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Stroke - RCP London

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Stroke Tony Rudd Professor of Stroke Medicine Kings College London National Clinical Director for Stroke NHS England
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StrokeTony Rudd

Professor of Stroke Medicine Kings College London

National Clinical Director for Stroke NHS England

Predicted changes in Europe over next 20 years

The Burden of Stroke in Europe 2017

We know what a good stroke service should provide

Effective primary prevention

Public education about stroke symptoms and how to respond

Prehospital management ‘Diesel therapy’

Hyperacute stroke care for about first 72 hours

Acute stroke unit care for whole admission including in-patient rehabilitation

Early supported discharge

Longer term rehabilitation as needed

Vocational rehabilitation

Psychological support

Secondary prevention

Patient and carer support and education

Participation in research

Continuous quality improvement

Lecture outline

Putting hyperacute stroke care into context

Stroke unit evidence

Update on: IV thrombolysis

Thrombectomy

Intracerebral haemorrhage

What does acute stroke care offer?

Thrombolysis and thrombectomy are important treatments but must not forget the rest of the stroke population

For every 100 patients Up to 15% suitable for intravenous thrombolysis. Number needed to treat (NNT) for

one good outcome of 7. 2 patients benefit Up to 10% suitable for thrombectomy. NNT of between 2 and 7. 2 patients benefit About 30% will spontaneously recover with good basic medical care – 30 patients

benefit About 10% die in the first week – 10 patients

56 patients are left with disability and need on going treatmentDon’t devote all your efforts and resources to the 5% of patients who will

benefit from acute medical interventionsAnd remember 70% of all strokes could be prevented

Cochrane stroke unit review – patient subgroups

SUTC (2013)

Outcome - Death by end of scheduled follow up

Slide stolen from Peter Langhorne

Stroke unit outcomes - death or institutional care

.3 .5 1 2 5

1960

1970

1980

1990

2000

.3 .5 1 2 5

UK

Scandinavia

Mediterranean

China

Brazil

Australia/NA

High scanning rate

Low scanning rate

CT scanning rates

Stroke unit better Stroke unit better

Cumulative meta-analysis Regional results

Slide stolen from Peter Langhorne

What is a stroke unit?

• Coordinated multidisciplinary rehabilitation,

• Clear protocols for management of stroke related problems

• Staff with a specialist interest in stroke or rehabilitation,

• Routine involvement of carers in the rehabilitation process

• Regular programmes of education and training.

• Not just about acute stroke care

Association of care with good outcomesRCP stroke audit

“Stroke unit” item

Early stroke consultant assessment

CT scan within 24 hours

Early nurse & therapist assessment

Early swallow assessment & nutrition

management

Early iv fluids and aspirin

P value

0.009

0.49

0.028

<0.001

<0.001

0.5 0.75 1

Odds of death at 30 days

Bray et al BMJ (2013)

Adjusted Hazard Ratio of 30-day Mortality of Patients Admitted on Weekends, by Ratio of Registered Nurses Per Ten Beds on the Weekend

Bray BD, Ayis S, Campbell J, Cloud GC, et al. (2014) Associations between Stroke Mortality and Weekend Working by Stroke Specialist Physicians and Registered Nurses: Prospective Multicentre Cohort Study. PLoS Med 11(8): e1001705. doi:10.1371/journal.pmed.1001705http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001705

Higher mortality with fewer nurses

10

Time to SALT dysphagia assessment and risk of stroke-associated pneumonia

Modelled association adjusted for age, sex, stroke type (ischaemic, primary intracerebral haemorrhage, undetermined), pre-stroke functional level (modified Rankin Score), place of stroke (out of hospital or inpatient) and comorbidity, and NIHSS

Emberson J et al Lancet 2014; 384: 1929–35

Intravenous thrombolysis meta-analysis

Emberson J et al Lancet 2014; 384: 1929–35

Intravenous thrombolysis impact on mortality

Thrombolysing young patients

No patients under the age of 18 included in the RCTs of IV thrombolysis

SSNAP data: 230 patients under age of 30 thrombolysed – 43 under the age of 20 with 26 under 18 yrs.

Improvement in disability equivalent or better than for older patients

Age (years)

SIH (%)

Symptomatic intracranial haemorrhage rates

Meredith G et al Presentation at WSO 2018

How to communicate the risks and benefits: Patient guide to thrombolysis

Current state of thrombolysis

In UK about 12% of stroke patients receiving treatment (15% ischaemic patients)

Major limiting factors are time from stroke to arrival at hospital and strokes occurring in sleep

No clear advantage of low dose (0.6mg/kg) vs normal dose (0.9mg/kg)

Should be offered to appropriate patients up to 4.5 hours Can it be used for patients who present with wake up stroke and MRI imaging

suggesting no established infarction?

Is there an alternative to alteplase?

