Transcript No Slide Title

Mr X, 79 years old
Admitted on 5/5/00 to WGH stroke unit
Dense (0/5) right arm and leg paresis
Aphasic
CT scan excluded a bleed
Given trial treatment (IST-3)
Dramatic recovery 4-5/5 power, now talking
How does thrombolysis work?
Blood clots are a common cause of ischaemic stroke
They are made up of fibrin polymers cross linked by factor X111
(end result of intrinsic and extrinsic coagulation pathway)
Streptokinase
Plasminogen activators
PLASMINOGEN
FIBRIN
recombinant tissue-type plasminogen activator
PLASMIN
Fibrin degradation products
Thrombolysis for acute ischaemic
stroke
Not routine therapy in Edinburgh (or most of UK)
Why not?
To help you understand why not, I will:
•Present the world data on thrombolysis
•Compare the situation with myocardial infarction
•Explain why it could be too expensive to deliver
•What we are doing about it
Acute brain attack
Exclude: fits/migraine
Hypo-hyperglycaemia
Other metabolic causes
CT Scan
Exclude tumour
/structural lesion
Non-stroke pathology
Exclude:
intracranial
bleed
Confirmed ischaemic
brain attack
PICH, SAH,
Subdural
Confirmed ischaemic
brain attack
Are the symptoms/signs resolving rapidly?
Yes
TIA
No
Are the symptoms/signs disabling?
Yes
Consider more intensive treatment
No
Treat like
TIA
Thrombolysis: Acute Ischaemic Stroke
• Relatively short history - RCTs mid 80’s.
• Early decisions about agent and dose.
• NEJM 1995;333:1581-1587.
• rt-PA approved in North America for selected patients
within 3 hours of stroke onset. Not approved in Europe.
• rt-PA use remains quite limited.
? administrative & organisational barriers.
? evidence not as persuasive as for AMI.
Thrombolytic Time Window: Acute MI
• Systematic review of 9 large RCTs involving
58,000 patients.
Fibrinolytic Therapy Trialists’ Group. Lancet 1994;343:311-322
• Sufficient statistical power to provide reliable
estimates of:
DURATION of time window.
DECLINE in benefit over time.
Thrombolytic Time Window: Acute MI
Fibrinolytic Therapy Trialists’ Group. Lancet 1994;343:311-322
Data: Thrombolysis vs control
Thrombolytic
Agent
Number of Number of
RCTs
patients
IV tPA
IV SK
IV UK
IA Pro-UK
Total
8
4
3
2
2889 (56%)
1292 (25%)
743 (14%)
220 (5%)
17
5144*
*9% of available MI data;
data on 72 patients from ATLANTIS B not yet available.
Symptomatic ICH (fatal & non-fatal)
All trials:
– 2.5% control versus 9.5% treatment.
– 70 additional ICHs for every 1000 treated
(95% CI 58 - 83; 2p<0.000001)
rt-PA trials only:
– 3% control versus 10% treatment.
– 73 additional ICHs for every 1000 treated
(95% CI 55 - 90; 2p<0.000001)
No significant heterogeneity noted.
Dead or dependent at end of follow-up
• All trials:
– 59% control vs 55% treatment (2p=0.003).
– 44 more patients alive and independent for every
1000 patients treated (95% CI 15 - 73).
• rt-PA trials:
– 57% control vs 51% treatment (2p=0.002).
– 57 more patients alive and independent for every
1000 patients treated (95% CI 20 - 93).
• Significant heterogeneity noted...
Dead or dependent at follow-up:
randomisation within 3 hours
7 trials;
IV SK vs control
1168 patients
IV tPA vs control
NINDS
ECASS 1
ECASS 2
subtotal
IV SK+asp vs asp
TOTAL
0.1
0.58
thrombolysis better
1
10
thrombolysis worse
Absolute effect of thrombolysis for every 1000
patients treated: rt-PA
Outcome
0 - 6 hours
ICH
55 - 99 more
Dead
Dead or
dependent
7 fewer - 43 more
20 - 93 fewer
figures are 95% CI
0 - 3 hours
(data not available)
61 fewer - 38 more
77 - 203 fewer
Thrombolysis and living with
unproven treatments
Definite evidence of risk.
Evidence of benefit - but which patients benefit
most and which patients are most likely to be
harmed?
Answering this question may allow more
patients to be effectively treated with
increased certainty.
What remains unproven?
•
•
•
•
•
The upper age limit.
The latest time for effective treatment.
The role of aspirin.
The influence of stroke severity.
The influence of CT scan appearance.
• The generalisability of thrombolysis and the
organisation of acute stroke services in nonspecialist centres.
• Long-term effect of thrombolysis.
The Third International Stroke Trial
(IST-3)
Main features
•Streamlined trial (to encourage participation)
•Time window of <6 hours from onset (realistic and evidence based)
•Recruitment started in the Western General Hospital and six other
UK hospitals
Stroke IS an Emergency!

Stroke is a “Brain
Attack”

Stroke is an
emergency

“Time is Brain”
Future Stroke Treatment?
999
Within 3-6
Hrs?
Nurse led Stroke
Management
process Evaluation and
Triage
The Stroke Team
•
•
•
•
•
•
•
•
•
Ambulance Service
Casualty Dept & ICU/ASU
Radiology/Neuroradiology/
Physicians/Radiographers
Neurology & Neurosurgery
Pharmacy & Laboratory
Rehabilitation
Admissions
Administration
Public Relations/Community
Education