, to ensure optimal treatment for HASU patients,

13% to reduce the patients’ length of stay and expedite discharge

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Future therapies?

• Novel antiplatelets?

• tPA?

• Stems cells?

• anti-TNF –Etanercept?

• Monocloncal antibodies-GSK249320?

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Novel antiplatelets

• Ticagrelor (Socrates Trial)=patients with acute ischemic stroke or TIA, ticagrelor was not superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days, BUT

• Ticagrelor -superior to aspirin in strokes associated with ipsilateral atherosclerotic stenosis

The Lancet Neurology: Volume 16, No. 4, p301–310

Newer tissue plasminogen activators (tPA)

• Tenecteplase & Desmoteplase

– Currently unlicensed in stroke

– Longer half life and more potent than Alteplase

– More clinical trials underway

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Stem Cells

• Bone marrow mononuclear cells, hematopoietic stem cells, and multipotent adult progenitor cells –showing promise of neurorestorative effect after cerebral ischemia

• Clinical trials ongoing to further assess

-best dose,

-route,

-timing of this therapy

and to elucidate the efficacy of stem cell therapy in stroke

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Andrew Marr –Etanercept treatment

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American Academy of Neurology (AAN) practice advisory, “Etanercept for PoststrokeDisability,” which was published in Neurology ®

• cost of a 25-mg vial of etanercept is about $440 in USD

Neurology June 7, 2016 vol. 86 no. 23 2208-2211

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Monocloncal antibodies-GSK249320

• novel antibody-GSK249320, designed to inhibit destruction of the nerves involved in motor function after acute stroke

• Failed to show any improvement in motor function

• However, further clinical trials underwayStroke. 2017;48:00-00

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Driving and DVLA

• Single TIA –not drive for 1 month, no need to inform DVLA

• Multiple TIAs–not drive for 1 month, MUST inform DVLA

• STROKE:–not drive for 1 month, MUST inform DVLA

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Flying

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• No clear guidance

• Advised to contact airline

• General advice is wait 2 weeks post stroke before flying

• Also short haul vs long haul

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