CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 3, April 2013
88
AFRICA
the MCA only if given within six hours of stroke onset in patients
who are not otherwise candidates for IV r-tPA.
12
This would
include patients described in Table 1.
Prolyse in Acute Cerebral Thromboembolism (PROACT)
II, the only randomised study that has examined the safety and
efficacy of IA thrombolysis in patients with AIS, compared
outcomes of 121 patients in the treatment group treated with
intra-arterial recombinant prourokinase (r-proUK) and heparin
within six hours of stroke onset, with outcomes of 59 patients
in the control group treated with heparin alone.
21
In this study,
the technique involved placing an infusion microcatheter under
angiographic guidance into a proximally (M1 or M2 segment
of the middle cerebral artery) occluding thrombus; 4.5 mg of
r-proUK was infused at a rate of 30 ml/h into the thrombus.
One hour later, a second angiogram was done through the
microcatheter and the remaining 4.5 mg of r-proUK was infused
over the next hour. Another diagnostic carotid angiogram
was performed at two hours to assess final vessel patency.
Theoretically, IA thrombolysis may offer a higher dose of
thrombolytic drug delivery to the clot with fewer systemic
complications and higher recanalisation rates.
22
In the PROACT II treatment group, the recanalisation rate
was 66% with 40% of patients reaching functional independence
within 90 days.
21
In the control group, the recanalisation rate was
18% with 25% of patients reaching functional independence.
sICH occurred in 10% of treated patients compared to 2% of
controls, but the increase in sICH did not affect mortality rates,
which were 25 and 27%, respectively.
These results cannot be compared to any of the IV r-TPA
trials as the study methods and patient selections were different.
Also, one has to factor in the need for greater skill and the
risks of catheterisation when doing IA thrombolysis. There is
no randomised controlled study comparing IV r-TPA versus IA
r-TPA with/without heparin.
In a recent meta-analysis, the outcomes of IV r-tPA from
three randomised, controlled trials, namely, Middle Cerebral
Artery Embolism Local Fibrinolytic Intervention Trial (MELT),
PROACT and PROACT II were pooled together and statistically
averaged using odds ratios for 130 patients. This was then
compared to the outcomes of IA thrombolysis by sensitivity
analysis.
23
Using these statistical methods, no benefit was shown
from IA thrombolysis.
23
However the obvious criticism of this meta-analysis is that
data was obtained from three different trials in which the times
to treatment were not uniform. In the PROACT and PROACT II
studies, the authors could not obtain information of arrival time
to hospital and treatment with IV r-tPA.
Therefore while there is a suggestion in the literature that
IA thrombolysis is not significantly better than IV r-tPA, robust
studies using these two arms are still lacking.
23
Despite this the
results of this IA r-TPA trial were promising. Unfortunately,
treatment with prourokinase + heparin was not approved by
the FDA, which demanded a confirmatory study that was
never performed.
24
The availability of intra-arterial thrombolysis
should generally not preclude the intravenous administration of
r-tPA in otherwise eligible patients.
12
Clot removal
Mechanical clot retrieval
Mechanical revascularisation for acute stroke may be considered
in large-vessel occlusions. Recently, complex devices have been
developed. These can be divided into two major groups:
•
Proximal devices, which apply force to the proximal base of
the thrombus.
•
Distal devices, which approach the thrombus proximally but
a guide wire and microcatheter is advanced distally and then
unsheathed to apply force to the distal base of the throm-
bus. This group includes snare-like, basket-like or coil-like
devices.
Mechanical thrombectomy can also be performed in patients who
have received IV r-tPA and in those who are not candidates for
IV r-tPA. Results of multiple non-randomised trials have shown
these devices to be safe for clot removal in acute ischaemic
stroke patients presenting up to eight hours from onset of the
event.
22
It requires the knowledge and skills of trained neuro-
interventionalists with experience in the use of the devices. Two
FDA-approved devices are available specifically for mechanical
thrombectomy: the MERCI retriever and the penumbra system.
The Mechanical Embolus Removal in Cerebral Ischaemia
(MERCI) retriever is a cork-screw-shaped device consisting of a
flexible nitinol wire in five helical loops. It allows for placement
distally and then
en bloc
removal of the thrombus. The MERCI
and Multi MERCI trials evaluated the safety and efficacy in the
setting of stroke within eight hours of onset.
25,26
The MERCI trial included 151 patients with anterior or
posterior circulation stroke secondary to large-vessel occlusion.
25
Primary outcomes were recanalisation defined as a thrombolysis
in myocardial infarction (TIMI) score of 2–3 and safety.
25
Secondary outcomes were modified Rankin score (mRS) and
TABLE 1. USE OF IV THROMBOLYSIS INAIS
Indications for IV thrombolysis inAIS
• Age
>
18 and
<
80 years.
15
• Symptoms onset within 4.5 hours.
15
• Measurable deficit on the National Institutes of Health Stroke Scale
(NIHSS) examination.
4
• CT scan does not show haemorrhage or non-stroke cause of deficit.
4
Contraindications for IV thrombolysis inAIS
• Rapidly improving or minor symptoms.
12
• Stroke within past three months.
12
• Previous intracerebral haemorrhage or vascular malformation.
12
• Patient has symptoms suggestive of subarachnoid hemorrhage.
12
• Bleeding diathesis.
15
• Arterial puncture at non-compressible site or lumbar puncture within
the last seven days.
12
• Gastrointestinal or urinary tract bleeding in the last 21 days.
12
• Invasive surgery or delivery in last two weeks.
12
• Platelet count
<
100 000 /
µ
l.
12
• On treatment with heparin with prolonged aPTT.
12
• On treatment with oral anticoagulation with INR
>
1.7.
12
• Serious head trauma within the previous three months.
15
• Systolic blood pressure
>
185 mmHg, diastolic blood pressure
>
110
mmHg.
4
• No myocardial infarction in the previous three months.
12
• Seizures at onset of stroke with postictal residual neurological impair-
ments.
12
• Blood glucose
<
50 mg/dl (2.7 mmol/l).
4,15
• Multilobar infarction (hypodensity
>
1/3 of cerebral hemisphere).
12
