This document discusses the evolution of treatments for acute ischemic stroke caused by large vessel occlusion over the past three decades. It describes the development of intravenous thrombolysis using alteplase, including early safety trials, phase 3 efficacy trials, and limitations. It also discusses the emergence of endovascular therapies such as mechanical thrombectomy and the importance of neuroimaging such as CT and CT perfusion in selecting appropriate patients. The role of collateral circulation and a "tissue window" approach are also highlighted.

1. Revascularization in Acute Ischemic Stroke
Dr. N. Vinay Kumar
DM neurology resident

2. Introduction
• Ischemic stroke due to large artery occlusion (LAO)
predominates as a cause of disability, institutionalization, and
costs to healthcare and society.
• Therapies have changed the outcome of many patients with
acute ischemic stroke, preventing death and incapacity.

3. Evolution of Acute Ischemic Stroke (AIS) Care
• The past three decades have seen a revolution in the treatment of acute
ischemic stroke caused by large vessel occlusion (LVO).

4. In-hospital acute stroke pathway
Patient arrives without emergency
services team
Emergency department
Imaging(CT scan/MRI)
Eligible
for thrombolysis?
Triage nurse training
 Identification assessment
(FAST/ASA)
Notify ED doctor
 Stabilise patient
 Basic investigations, ECG and lab
tests
 Establish time of onset
 Severity assessment (NIHSS
score)
 Differential diagnosis
Notify stroke team (stroke call)
Request imaging
Referral to stroke unit
Stroke Unit
"TIME IS
BRAIN"
"TIME IS
BRAIN"

7. INTRAVENOUS THROMBOLYSIS

8. History of Thrombolytics
• The first thrombolytic activity was found by Tillet and Garner in 1933 in a
substance produced by group A beta-hemolytic streptococci.
• The substance was responsible for the clot dissolution was initially named
fibrinolysin, but the name was later changed to streptokinase .
• Fletcher et al. were the first to deliver IV streptokinase to human patients with
acute MI in 1958.
• During the 1980s, through recombinant technology, multiple second and third
generation lytics were developed.
• Second generation agent is alteplase (recombinant tissue plasminogen activator
[rt-PA]).
• Third generation thrombolytics Tenecteplase and reteplase had their chemical
structure slightly altered to increase fibrin specificity and to increase half-life.

9. Plasminogen activators
Endogenous:
• Tissue type plasminogen activator
(endothelial cells)
• Urokinase ( synthesized by renal and
malignant cells)
Novel :
• Microplasmin (recombinant form
microplasminogen)
Exogenous :
• Streptokinase (β hemolytic
streptococci)
• Anisoylated plasminogen
streptokinase activator complex
• Staphylokinase(from staphylococcus
aureus)
• Ancrod (venom from pit viper)

10. • Alteplase is a purified glycoprotein
• 527 amino acids
• synthesised from the complementary
DNA of natural human tissue-type
plasminogen activator found in
human melanoma cells.
• five structural components : a
protease, epidermal growth factor
(EGF) and two kringle domains
(Figure 3).
• The lysine binding sites of alteplase
are on the kringle 2 domain .

11. • Tenecteplase (TNK-tPA) is a third
generation point mutation tissue
plasminogen activator created by
recombinant DNA technology from a
mammalian cell line.
• 527 amino acid glycoprotein.
• Tenecteplase has modifications at
three sites of the protein structure on
the complementary DNA template
that differentiate TNK from Alteplase,
• substitution of threonine 103 with
asparagine
• substitution of asparagine 117 with
glutamine
• tetra-alanine substitution at amino
acids 296-299 in the protease domain

13. Thrombolysis for Cerebral Infarction: Early
Development
• Initial studies of thrombolysis in humans began in the late 1950s, but had
major limitations.
• Initial studies took place prior to the advent of computed tomography
(CT)
• Cerebrospinal fluid evaluation was performed to rule out hemorrhage.
• Medications initially tested were plasmin, strepto kinase, and urokinase.
• After the advent of CT in the 1980s, improved outcomes were noted in
urokinase- or streptokinase-treated patients.
• In1980s with the development of rt-PA pre clinical stroke evaluation using
an embolic model was performed by Zivin et al.
• Benefits seen with rt-PA were no anaphylactic-type reactions, no
antibodies were formed to rt-PA, complication of ICH less compared to
other thrombolytics.