WAKE-UP trial: MRI guided thrombolysis for stroke of unknown time of onset

Patients with ischaemic lesion seen on DWI imaging but not on Flair suggesting likely to have occurred within last 4.5 hours

Excluded those suitable for thrombectomy

Stopped early because ran out of funding. 503 patients randomised (expected 800)

Thomalla G et al NEJM 2018;379:611-622

WAKE-UP Trial

Thomalla G et al NEJM 2018;379:611-622

EXTEND –IA TNK study

Tenecteplase vs alteplase 0.9mg/kg

Primary outcome reperfusion >50%; secondary outcome mRS at 90 days

202 patients recruited

Primary outcome achieved in 22% of tenecteplase patients and 10% alteplase patients

Median mRS 2 vs 3 in tenecteplase group OR 1.7; 95% CI 1.0-2.8 p=0.04

Campbell BCV et al NEJM 2018;378:1573-1582

Thrombectomy

80 year old man

History of AF, CCF, Pleural effusions (chest drain) DOAC recently stopped

11.00 am sudden onset of left sided weakness, neglect and homonymous hemianopia. NIHSS score 13

Brain imaging and CT angiography locally

1145 am: stroke team contacted

Transferred 13.00 am

13.15 am angio-suite

Procedure 13.30 am

Home next day with no deficit

Thrombectomy trial meta-analysis

Flynn et al, 2017

Goyal et al Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials Lancet 2016

•Goyal et al Endovascular

thrombectomy after large-vessel

ischaemic stroke: a meta-analysis of

individual patient data from five

randomised trials Lancet 2016OR: 2.49 (95% CI, 1.76 to 3.53; P<0.0001)

Thrombectomy trial results: Hermes meta-analysis

NNT to achieve mRS of 0-2 is 3.2-7.4NNT to shift by 1 mRSpoint 2.6

Appears to benefit those pre treated with tPA and those not given bridging therapy

107 patients in thrombectomy group and 99 in control26 centres over 30 months – each centre recruiting about 4

patients per year on average

Can we extend the treatment time? DAWN

study

DAWN Trial modified Rankin scores

Nogueira RG et al NEJM 2018:378;1:11-21

DEFUSE 3 Trial

6-16 hours after last known to be well with evidence of diffusion perfusion mismatch

Initial infarct size less than 70ml and ratio of volume of ischaemic tissue on perfusion imaging to infarct volume of 1.8 or more

Randomised to thrombectomy vs standard medical therapy

38 centres over 1 year

Terminated early with 182 patients for efficacy

About 5 pts per year/centre put into trial

Albers GW et al NEJM 2018;378:708-718

Thrombectomy trial at 6-16 hours using perfusion imaging: DEFUSE 3 Trial

Albers GW et al NEJM 2018;378:708-718

Time dependency of thrombectomy effect

Where are we with thrombectomy?

Currently treating about 1% of patients in England

Aiming to get to 10% in 5 years

Appropriate for patients with large anterior or middle cerebral artery occlusion up to 6 hours after onset of stroke

Still little RCT evidence for vertebro-basilar territory stroke

Using perfusion imaging maybe applicable to a small proportion of patients up to 24 hours after onset

Must be performed by teams with expertise – currently just interventional neuroradiologists in neuroscience centres

Does ‘time is brain’ apply to patients with intracerebral haemorrhage?

Significantly higher mortality associated with haemorrhage compared to infarction

Much less research into haemorrhage and fewer treatment interventions Surgery of limited benefit except where hydrocephalus and deteriorating

conscious level

High risk of early rebleeding

Demchuk et al Lancet Neurology 2012

Haematoma expansion leads to poor outcomes

30% of haemorrhages expand within the first 6 hours

Haematoma expansion

Controlling blood pressure INTERACT 2 trial

ATACH 2 trial

Reversal of anticoagulation

Using haemostatic agents?

Management of blood pressure after acute stroke. Two trials

Interact 2 ATACH-2

BP lowering to 140mm Hg systolic:

• Effective at reducing disability

• No effect on mortality

• No observed hazards

Interact 2 Trial results

ATACH-II trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage II)

If lower BP earlier and more intensively could this result in greater therapeutic benefit? Patients with GCS >5 and haematoma volume <60cm3

Used IV Nicardipine in incremental doses

ResultNo statistically significant benefit for lowering BP below 140mmHg

Haematoma expansion on anticoagulants

Reversal of anticoagulationin intracerebral haemorrhage

• Reverse INR to normal as quickly as possible for patient on warfarin using PCC and Vitamin K

• Idarucizumab for patients on dabigatran

• Other agents being developed for patients on DOACs (andexanetalpha)

Manchester project to improve processes of care after intracerebral haemorrhage

Parry Jones et al 2015 BMJ Qual Improv Rep 8

Summary

Major advances in acute stroke care in recent years

More to come Implementing what we know

Extending the use of reperfusion

Improved management of haemorrhage

Still many patients not benefiting from acute treatments

For those stroke units, longer term rehabilitation, better support adapting to disability needed


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