steve phillips division of neurology - dalhousie university · % mild stroke 1 28 3 22 8 16 %...

When Not To Give TPA

Steve Phillips

Division of Neurology

[email protected]

Disclosures - 1

• AstraZeneca

• Boehringer Ingelheim

• Bristol-Myers Squibb

• Hoffmann-LaRoche

• Merck Frosst

• Pfizer

• sanofi-aventis

• Servier

I have given CME lectures and served

on advisory boards for

The QEII Acute Stroke Program has

received support from

GlaxoWellcome, Hoffmann-La Roche,

Merck Frosst, sanofi-aventis, Servier, Bayer

Disclosures - 2

• I was Canadian coordinator for the third

International Stroke Trial of t-PA (IST-3)

• I am a Clinical Advisor for Cardiovascular

Health Nova Scotia (CVHNS)

• I was inaugural co-chair of the Best

Practices & Standards Advisory Committee

of the Canadian Stroke Strategy

A broad spectrum treatment

IV t-PA works for

– mild, moderate, and severe strokes

– men and women

Stroke Thrombolysis Trialists’ Collaborative Group, 2014 & 2018

Treatment and outcomeBenefit

N / 1000 treated

IV tPA within 3 h of stroke^

- alive & independent months later 90

^Emberson J, et al. Lancet. 2014; 384: 1929-35


N / 1000 treated







N / 1000 treated





IV thrombolysis within 6 h of AMI*

- alive 35 days later30


*Fibrinolytic Therapy Trialists' Collaborative Group. Lancet. 1994; 343: 311-22

Odds Ratio

(95% CI)

1.0

Treatment delay (h)1.0 2.0 3.0 4.5

3.0

6.5

1.4

1.8

2.6

2.2

Effect of timing of IV t-PA

on good outcome (mRS 0-1)

Emberson, et al. Lancet 2014; 384: 1929-35

74 year-old woman

• 10:00 h sudden left arm weakness & slurred speech

• One month earlier had transient left leg weakness &

found to be in AF. Declined anticoagulant therapy

• Cognitively intact & functionally independent (CIFI)

• T+33 mins 911

• Pre-hospital Acute Stroke Protocol activation

• T+46 mins triaged into ED

74 year-old woman

• BP 190/100; AF on ECG

• Alert

• Dysarthric

• Visual fields full

• Left facial droop, arm paralyzed, leg drift

• No sensory loss or neglect

Diagnosis

• Localization:

• Syndrome:

• Severity:

• Mechanism:

• Prognosis:

Anterior right hemisphere

Partial MCA

Moderate (NIHSS=8)

Probable cardiogenic embolism

45% probability of death or

dependency at 1 year

Probable ischemic stroke

Multimodal CT imaging at T+90 mins

Andrew Demchuk, et al. Calgary Stroke Program

Stroke 2016; 47: 273-81

CT/CTA Head & Neck New Minimum Standard in Acute Stroke

• Accessibility

• Rapid acquisition

• Low risk

– low radiation exposure

– contrast–induced nephropathy 3%

– allergic reaction 1/10,000

Andrew Demchuk, et al. Calgary Stroke Program

Stroke 2016; 47: 273-81

Stroke type

TIA

AIS

ICH

Information acquired

cervical carotid stenosis

intracranial occlusion detection

collateral assessment

patho-anatomy of aortic arch

aneurysm & AVM detection

CT/CTA Head & Neck New Minimum Standard in Acute Stroke

5.1 Selection for Acute Ischemic Stroke

Treatments

Patients within 6 hours should immediately undergo NCCT

head + CTA head & neck to be considered for treatment.

[Evidence Level A]

Update 2018

Multimodal CT imaging at T+90 mins

Non-contrast CT head

Time-to-Peak

Cerebral Blood Flow

Cerebral Blood Volume

• Labetalol 10 mg IV x2 → BP 170/90

• PLT 250, INR 1.0

• Consent discussion; 7-10% bleeding risk

Consent issues

• Canadian Best Practice Recommendations 2018:

TPA is considered standard of care. Routine

procedures for emergency consent apply.

• US guidelines recommend obtaining informed consent

when feasible

• Obtaining consent delays treatment

“In cases of medical emergency when the patient (or

substitute decision maker) is unable to consent, a

physician has the duty to do what is immediately

necessary without consent.”

