The Specialist Forum Volume 13 No 11 November 2013 | Page 65

CPD ARTICLE

Impact of reperfusion therapy
for acute ischaemic stroke
Dr Johan Roos, Jamie Jooste, Dr Mark Abelson, Mediclinic Vergelegen, Western Cape

Abstract
Stroke remains a devastating disease. We believe the future of stroke
therapy will parallel the evolution of treatment of ST elevation myocardial
infarction, recognising that early reperfusion is critical to success.
In an era of older and newer reperfusion strategies applied in our stroke
unit we did a retrospective analysis of our data base of all stroke patients
admitted to the hospital from August 2011 – September 2012 (total of 196).

Introduction
The World Health Organization (WHO) estimates that each year 15 million people suffer strokes worldwide. Stroke claims the lives of 5.8 million
people and another five million are left permanently disabled annually.
Thrombolytic therapy for acute stroke was introduced in 1995 when the
results of the National Institute of Neurological Disorders and Stroke Study
with intravenous (IV) tissue plasminogen activator (tPA) were published.
The European Cooperative Acute Stroke Study III trial suggested that
extension up to 4.5 hours may also be safe and effective. A pooled analysis of eight major trials with tissue plasminogen activator (tPA) showed that
the net benefit of tPA disappears beyond 4.5 hours.
It often fails to achieve reperfusion (particularly in large vessel occlusions), and is associated with a significant bleeding risk. Several attempts
to develop thrombolytics with a better risk benefit profile than tPA failed.
Third generation thrombolytics like desmoteplase are more fibrin specific
with less neurotoxicity. Trials with this agent are still ongoing. The Efficacy
and Safety Study of Desmoteplase to Treat Acute Ischaemic Stroke 4
would also include subjects up to nine hours addressing the issue of what
to do with strokes out of the 4.5 hours time range. The recently published
results of the International Stroke Trial 3 for IV tPA up to six hours unfortunately turned out to be negative.
It became evident from analysing the National Institute of Neurological
Disorders and Stroke rt-PA Stroke Study that IV tPA was not effective in
large vessel stroke, which includes the internal carotid, proximal middle
cerebral, basilar and vertebral arteries. Strokes due to occlusion of these
arteries have a particularly high mortality and morbidity with very poor

A
B
C
Figure 1: A 66-year old female presents at six hours with dense right
hemiplegia and aphasia. NIHSS score = 23. A shows critical stenosis at
origin of right internal carotid artery (lateral view). Treated by gentle balloon angioplasty only. B shows complete occlusion of the distal internal
carotid where it bifurcates to anterior and middle cerebral arteries due to
embolism from the proximal carotid lesion (lateral view). C shows complete restoration of cerebral blood flow following embolectomy using the
Merci retriever (anterior view). The patient had a good recovery (MRS = 2).

Cardiology & Stroke Forum | November 2013

functional outcomes, especially if revascularisation could not be achieved.
In a meta-analysis of the impact of reperfusion on stroke outcomes,
successful recanalisation of the affected artery was by far the most important factor in improving stroke survival and functional outcomes (mortality
14.4% versus 41.6%, good outcome 58.1% versus 24.8% respectively).
The Merci Retrieval System was the first mechanical thromboembolectomy device developed for intracranial treatment of acute ischaemic
stroke. It was approved by the US Food and Drug Administration in August
2004 for patients who fail or who are ineligible for IV tPA.
The Multi-Merci study showed successful recanalisation occurred in
68%. In those patients successfully recanalised a good outcome (Modified
Rankin Score (MRS) at 90 days post-stroke ?2) was seen in 49% versus
9.9% in those where recanalisation failed. Mortality outcomes were 25%
versus 52% respectively.
New devices for mechanical embolectomy have become available
over the last couple of years; including the Solitaire (EV-3) and Trevo stent
retrievers and the Penumbra system. The stent retrievers are quicker and
technically easier to use with a significantly higher reperfusion rate (80+%)
and less haemorrhage.
The Swift Study comparing the Merci device to Solitaire in patients with
large strokes who had failed IV tPA or who were ineligible and was stopped
early as Solitaire was shown to be better. The Trevo 2 study also showed
superiority versus the Merci device with similar efficacy compared to the
Solitaire. Both these devices are currently available in SA.
In a study of 88 large ischaemic strokes due to acute middle cerebral artery occlusion patients received either IV tPA or, in those where IV tPA was
contra-indicated, embolectomy using the Solitaire device. Despite the fact
that those patients who underwent embolectomy had significantly larger
strokes (National Institute of Health and Stroke Scale [NIHSS] 14 versus 21)
and strokes were of longer duration (134min versus 234min), a favourable
clinical outcome (MRS ? 2) was seen significantly more frequently in the
embolectomy patients (60% versus 37.5% p<0.001).
Regarding diagnostic imaging in acute stroke, the Alberta Stroke
Programme Early Computed Tomography Score (Aspects) is an easy to
use modality to assess a patient’s suitability to receive reperfusion therapy.
Although the Aspects score has been criticised as being archaic and that
we should use the more modern imaging modalities (multi-modal computed tomography (CT), perfusion CT and CT angiography or diffusionweighted imaging-perfusion magnetic resonance imaging mismatch)
these imaging techniques are not always readily available, are more expensive and, of most importance, more time consuming -considering the
principal of time is brain.
Time to intervention post-stroke onset is an area of ongoing study.
Intravenous thrombolysis is of no benefit beyond 4.5 hours while intraarterial tPA was shown to be of some benefit up to six hours post-stroke
onset. Mechanical embolectomy studies have included patients up to
eight hours and occasionally beyond with good outcomes in appropriately
selected patients. In individuals with good collateral circulation, particularly
via the pial arteries, the ischaemic brain may remain viable, although nonfunctional, for up to 12 hours or more post stroke onset and these patients
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