14. Early Safety and Dose-Finding Trials in Stroke
• Phase I dose-escalation clinical trials using alteplase (rt-PA) were carried
out in the late 1980s in 2 parts: <90 minutes (74), 91 to 180 minutes(20)
• Doses of alteplase ranged from 0.35 to 1.08 mg/kg.
• Only 1 intracranial hematoma occurred among 64 patients received (1.5%)
who 0.85 mg/kg
• Higher doses 0.95 mg/kg were statistically associated with symptomatic
intracranial hemorrhages.
• Results of these 2 phase I studies led to the eventual 0.9 mg/kg alteplase
dose that is currently being used.
• del Zoppo et al. contributed important IV t-PA dose rate escalation
information in 139 patients who had recanalization monitored by a
conventional angiogram.

15. Review of Phase 3 Efficacy Trials
• Three major phase III clinical trials of alteplase were conducted in the 1990.
1) European Cooperative Acute Stroke Study (ECASS),
2) ECASS-II
3) National Institute of Neurological Disorder and Stroke (NINDS) rt- PA Stroke
trial

16. ECASS
• This study randomized 620 patients to placebo vs 1.1 mg/kg
alteplase within 6 h of symptom onset .
• More than 80% of the patients were enrolled within the 3- to
6-h window
• study did not reveal a significant difference between groups.

17. NINDS rt-PA study
• patients with a placebo vs 0.9 mg/kg of alteplase within 3 h of symptom onset.
• Half the patients treated with in 90 min.
• Study conducted in two parts.
• Part 1 was a phase 2b study of 291 patients having a primary endpoint 4-point
improvement of NIHSS at 24-h.
• part 2, a phase 3 study of 333 patients having a secondary endpoint of a 3-
month outcome.
• 4 different outcome measures (NIHSS, Barthel Index, modified Rankin scale
and the Glasgow outcome scale)
• greater rates of symptomatic intracerebral hemorrhage in alteplase group.
• Number needed to treat was 8 and the number needed to harm (causing a
symptomatic hemorrhage) was 17.
• Results of the NINDS trials led to 1996 Food and Drug Administration approval
of alteplase for acute ischemic stroke.

18. ECASS-II
• A second European trial studied the same t-PA dose (0.9 mg/kg) and
completed in 1998 .
• In contrast to the NINDS t-PA study, ECASS-II continued to study the 0 to
6-h treatment window.
• Again, the majority of patients were treated in the 3- to 6-h time frame
and no statistically significant difference was found between groups

19. ECASS-III and EPITHET
• The apparent treatment effect between 3- and 4.5-h was formally tested
in these studies.
• Total of 821
• NIHSS score was 9 in the t-PA group and 10 in the placebo
• More patients had a favorable outcome with alteplase than with placebo .
• The incidence of symptomatic intracerebral hemorrhage (sICH) was higher
with alteplase than with placebo (mortality did not differ).

20. IV TPA TRIALS
6 major randomized placebo controlled trials
 Alteplase Thrombolysis for Acute Non Interventional Therapy in Ischemic
stroke(ATLANTIS) I and II
 European Cooperative Acute Stroke Study(ECASS) I and II
 NINDS I and II
• 2775 Pts treated with IV rtPA or a placebo within 6hrs of onset
• Confined the benefit up to 3hrs
• ECASS III subsequently confirmed benefit of IV tPA in a 3 to 4.5hr window

23. Management of Blood Pressure in Ischemic stroke
• In acute ischemic stroke, parenteral antihypertensive medication should be
recommended only if there is a hypertensive emergency.
o hypertensive encephalopathy
o Malignant Hypertension
o hypertensive cardiac failure/myocardial infarction
o aortic dissection
o pre- eclampsia/eclampsia
Antihypertensive medication should be withheld in ischemic stroke patients unless
systolic blood pressure/diastolic blood pressure(SBP/DBP) >220/120 mmHg or the mean
arterial blood pressure (MAP) is >120mmHg. Lowering by 15% during the first 24 hours is
recommended.
Except in hypertensive emergency, lowering of blood pressure should be slow and with
use of oral medications.
Sublingual use of antihypertensive is not recommended.
Blood pressure reduction to 185/110 mmHg or lower should be considered in people who
are candidates for thrombolysis.