“… a contemporaneous record (at the time) should be

made explaining the circumstances which forced the

physician's hand.”

And

If you don’t treat, document why

and

explain to the patient’s family

ED physicians more often sued for not giving tPA for

stroke

Liang BA, Zivin JA. Empirical characteristics of litigation involving tissue plasminogen activator and

ischemic stroke. Ann Emerg Med. 2008; 52: 160-4.


• PLT 250, INR 1.0


• TPA started 2 h 20 m after stroke onset


• PLT 250, INR 1.0


• TPA started 2 h 20 m after stroke onset

• ~1 hour later: BP 180/100, mute, right gaze preference

NCCT 80 mins after start of t-PA

Patient deceased 7 hours after stroke onset

Predicting brain hemorrhage after t-PA

Karaszewski B, et al. J Neurol Neurosurg Psychiatry 2015; 86: 1127-36

• ↑age

• ↑BP

• ↑blood glucose

• ↑creatinine

• prior antiplatelets

• ↑stroke severity

• visible infarct on CT

• cerebral microbleeds

• very low cerebral blood

volume

first released December 2006 ● continuously updated since

5.3.i

•All eligible patients with disabling ischemic stroke should be offered IV t-PA.

•Eligible patients are those who can receive treatment within 4.5 hours of stroke onset.

[Evidence Level A]

Acute Ischemic Stroke Treatment. 2018 Update

5.3.ii

•All eligible patients should receive IV t-PA as soon as possible after hospital arrival.

[Evidence Level A]

•Target door-to-needle time <60 min in 90% of treated patients & median 30 min.

[Evidence Level B]

Acute Ischemic Stroke Treatment. 2018 Update

Update 2018

Thrombolytic Therapy

Inclusion Criteria

Age >18

<4.5 h since onset (or LSN)

Absolute Exclusion Criteria

Intracranial hemorrhage (ICH)

At ↑risk of major extracranial hemorrhage

Update 2018


Patients on a Direct Oral Anticoagulant

IV t-PA should not be routinely administered

In centers with access to specialized tests of DOAC levels and reversal agents, IV t-PA could

be considered…

Update 2018


Relative Exclusion Criteria

History of ICH

Stroke or head trauma in prior 3 months

Major surgery in prior 14 days

Arterial puncture in prior 7 days

Refractory hypertension >180/105

Enhanced Control of Hypertension and Thrombolysis

Stroke Study (ENCHANTED)

P: Ischemic stroke, <4.5 hours, SBP>140

I: 1. Intensive BP lowering (SBP 130-140)

2. tPA low dose (0.6 mg/kg)

C:1. Guideline BP lowering (SBP <180)

2. tPA normal dose

O: mRS

N: Target 4,800

PI: Craig Anderson, The George Institute for Global Health, Australia

www.strokecenter.org/trials

Update 2018


Relative Exclusion Criteria

Blood glucose <2.7 or >22.2

INR >1.7

↑PTT

PLT <100

ASPECTS <6

Alberta Stroke Program Early CT Score

Examine all the images at the ganglionic and supra-ganglionic levels

Take off 1 pt from 10 for every region affected

8-10 Small core6-7 Moderate core0-5 Large core

aspectsinstroke.com

Stroke Thrombolysis in Nova Scotia

Stroke Thrombolysis in Nova Scotia

2004/05* 2015^

Ischemic stroke patients 790 1150

Treated with t-PA 3% 13%

Arrived in time & treated 11% 40%

Median door-to-needle 93 min 68 min

*Provincial Stroke Audit

^CVHNS Provincial Stroke Registry

Bleeding Complications

sICH

Nova Scotia 2015 (n=183) 8%*

sICH=symptomatic intracranial hemorrhage

*CT confirmed or death within 48 h post-tPA

Bleeding Complications

sICH mECH

Nova Scotia 2015 (n=183) 8%

Systematic Review 2012 (n=3548) 8%

IST-3 (n=1515) 7% 1%

SITS Registry (n=6483) 7%

sICH=symptomatic intracranial hemorrhage; mECH=major extracranial hemorrhage

Update 2018


Treatment of Bleeding Complications

Insufficient evidence to support use of:

cryoprecipitate or fresh-frozen plasma

prothrombin complex concentrate

platelet transfusion

tranexamic acid

When Would I Not Treat?

