Update on Acute Stroke
Management and Recent
Important Clinical Trials
Dr Peter Anderton
Stroke Consultant
DBTH
Stroke Management • General, more magpie than systematic
• OXVASC data showed that atypical neurological symptoms not
meeting the NINDS TIA criteria nevertheless had a significant
long term stroke risk, and should hence be worked up and
treated fully.
– Transient confusion in the elderly is actually high risk for
future stroke: RR 10; we may need to broaden the
definition of what is a TIA (although I note that we should
acknowledge the differential and the possibility that this is
just fluctuant small vessel disease)
– DOUBT study also showed some surprising DWI + lesions
in patients thought less likely to have TIA (although all
patients were considered as at least possible TIA, perhaps
this is unsurprising)
• Centralisation
• Scanning
• Venous Stroke
ICH
• Salford ICH bundle – DNACPR
– DTN
– ICU
– Rapid BP lowering
• Praxabind (Idarucizumab) reverses Dabigatran
– 2 x 2.5g IV bolus within 5 minutes and consider repeat if
late rebound elevation in coag parameters
– Available in BDGH ED and DRI ED will now have it soon
• Xa inhibitors (Apixaban, Rivaroxaban, Edoxaban)
– Pending European approval/availability of Andexanet-a,
use:
– PPC at higher dose (30-50 IU/kg)
• Scope for a regional protocol to manage ICH
ICH: BP lowering
• Remains controversial
• INTERACT-2 did show improvement in a pre-specified subgroup analysis, and
this has driven the current RCP guidance target for acute BP lowering in ICH
• ATACH-2 showed no proven benefit for aggressive acute BP lowering, with an
excess of AKI (more aggressive than INTERACT-2
• BP lowering did not correlate with any change in haematoma expansion in
ATACH-2
• Data for DWI + lesions in ICH patients from ATACH-2 does not show a
correlation with BP lowering.
• Some post-hoc observational data from the Cleveland clinic showed more DWI +
lesions in stroke patients in 2014 than 2013, after they changed their BP target
from <160 to <140. However, the mean minimum BP in 2014 in such patients
was 102mmHg, suggesting to me that they overdid it and there may be a ceiling
effect to the benefit of acute BP lowering
• Thus, there is some evidence in favour of acute BP lowering, and there are no
new data to refute the current RCP guidance to lower BP to <140mmHg systolic
• Naturally we should avoid hypotension, which may have contributed to the higher
incidence of AKI in ATACH-2
tPA
• The RivLev assay can assess Rivaroxaban levels and may facilitate
thrombolysis in patients taking Rivaroxaban (perhaps they forgot it or
the levels are now low enough to treat)
– Median 34 mins to obtain result in Basel hospital setting
– Basel SOP:
o <20ng/ml rx
o 20-100 ng/ml consider rx
o >100 ng/ml don't give tPA, consider pure endovascular rx
• Consider the cost/feasibility of introducing this assay
Thrombectomy
• Thrombectomy is certainly coming
• Pooled analysis of trials by the VISTA collaborators
shows that endovascular treatment effect remains robust
even with the inclusion of earlier negative trials
• NHSE Commissioning Process 2017
• Limiting factor is trained staff
MR CLEAN
– 500 patients at 16 medical centers in the Netherlands
– 233 assigned to intraarterial treatment and 267 to usual
care alone
– The mean age was 65 years (range, 23 to 96)
– 445 patients (89.0%) were treated with intravenous
alteplase before randomization
– Retrievable stents were used in 190 of the 233 patients
(81.5%) assigned to intraarterial treatment.
– The adjusted common odds ratio was 1.67 (95%
confidence interval [CI], 1.21 to 2.30).
– There was an absolute difference of 13.5 percentage
points (95% CI, 5.9 to 21.2) in the rate of functional
independence (modified Rankin score, 0 to 2) in favor of
the intervention (32.6% vs. 19.1%)
– There were no significant differences in mortality or the
occurrence of symptomatic intracerebral hemorrhage.