24. Pre-Thrombolysis
• If BP is >185/110 mm of Hg, Inj. labetolol 10-20mg I.V. should be given over 1-
2min and may be repeated every 10 min to a maximum dose of 300mg or
labetolol infusion can be started at 1 -8mg/min.
• If labetolol is not available, nitroglycerin infusion at 5μg/min or nicardipine
infusion at 5mg/hour is an alternative to labetolol.
• Aim is to continue treatment till target BP <185/110 mm Hg is achieved.
Post-Thrombolysis
• BP should be monitored every 15 min for 2 hours, then every 30min for next 6
hours and finally every hour for next 16 hours.
• BP goal is <180/105 mmHg.

25. Treatment after thrombolysis
• After thrombolysis, patients are admitted to the ICU or SU for monitoring.
• Close observation includes oral mucosa, puncture site, urine color,
traumatic site and vomiting.
• neurologic function assessments are performed every 15 min during and
after IVT therapy, and then once every 30 min for 6 h, once every hour
thereafter until 24 h after treatment .
• CT examination will be conducted at any time for patients with disease
changes.
• If NIHSS score more than four points at baseline is defined as hemorrhagic
transformation after thrombolysis, according to the amount of bleeding,
whether surgery is needed to do is immediately evaluated.
• if there is no indication for surgery, cold precipitation, platelets, plasma,
vitamin K1, tranexamic acid and other drugs can be used for symptomatic
treatment, and the patient’s vital signs and NIHSS score changes should be
closely monitored
• If there is no bleeding, anti-platelet aggregation drugs (aspirin 100 mg/day,
clopidogrel 75 mg/day) are given 24 h after surgery.

35. Sonothrombolysis
• Sonothrombolysis is a portable, inexpensive, and noninvasive tool for identifying
occlusions in patients with stroke.
• The adjuvant continuous ultrasound-based sonication of an intra-arterial occlusive
thrombus during thrombolysis, enhances the clot-dissolving capabilities of
intravenous thrombolysis, presumably by delivering mechanical pressure to the
surrounding fluids.
• Recently, some published trials examining the efficacy of ultrasound with standard
intravenous thrombolysis have shown that sonothrombolysis has beneficial effects
on recanalization and short-term outcomes in patients with acute ischemic stroke.

40. IV TPA- LIMITATIONS
• ICA and M1 occlusions have lower rate of recanalization than M2-M4
occlusions.
• 52% with NIHSS <10 will reach NIHSS of 1 after IV Tpa, but only 8% with
NIHSS>20
• 30% of MCA occlusions recanalize with IV Tpa only within 2 hours
• ICA occlusions recanalize only at 1/3 of the rate of MCA occlusions.

41. Logistic regression curve representing an estimate of the probability for
successful recanalization of occluded vessels by IVT depending on
thrombus length

42. Endovascular management
• Sussman and Fitch described the IA treatment of acute carotid occlusion
with fibrinolysin injection in 1958.
• Late 1990s experienced exponential progress and development.
• Early treatments with intra-arterial thrombolysis and insertion of
permanent stents and clot extraction devices, such as the Mechanical
Embolus Removal in Cerebral Ischaemia (MERCI) device, evolved into the
stent retriever devices used in most of the pivotal trials and, more
recently, aspiration devices.
• Recently, the concept of “tissue window” versus time window has proved
useful for selecting patients for mechanical thrombectomy up to 24 hours
from symptom onset

43. Ischemic penumbra :the area of brain tissue that is still viable but is critically
hypoperfused and will progress to infarct in the absence of timely reperfusion
• The paradigm of “time is brain” has been vital to strengthen the
importance of rapid treatment in acute stroke, several investigations have
demonstrated that other factors contribute to the degree of ischemic
injury at any point in time.