• Very mild stroke causing

non-impairing deficit

• Very severe stroke in the

frail elderly or terminally ill

Insights from

1. Patients who arrive in time but are

not thrombolysed

2. Patients whose treatment is

complicated by brain hemorrhage

Data from QEII Acute Stroke Registry

Acute Ischemic Strokes Admitted Through QEII Emergency Department

2015 2016 2017 Total

N 257 264 225 746

TPA 73 (28%) 66 (25%) 52 (23%) 191 (26%)

Acute Ischemic Strokes Admitted Through QEII Emergency Department

2015 2016 2017 Total

N 257 264 225 746

TPA 73 (28%) 66 (25%) 52 (23%) 191 (26%)

Arrived <3.5 h

but no TPA

57 (22%) 51 (19%) 50 (22%) 158 (21%)

‘Lysed cf Not-’lysed (1/3)

2015 2016 2017

TPA No TPA TPA No TPA TPA No TPA

Age 75 79 69 76 75 80

% men 66 51 53 71 50 54

% living

at home

97 89 97 94 98 90

% living

alone

21 21 18 8 15 30


2015 2016 2017


Age 75 79 69 76 75 80

% men 66 51 53 71 50 54

% living

at home

97 89 97 94 98 90

% living

alone

21 21 18 8 15 30

Untreated patients older, less likely to be living at home


2015 2016 2017

% Prior: TPA No TPA TPA No TPA TPA No TPA

stroke 22 37 30 37 12 38

↓ cognition 10 30 14 25 21 38

dependency 10 25 11 27 19 30


2015 2016 2017

% Prior: TPA No TPA TPA No TPA TPA No TPA

stroke 22 37 30 37 12 38

↓ cognition 10 30 14 25 21 38

dependency 10 25 11 27 19 30

Untreated patients older, less likely to be living at home, and more

likely to have prior stroke, and cognitive and functional impairment


2015 2016 2017


% ASP activated 90 58 98 67 98 78

% Mild stroke 1 28 3 22 8 16

% Moderate stroke 64 42 59 63 58 66

% Severe stroke 34 30 38 14 35 18


2015 2016 2017


% ASP activated 90 58 98 67 98 78

% Mild stroke 1 28 3 22 8 16

% Moderate stroke 64 42 59 63 58 66

% Severe stroke 34 30 38 14 35 18

Untreated patients older; more likely to have prior stroke, cognitive and

functional impairment, and mild stroke; and less likely to be “code strokes”

Intracerebral hemorrhage after TPA at the HI

Intracerebral hemorrhage after TPA at the HI

2015 2016 2017 Total

TPA [no EVT] 62 52 40 154

ICH, n (%) 3 (4.8) 1 (1.9) 4 (10) 8 (5.2)

TPA [No EVT]

ICH No ICH

n=8 n=148

Age (median) 75 75

% men 40 60

% prior stroke 13 27

% prior ↓cognition 38 13

% prior dependency 25 13

Bleeders more likely to be women with prior cognitive impairment & functional dependency

TPA [No EVT]

ICH No ICH

n=8 n=148

LSN to TPA (median mins) 184 153

% AF 50 27

% mild stroke 0 5

% moderate stroke 63 68

% severe stroke 37 27

Bleeders more likely to be treated later, cognitively impaired, dependent, in AF

TPA [No EVT]

ICH No ICH

Stroke syndrome n=8 n=148

% MCA 75 74

% Lacunar 25 12

Bleeders more likely to cognitively impaired, dependent, in AF, with a lacunar stroke

TPA [No EVT]

ICH No ICH

n=8 n=148

% death in hospital 38 14

% survivors dependent at discharge 80 51

Last slide

• No useful clinical tool to predict who will bleed after t-PA

• Guidelines are helpful!

• Mild strokes are difficult!

• Frailty, comorbidity, impaired cognition, and functional dependency reasons not to treat

• There are worse things than dying from a severe stroke

steve phillips division of neurology - dalhousie university · % mild stroke 1 28 3 22 8 16 %...

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