Thrombectomy [2]
• Thrombectomy for wake up/late presenters is also on the
horizon - this will expand the numbers sent to thrombectomy
centre; might require MRI along with CTA or MRA (DAWN);
data from the TREVO registry showed improvement with
patients presenting up to 24 hrs with carotid or M1 occlusion
• Data from pooled analysis of ischaemic core analysis
endovascular trials show:
– age, ischaemia to reperfusion time and core volume are the key
prognostic variables
– even patients with large core make a significant improvement if
they re-perfuse
• Pooled analysis of endovasular trials shows that a 1 hr delay =
9.5% absolute reduction in the likelihood of a good outcome
• ?future stratification to direct immediately to thrombectomy
centre; initially ‘drip and ship’
Stroke: early management
• Swallow (SNS) +/- IV fluids
• VTE prevention
• Pyrexia / Infection
• Hydration/Nutrition/Pressure Care/Bowels / Bladder
• TALOS showed Citalopram is safe and possibly effective in
vascular prevention (trend) in non-depressed patients post
AIS but data from this trial do not conclusively show improved
function or reduced vacular risk; FLAME has previously
showed improved motor recovery with Fluoxetine 20mg od
post mod-severe hemiplegic ischaemic stroke.
• Arguably, based on FLAME, we should consider
Fluoxetine 20mg od in all appropriate patients on motor
grounds alone; this trial is certainly not contradicted by the
Citalopram data from TALOS
Antiplatelets
– Acute: TARDIS stopped early as neutral for vascular events but
excessive bleeding c triple therapy
– Chronic: SUCRA - Asa/Cl is best for prevention of recurrent
ischemia but also worst for bleeding complications; Asa/DP and
Clop are both reasonable for stroke prevention/bleeding risk
balance
– Asa good acutely
– Medium phase: potential role for asa+clopi; further trial results
awaited
– Chronic: clopi or asa/dp;
– ? Role for asa as potentially cancer preventing; if asa in elderly,
warrants PPI
– No reason to change from current RCP guidance at present
Malignant MCA Syndrome
Progression over 8 hours
thanks to
Aaron Phillips
Malignant Middle Cerebral Artery
Infarction
• Usually presents within 2-5 days of stroke
• Typically younger patients without
cerebral atrophy
• Mortality ~ 80%
• Compression of PCA
• Death from transtentorial herniation with
subsequent brain death
• Unproven medical/pharmacological
therapies
• Decompressive hemicraniectomy
Indications for Decompressive
Hemicraniectomy (NICE CG68)
• Age less than 60
• Signs suggest infarct in middle cerebral artery territory
• NIHSS score more than 15
• Decrease level of consciousness (giving a score of 1 or more on section 1a of NIHSS)
• Consistent CT head scan signs (at least 50% MCA territory +/- additional infarction in ipsilateral ACA or PCA territory)
or infarct volume >145cm3 on DW MRI
Vahedi K, Hofmeijer J, Juettler E et al.
Early decompressive surgery in malignant infarction of the
middle cerebral artery: a pooled analysis of three randomised
controlled trials.
Lancet Neurology 2007;6(3):215–222
Outcome Conservative % Surgery % OR (95% CI)
Mortality 71 22 0.10 (0.04-0.27)
mRS >4 76 26 0.10 (0.04-0.27)
age <50 years 71 23 0.10 (0.03-0.35)
age >50 years 91 31 0.13 (0.02-0.76)
Time to randomisation <24
hrs
81 31 0.12 (0.04-0.43)
Time to randomisation >24
hrs
69 18 0.13 (0.03-0.54)
No aphasia 82 22 0.06 (0.01-0.31)
Aphasia 74 29 0.14 (0.04-0.50)
BP
• Hypertension
• BP variability also predicts stroke risk, hence long acting
agents such as CCBs or diuretics may be of benefit
• ARBs good at reducing LVH and preventing AF/flutter;
also extremely well tolerated
• Maximum recorded BP even if not reflective of mean BP is
highly predictive of future stroke
• ABPI and home BP monitoring probably best; phenomenon
of masked hypertension
• How low to go? Not entirely clear, but note current guidance
and results of small vessel trial which benefited from a mean of
127 systolic, hence current gen prevention of <130/80
probably reasonable
• Qualitative research shows consistently (across cultures) that
patients attribute high BP to stress, and when the stress
goes away, they stop taking the pills and don't inform their
doctor: worth emphasising the need for ongoing rx
BP
• My approach
• Bradford
Questions?
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