44. Areas of ischaemia following middle cerebral artery occlusion before (left)
and after (right) reperfusion

45. Regions of ischemia

46. Tissue vs. Time window
<3hrs
Early time is surrogate
marker for pneumbra
=
Imaging required
to assess
pathophysiology
>3hrs
Time from onset(hrs)
p
n
e
u
m
b
r
a

47. COLLATERAL CIRCULATION
• Survival of brain tissue supplied by an occluded or very stenotic artery
depends on
(1) the status of the obstruction (circulation may be restored either
spontaneously or by active treatment to dissolve or mechanically remove the
blockage);
(2) in case of partial occlusions, the ability of the systemic
circulation to adequately supply the ischemic region through augmented flow
either spontaneously or through therapeutic interventions such as induced
hypertension; and
(3) the presence and strength of collateral blood supply.

48. • Cerebral collaterals can be broadly divided into
1. the short bypass segments at the circle of Willis (primary collaterals)
2. the elongated leptomeningeal anastomotic routes able to deliver
retrograde perfusion to adjacent vascular territories (secondary
collaterals)
Each middle oval indicates
the potential connecting
vessels between the left and
right arteries in the
intracranial (A) and
extracranial-intracranial (B)
circulations.

49. NEUROIMAGING FOR SELECTING PATIENTS FOR ACUTE
ENDOVASCULAR THERAPIES
• An initial evaluation with a non contrast CT scan is necessary.
• Penumbra Pivotal Stroke Trial
1. Retrospective analysis of 85 patients
Results:
• Baseline CT scan by ASPECTS score >7 had a 50%chance of a favorable
clinical outcome with early recanalization
• ASPECTS scores <4 did not show clinical improvement regardless of
endovascular recanalization.

50. • Large territorial infarcts
High risk of hemorrhagic conversion
Poor candidates for endovascular therapy.
• Intra parenchymal hematoma is contraindication to endovascular
recanalisation
• Presence of a hyperdense MCA sign on the initial head CT does not have a
significant prognostic value in patient outcome and vessel recanalisation
rates.

51. CT PERFUSION SCANS
• Perfusion scan
demonstrates the
pneumbra lesion volume or
mean transit time which is
essential for determining
outcomes.

52. Angiographic evaluation
• To see for ischemic etiology and initiation of treatment.
• Based on the pt symptoms and pre procedure imaging,
selective catheterization of the carotid or vertebrobasilar
circulation supplying affected territory is performed.
• Grade of collaterals is a decisive factor for the degree of
reperfusion and clinical improvement.

53. REPERFUSION STRATERGIES
•Recanalization or antegrade reperfusion
•Global reperfusion(flow augmentation or transarterial
retrograde reperfusion)
•Transverse retrograde reperfusion (flow reversal)

54. Intraarterial chemical thrombolysis
• Agents converts plasminogen into plasmin degrades
fibrin and products.
• Recombinant tissue plasminogen activator(rtPA) and
recombinant urokinase have been widely studied and used
most frequently.
• Third generation agents such as reteplase and tenecteplase
have longer half lives(15-18 min) and favourable for
recanalization and lower recurrence rates.
• Half life of alteplase is 3.5min and urokinase is 7min.

55. • The aforementioned agents have prothrombotic effects by production of
thrombin during thrombolysis and subsequent activation of platelets and
fibrinogen.
• Concomitant use of systemic anticoagulation is recommended with
caution risk of ICH.
• Commonly used anti coagulant – heparin
Memon and colleagues study
Reviewed 35 cases of adjunctive use of eptifibatide in salvage reocclusion and
thrombolysis of distal thrombi with single bolus of 180µg/kg.
They reported a partial to complete recanalization of 77% with incidence of
post operative hemorrhage was 37%

56. Anterior circulation
• Middle cerebral artery
Three major clinical trials evaluated the efficacy of IA
thrombolysis in MCA circulation
1. PROACT I and II (Prolyse in Acute Cerebral
thromboembolism)
2. MELT trials(Middle Cerebral Artery Local Fibrinolytic
Intervention Trial)

57. PROACT1
• 40 patients were randomized for treatment of acute ischemic stroke
within 6hours of symptom onset
• Cerebral angiography was performed and M1 and M2 occlusions
were treated with 6mg of rpro-UK(n=26) or placebo|(n=14)
• Results: Rpro-UK treated patients had higher vessel recanalization
rates compared to placebo(57.7% vs14.3%). The incidence of ICH
was higher in rpro-UK group(15.4% vs 7.1%)

58. PROACT 2
• This randomized, controlled clinical trial treated pts with MCA
occlusion within 6hrs of symptom onset with either 9mg of IA
rpro-UK and heparin infusion(n=121) or heparin infusion
alone(n=59)
• Results: pts who received IA rpro –UK had significantly lower
Rankin scores at the 90 day endpoint compared to heparin
only treated pts.

