Stroke Update Summary Sheet – Nov 2020

BP Target Goals
1. Hyperacute (FIRST 24 hours)
a. Intervention Group

Post TPA Post EVT

BP Targets BP < 180/105 for first TICI* 0 – 2A
24 hrs - SBP < 180
TICI 2B – 3
- SBP < 160
- Avoid large fluctuations in BP
Special comments No role for intensive BP
control to SBP 130-140
* TICI: Thrombolysis in Cerebral Infarction Scale

b. Non-intervention Group

HTN Emergency TIA Stroke

BP Targets BP < 220/110 Keep BP < 220/110 Keep BP < 220/110
Special comments Reduce BP by 10 – Can consider lowering BP gradually if
15% in first 24 hrs neurologically stable after 48-72 hours
(see table below)

2. Non-Hyperacute (>24hours)

Stroke Lacunar / SVD* ICAD ECAD AF

Subtypes
BP Targets BP < 130/80i BP < BP < 140/90 BP < 140/90
BP < 120/80ii 140/90iii,iv,v
Special RESPECT’s Unless bilat. 2018
comments intensive BP arm Significant carotid ESC/ESH
had reduced stenosis > 70% (aim guideline
stroke recurrence for higher BP) Class IIa
*SVD: Small vessel disease

a. Haemorrhagic Transformation
i. Aim SBP < 140 (extrapolated from spontaneous ICH trialsvi, AHA 2015
guidelines also suggest lowering SBP < 140, Class I, Level A)
ii. Also mindful of mechanism of stroke (i.e. if ICAD or large vessel occlusion, may
need slightly higher SBP targets to avoid worsening ischemic stroke penumbra)

3. Use of DAPT for minor strokes (NIHSS ≤ 3) or high-risk TIA (ABCD2 ≥ 4)

a. Data based on CHANCEvii trial, original protocol was to administer DAPT in intervention
arm within 24hrs of onset of symptoms
b. However sub-group analysis showed advantage of DAPT over SAPT in preventing
recurrent cerebral ischemic stroke, albeit limited to first 7- 10 days of treatmentviii.
c. May be reasonable to consider DAPT on a case-by-case basis

4. Mannitol Use in Large strokes

a. Use of osmotic therapy for patients with clinical deterioration from brain swelling
associated with cerebral infarction is reasonable. COR IIa, Level C evidence
5. Safety of Anti-platelet / Anti-coagulation after stroke with haemorrhagic transformation (HT)

Anti-Platelet Anti-Coagulation
Asymptomatic Haemorrhagic infarct HI) 1 / 2: Without HT:
HT - Can continue - 4 – 14 days after AISix (based
on RAF study)
Parenchymal Hematoma (PH) 1 / 2: Asymptomatic HT
- Should withhold - > 14 days
Symptomatic HT
- > 14 days (consider repeating
brain imaging prior to starting)
Special comments No guidelines regarding when No guidelines specifically when
suitable to restart suitable to restart, only consensus
based

Repeated brain imaging before starting

anticoagulation in patients with
moderate and severe stroke to evaluate
haemorrhagic transformation is
recommended only by the ESC
guidelines, without supporting
evidence.

Stroke Work up
Investigations:
1) Transthoracic Echocardiography – reasonable to exclude embolic cause and BEST to exclude
LV thrombus
2) Transcranial doppler with bubble – Sensitive to exclude right to left shunt, in particular PFO
3) Trans esophageal Echocardiography
a. If done for PFO there must be indication for PFO to be closed (Embolic stroke + age
<60 + no other indication for anticoagulation).
b. Can be done to exclude other causes of stroke – (infective endocarditis, atrial
myxoma, mitral valvular lesions, etc).
Prothrombotic work up
Suggest to test for Antiphospholipid syndrome for cryptogenic stroke. No indication to test for
inherited thrombophilia (Factor V, prothrombin mutation).
Predicting Cancer in Strokes
D-dimer level >3mg/L + multi-territory infarct increases the risk of Cancer in strokes. Reasonable to
screen for occult Ca in cryptogenic multi-territory embolic stroke.

Secondary Stroke Prevention - Grey areas

1) CYP2C19 testing
a) FDA black box warning: Clopidogrel may have reduced effectiveness for patients who are
CYP2C19 poor or intermediate metabolisers. Currently, guidelines do not specify that
CYP2C19 should be tested for all patients who are started on clopidogrel.
 b) However, if you do test the CYP2C19 status and the patient is found to be a poor or
intermediate metaboliser, it is reasonable to switch to aspirin (if aspirin naïve) OR
aspirin+dipyridamole (if failed aspirin monotherapy). If already failed aspirin or
aspirin+dipyridamole combination, then there is no good evidence at present to say what
alternative antiplatelet meds are better:
i) Ticagrelor is costly ($3/day) and has no long-term efficacy and safety data beyond 3
months
ii) Ticlopidine carries neutropenia risk and requires checking of FBC every 2 wks for first 3
mth
iii) No good evidence currently to support whether intermediate metabolisers will benefit
long term from clopidogrel or require higher doses of clopidogrel

2) Aspirin+Ticagrelor combination
a) Aspirin+Ticagrelor combination for first 30 days was superior to aspirin alone in reducing
disabling stroke or death in patients with TIAs and minor disabling strokes (NIHSS£5),
however there was a higher bleeding risk with this combination than with aspirin alone.
Whereas in the CHANCE study, the Aspirin+Clopidogrel group was superior to aspirin alone
for reducing the risk of stroke in the first 90 days but did not increase the risk of haemorrhage.

b) Ticagrelor is much more costly than clopidogrel

i) May be reasonable to consider using the aspirin+ticagrelor combination for first 30 days
in patients who are poor or intermediate metabolisers for clopidogrel (there is an ongoing
study CHANCE-2, which is studying this)
ii) Combination of ticagrelor and aspirin should only be used for 30 days, there is no
evidence to support longer term use of this combination

3) Microhemorrhages and anticoagulation

a) Increased risk of intracranial haemorrhage with 2 or more cerebral microbleeds, need to
balance this against risk of recurrent stroke for the individual patient
b) NOACs may be a safer option but no good data for this after the first year
c) Consider referring patients with microhaemorrhages to Cardiology for Left atrial appendage
closure using the Watchman device

4) Lipid control
a) Aim to lower LDL by 50% and <1.8mmol/L
b) LDL levels and liver function should be checked 4 to 12 weeks after starting statins and dose
adjusted to achieve target
c) Consider adding ezetimibe or refer to Endocrine for PCSK9 inhibitors (but this is very costly)
to achieve LDL target

i SPS3 Trial
ii Kitagawa et al. JAMA Neurol. 2019;76(11):1309-1318.
iii Turan et al. Relationship between risk factor control and vascular events in the SAMMPRIS trial. Neurology.

2017;88(4):379–85.
iv Turan et al. WASID. Relationship between blood pressure and stroke recurrence in patients with intracranial arterial

stenosis. Circulation. 2007;115(23):2969–75

v Powers et al. Lower stroke risk with lower blood pressure in hemodynamic cerebral ischemia. Neurology.

2014;82(12):1027–32
vi ATACH-2 (N Engl J Med 2016; 375:1033-1043); INTERACT-2 New England Journal of Medicine. 2015. 368(25):2355-2365
vii CHANCE trial, New England Journal of Medicine. 2013. 369(1):11-19.
viii Moussouttas M, Cerebrovasc Dis 2020;49:237–243, Pan et al. JAMA Neurol. 2019;76(12):1466-1473
ix RAF study, Stroke. 2015;46:2175-2182