mr x, 79 years old admitted on 5/5/00 to wgh stroke unit dense (0/5) right arm and leg paresis...
TRANSCRIPT
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)
Plasminogen activators
Streptokinase
recombinant tissue-type plasminogen activator
PLASMINOGEN PLASMIN
FIBRIN 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 ScanExclude tumour /structural lesion Non-stroke pathology
Confirmed ischaemic brain attack
PICH, SAH, Subdural
Exclude:
intracranial bleed
Confirmed ischaemic brain attack
TIAAre the symptoms/signs resolving rapidly?Yes
No
Are the symptoms/signs disabling? No Treat like TIA
Yes
Consider more intensive treatment
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 controlThrombolytic Number of Number of Agent RCTs patients
IV tPA 8 2889 (56%)
IV SK 4 1292 (25%)
IV UK 3 743 (14%)
IA Pro-UK 2 220 (5%)
Total 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
IV SK vs control
IV tPA vs controlNINDS
ECASS 1ECASS 2 subtotal
IV SK+asp vs asp
TOTAL
0.1 0.58 1 10
thrombolysis better thrombolysis worse
7 trials;
1168 patients
Absolute effect of thrombolysis for every 1000 patients treated: rt-PA
Outcome 0 - 6 hours 0 - 3 hours
ICH 55 - 99 more (data not available)
Dead 7 fewer - 43 more 61 fewer - 38 more
Dead or 20 - 93 fewer 77 - 203 fewerdependent
figures are 95% CI
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 non-specialist 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
Nurse led Stroke Management
process - Evaluation and
Triage
Within 3-6 Hrs?
The Stroke Team
• Ambulance Service
• Casualty Dept & ICU/ASU
• Radiology/Neuroradiology/Physicians/Radiographers
• Neurology & Neurosurgery
• Pharmacy & Laboratory
• Rehabilitation
• Admissions
• Administration
• Public Relations/CommunityEducation
AMBULANCEAMBULANCE