59. Theron et al study
• Investigated the efficacy of IA thrombolysis in pts who
had acute ICA with MCA occlusion.
Results:
1. IA fibrinolysis of the MCA should be performed within
6hrs from ischemic onset, when occlusion involves the
horizontal segment of MCA extended into
lenticulostriate arteries.
2. If occlusion does not involve the horizontal MCA
segment and lenticulostriate arteries, then the
treatment window can extended to 12hrs following
symptoms.

60. Internal carotid artery
• Occlusions of extracranial ICA have better prognosis than intracranial ICA.
• Pts with insufficient collaterals or incomplete circle of willis may be
predisposed to significant neurological symptoms.
• Mechanical thrombolysis +pharmacological thrombolysis is of paramount
importance for recanalization.
• Flint et al published a series of 80 patients with ICA occlusion who were
treated with combinations of MERCI retriever with or without adjunctive
endovascular therapy. Recanalization rates were higher in the combination
group(63%) as opposed to MERCI group(53%)
• Arnold and colleagues presented a series of 24pts with distal ICA
occlusions treated with IA urokinase. Favourable 3 month functional
outcome was present in only 16%of pts and mortality rate was
approximately 42%

61. Posterior circulation
• Basilar artery occlusion is a life threatening event with untreated BA
occlusion having ,mortality rates ranging from 86% to 100%.
• In a series of nearly 300 patients, Furlan and Higashida reported an IA
recanalization rate of 60% and mortality rate 31%
• Lindsberg and matte compared BA occlusion treatment with IV or IA
thrombolysis.
• Results: recanalization rates were higher with IA treatment (65%vs 53%)
but death rates were equal between two groups.
• BASICS STUDY (Basilar Artery International Cooporation Study) 624 pts
with radiographically confirmed occlusion of the BA were enrolled in
nearly 50 centers over a 5yr period.
• Results: all pts treated with IA or IV thrombolytics beyond 9hrs from
symptom onset had a poor reported outcome.(therapeutic window 6-
9hrs)

62. Intraarterial mechanical thrombolysis
Broadly categorized into the following categories:
• Thrombectomy
• Thromboaspiration
• Thrombus disruption
• Augmented fibrinolysis
• Thrombus entrapment

63. Mechanical thrombectomy
• First generation:
 Merci Retriever(mechanical embolus removal in cerebral ischemia)
 Penumbra system devices
• Second generation:
 Solitaire flow restoration device
 Trevo retriever

65. Mechanical thrombectomy
a)Wire and catheter passed from femoral artery, over aortic arch, through ICA ,
to MCA and through the clot
b)Guide catheter removed and stent catheter advanced over the wire through
the clot
a b

66. c)Catheter pulled back, stent deployed into clot
d)Stent embedded in clot- traps the clot within device
mesh
c
d
Stent with embedded clot pulled back into guide catheter.

67. Endovascular thromboaspiration
• Aspiration technique which is suited for fresh non adhesive clots. These
devices also have advantage of fewer embolic material and decreased
vasospam.
• Penumbra stroke system is increasingly popular and uses 2 types of
devices to remove occlusive thromboembolus in acute ischemic stroke.
• Penumbra devices act on the proximal face of occlusion without traversing
the occluded artery.
• An aspiration device is used to debulk and extract the clot.
• A second retriever device resembling a stent attached to a guide wire is
used to remove resistant clot.

