Clinical Guidelines for Acute Stroke Management - Living on the EDge

4 ACUTE MEDICAL & SURGICAL MANAGEMENT
Section 4 as a whole was given a consumer rating of 10/10.
Section 4 <strong>Acute</strong> Medical & Surgical <strong>Management</strong>
4.1 Ischaemic stroke and TIA
4.1.1 Early management of TIA
<strong>Management</strong> of TIA involves early risk factor
management to prevent further ischaemic events.
An initial policy of commencing aspirin as soon as
haemorrhage has been excluded on CT or MRI is
recommended early after ischaemic event (see Section
4.1.3). While there is a lower long term risk of stroke in
those with TIA and AF compared to previous stroke
and AF 118 there is strong evidence <strong>for</strong> the long term
use of anticoagulation in patients with concomitant
AF. 118, 119 Other secondary prevention management
is the same as that outlined <strong>for</strong> those with stroke
(see Section 7).
4.1.2 Thrombolysis
Two systematic reviews have been undertaken
to determine the benefits of thrombolysis in acute
ischaemic stroke. 120, 121 Four different agents have
been evaluated: streptokinase, recombinant
pro-urokinase, recombinant tissue plasminogen
activator (rt-PA) and urokinase. Most of the data are
from trials of intravenous thrombolysis involving rt-PA.
Results found:
> Thrombolysis in all trials and all agents combined
results in a significant reduction in the composite
end-point of death or disability;
> Thrombolysis (all agents pooled) shows a net
benefit, but is associated with a definite risk of
intracerebral haemorrhage and increased mortality
at the end of 3 or 6 month follow-up.
> Heterogeneity between the trials was evident and
no clear evidence <strong>for</strong> one agent, dose or route was
found. There was indirect evidence that rt-PA may
have more benefit and less hazard.
> Therapy appears most beneficial if provided in
experienced centres in highly selected patients.
Widespread use of thrombolytic therapy in routine
clinical practice in non organised stroke care is not
recommended. 120
Subsequent pooled analysis from the rt-PA trials
confirm that treatment with intravenous rt-PA has a
clear net benefit in reducing the odds of death or
dependency if given within 3 hours. 122 Cases treated
within 3 hours showed 30% greater odds of functional
independence with a 12% absolute difference
between the rt-PA treatment group and placebo
treated patients (number needed to treat of
approximately 8). 122 Treatment given between 3-6
hours from stroke onset also appears promising and
further trials are underway (e.g. IST-3, ECASS-III).
Subsequent phase IV studies have generally
demonstrated similar outcomes to the major phase III
studies. 123 Protocol deviation has been identified
across one network of hospitals as a potential reason
<strong>for</strong> poorer clinical outcomes in routine practice as
compared to the outcomes obtained in the treatment
arms of the randomised trials. 124 However, an audit
and quality improvement process in these same
hospitals subsequently demonstrated a reduction in
protocol violations (50% down to 19.1% following the
quality improvement) and an associated decline in
adverse events from 15.7% to 6.4%. 125 Close
monitoring of outcomes, audit and quality
improvement activities are, there<strong>for</strong>e, strongly
recommended <strong>for</strong> all centres delivering rt-PA. The
international “Safe Implementation of Thrombolysis
in <strong>Stroke</strong>” (SITS) register is available to support data
collection, audit and benchmarking across centres
and across countries. Recent safety and clinical
outcome data from the European arm of the SITS
registry suggests lower adverse events than those
seen in the clinical trials of rt-PA. 126 Current Australian
data are comparable to the international data and are
shown in the table below.
OUTCOME AUSTRALIA* WORLDWIDE SITS PHASE III tPA DATA**
Independent at 3 months 51.4% 49.9% 50.1%
Symptomatic ICH 1.0% 1.7% 8.6%
Mortality 14.1% 13.9% 15%
Table 1. Safe Implementation of Thrombolysis in <strong>Stroke</strong> (SITS) register. Summary as of end of June 2007 * 393 total cases entered ** Phase III tPA data 122
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