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?