68. Mechanical thrombus disruption
• Mechanical disruption of clot is accomplished via a
microguidewire or a snare.
• Risks of vessel rupture and distal embolisation
• Some devices utilizing this mechanism are
EPAR(Endovascular,Belmont,California) and the LaTIS laser
device(LaTIS, Minneapolis,Minnesota)

69. Thrombus entrapment
• Utilizes a stent to recanalize the occluded vessel and therefore trap the
clot between the stent and vessel wall.
• Stents can be deployed via a balloon mechanism or could be self
expandable.
• Becoming popular due to their flexibility and ease of navigation

70. Solitaire and trevo
Stentriever
• Self expandable
• Retrievable
• Dual functionality:
 Acts as a temporary intracranial bypass providing immediate flow
restoration through the thrombus
 Acts as clot retriever, trapping thrombus into its cells allowing for clot
removal

71. RECANALIZATION SCORING

72. Evidence for mechanical
thrombectomy in 2013
• 3 randomized trials comparing IV-tPA to IA therapy published
in NEJM in 2013 found no difference in clinical outcomes:
 IMS II
 SYNTHESIS EXPANSION
 MR RESCUE

73. IMS III trial
• International RCT comparing
standard dose IV-rtPA and
mechanical thrombectomy.
• No pre procedure vascular
imaging was required before
enrolling pts for the study,
which led to 89 pts enrolled in
endovascular arm without
LVO.
• MERCI device was only FDA
appproved for the study.
• In 2012, study was stopped
due to futility and showing no
significant difference

74. SYNTHESIS trial
• Randomized pts into IV-
rtPA or endovascular
arms.
• Vascular imaging was not
mandatory to randomise
pts in endovascular arm.
• 2nd generation devices
were used in 13%pts
undergoing endovascular
treatment
• No functional benefit of
endovascular therapy was
observed (p=0.37)

75. MR RESCUE trial
• RCT of 1st generation
device MT in anterior
circulation in pts
randomized by MRI
perfusion imaging, in
addition to randomization
of embolectomy vs
medical therapy.
• There were no significant
differences between ,MT
and medical therapy
groups, regardless of
recanalization status.

76. Evidence for mechanical
thrombectomy in 2013

77. THROBECTOMY DEVICES

78. Recent advances in treatment
• Higher rates of successful recanalization
• Marked reduction in thrombectomy procedures times.
• Translates into improved outcomes

79. A Multicenter Randomized CLinical trial of Endovascular
treatment for Acute ischemic stroke in the Netherlands (MR
CLEAN)
• Sites: 16 centers in Netherlands
• Patients: 500
– 233 randomized to IA
thrombectomy
– 267 randomized to medical
management
• Age 18+
• Included mild-severe stroke
severity
• Time: Treatment initiated within
6 hrs
• Primary Outcome: mRS at 90 days
• Treatment in IA arm: No
requirement, but retrievable
stent in majority

80. A Multicenter Randomized CLinical trial of Endovascular
treatment for Acute ischemic stroke in the Netherlands (MR
CLEAN)
• Good Outcome (mRS 0-2):
– 33% in IA thrombectomy
group
– 19% in medical group
• Conclusion:
Significantly better
outcomes with
thrombectomy compared to
medical management

81. Endovascular Treatment for Small Core and Proximal Occlusion
Ischemic StrokE (ESCAPE)
• Sites: 22 centers mostly in N
America
• Patients: 315 (halted early due to
efficacy)
– 165 randomized to IA
thrombectomy
– 150 randomized to medical
• Age 18+
• Included mild-severe strokes
• Time: Treatment within 12 hours
of onset
• Primary Outcome: mRS at 90 days
• Treatment in IA arm: Retrievable
stent

82. Endovascular Treatment for Small Core and Proximal Occlusion
Ischemic StrokE (ESCAPE)
• Good Outcome (mRS 0-
2):
– 53% in IA thrombectomy
group
– 29% in medical group
• Conclusion:
Significantly better
outcomes with
thrombectomy
compared to medical
management

83. Solitaire With the Intention For Thrombectomy as PRIMary
Endovascular treatment (SWIFT PRIME)
• Sites: 39 centers mostly in US and
Europe
• Patients: 196 (halted early due to
efficacy)
– 98 randomized to IA
thrombectomy
– 98 randomized to medical
• Age 18-80
• Included moderate-severe strokes
• Time: Within 6 hours of onset and
within 1.5 hours of imaging
• Primary Outcome: mRS at 90 days
• Treatment in IA arm: retrievable
stent

