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