84. Solitaire With the Intention For Thrombectomy as PRIMary
Endovascular treatment (SWIFT PRIME)
• Good Outcome (mRS 0-2):
– 60% in IA thrombectomy
group
– 35% in medical group
• Conclusion:
Significantly better
outcomes with
thrombectomy compared to
medical management

85. Endovascular Revascularization With Solitaire
Device Versus Best Medical Therapy in Anterior Circulation Stroke
Within 8 Hours (REVASCAT)
• Sites: 4 centers in Spain
• Patients: 206
– 103 randomized to IA
thrombectomy
– 103 randomized to medical
• Age 18-85
• Included mild-severe strokes
• Time: Within 8 hours of onset
• Primary Outcome: mRS at 90
days
• Treatment in IA arm:
retrievable stent

86. Endovascular Revascularization With Solitaire
Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8
Hours (REVASCAT)
• Good Outcome (mRS 0-2):
– 44% in IA thrombectomy
group
– 28% in medical group

87. The five most important published trials on
endovascular therapy in stroke

89. Candidates for Acute Endovascular Stroke Therapy
Inclusion criteria
• Age ≥18 years
• National Institutes of Health Stroke Scale score ≥6
• Time from symptom onset to groin puncture <6 hours (up to 24 hours if
evidence of sizable ischemic penumbra is seen on perfusion imaging)
• Good prestroke functional status
• Alberta Stroke Program Early CT Score ≥6 on baseline CT scan
• Presence of proximal intracranial artery occlusion
Exclusion criteria:
• BP>185/110mmHg
• Blood glucose <2.7 or >22.2mmol/L
• IV treatment with thrombolytic therapy in a dose >0.9mg/Kg
• Coagulation abnormalities(platelet count<40,000/ml or INR >3.0).

90. • The use of mechanical thrombectomy in patients with MCA M2 occlusions
within 6 hours from symptom onset may be reasonable for carefully
selected patients, as is its use in patients who have a prestroke modified
Rankin Scale score greater than 1, ASPECTS less than 6, or NIHSS score less
than 6.
• The benefit of mechanical thrombectomy in patients presenting within 6
hours from symptom onset and occlusion of the anterior cerebral arteries,
vertebral arteries, basilar artery, or posterior cerebral arteries remains
uncertain.
• It is important to highlight that, in all trials previously described, patients
received IV thrombolysis as a bridge to mechanical thrombectomy when
eligible and that the chances of better outcomes at 90 days within the
mechanical thrombectomy group declined with a longer time from
symptom onset to arterial puncture.
• Therefore, observation after IV thrombolysis to evaluate clinical
improvement before mechanical thrombectomy should not be performed.

91. complications
• Procedural complications
– Access-site problems
– Vessel/nerve injury
– Access-site haematoma
– Groin infection
– Device-related complications
– Vasospasm
– Arterial perforation and
dissection
– Device
detachment/misplacement
– Symptomatic intracerebral
haemorrhage
– Subarachnoid haemorrhage
– Embolisation to new or target
vessel territory
• Other complications
– Anaesthetic-related
complications
– Contrast-related complications
– Postoperative haemorrhage
– Extracranial haemorrhage
– Pseudoaneurysm

92. Conclusions
• Recent endovasculasar acute stroke trials have demonstrated
the superiority of combined treatment with MT and IV-rtPA
over medical therapy alone for pts with LVO who present
within 6hr.
• This is a revolutionary advance in ability to combat the
massive disability that results from stroke.

96. Thank you

97. References
• Jp mohr stroke pathophysiology, diagnosis, and management 5th edition.
• Zaheer Z, Robinson T, Mistri AK. Thrombolysis in acute ischaemic stroke: an update. Therapeutic
Advances in Chronic Disease. 2011;2(2):119-131. doi:10.1177/2040622310394032
• Tawil SE, Muir KW. Thrombolysis and thrombectomy for acute ischaemic stroke. Clin Med (Lond).
2017 Apr;17(2):161-165. doi: 10.7861/clinmedicine.17-2-161. PMID: 28365630; PMCID:
PMC6297620.
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