Reperfusion therapy for Acute ischemic stroke Mloganzila Stroke Workshop presentation by Dr. Basil Tumaini

1. 1
Basil Tumaini, MD, MMed, MSc
Neurologist and Lecturer
Muhimbili University of Heath and Allied Sciences
Reperfusion therapies for acute
ischemic stroke

2. 2
CT scan CTA
IV rtPA
CTP
Preintervention
DSA
Postintervention
DSA
Endovascular
thrombectomy

3. 3
Introduction to Reperfusion Therapy
Definition
Restoring blood flow to the ischemic brain tissue
Goals
 Salvage the ischemic penumbra (area at risk)
 Minimize brain damage and improve outcomes
Mechanism of Action: restores cerebral perfusion
 Dissolves the clot
 Removes the clot

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Types of Reperfusion Therapy
1. Intravenous thrombolysis
Administration of thrombolytic drugs
2. Mechanical thrombectomy
Physical removal of the clot using endovascular
techniques

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Thrombolysis

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Mechanism of action of alteplase/tenecteplase
 Binding to fibrin
 Conversion of plasminogen to plasmin
 Clot dissolution
 Reperfusion of ischemic tissue
 Time sensitivity
 Potential risks

7. 7
Landmark thrombolysis trials
Trial
Name
Journal,
Year
Results Conclusion
NINDS
rtPA
NEJM,
1995
IV rtPA administered
within 3 hours of AIS
onset significantly
improved neurological
outcomes at 3 months,
with a 30% higher
likelihood of minimal or
no disability. There was
an increased risk of sICH
rtPA
administration
was associated
with 70%
increased odds
of functional
recovery at 90
days;
NNT=6

8. 8
Landmark thrombolysis trials
Trial
Name
Journal,
Year
Results Conclusion
ECASS
3
NEJM,
2008
Extended the rtPA
therapeutic window to
4.5 hours after stroke
onset. Patients treated
within this period had
significantly better
outcomes compared to
placebo, with a safety
profile similar to earlier
trials
↑42% functional
independence;
NNT=9

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DWI-FLAIR mismatch

10. 10
Landmark thrombolysis trials
Trial
Name
Journal,
Year
Results Conclusion
WAKE-
UP
NEJM,
2018
MRI-guided selection for
rtPA treatment in patients
with an unknown time of
stroke onset. Patients
with DWI-FLAIR
mismatch had better
functional outcomes at 90
days with rtPA compared
to placebo, with no
significant increase in
sICH
MRI-based
selection enables
safe and
effective rtPA
use in patients
with unknown
stroke onset,
especially for
wake-up strokes;
NNT=7

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Landmark thrombolysis trials
Trial
Name
Journal,
Year
Results Conclusion
TRACE
III
NEJM,
2024
Tenecteplase treatment
for ischemic stroke at 4.5
to 24 hours post-onset
resulted in a higher
percentage of patients
with minimal disability at
90 days compared to
standard medical
treatment
Tenecteplase
results in less
disability for
AIS patients
with LVO 4.5-24
hours when
thrombectomy is
not immediately
available, with a
higher risk of
sICH

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tPA eligibility
Class 1 of recommendation (Strongest)
Powers et al. Stroke 2019
Common
questions

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TPA ELIGIBILITY
Class 1 of recommendation (Strongest)
Powers et al. Stroke 2019

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Powers et al. Stroke 2019
Class III of recommendation

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Class III of recommendation
Powers et al. Stroke 2019

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Contraindications to rtPA
“SAMPLE STAGES” [absolute, relative]
• S Stroke (AIS) or head trauma - last 3 months,
SOL/intracranial neoplasm
• A Anticoagulation (on); INR>1.7, PT>15s,
aPTT>40s; DTL, DFXaI, GpIIb/IIIa I (last dose
within 48h); active internal bleeding, aortic
arch dissection, acute bleeding diathesis, arterial
puncture NCS in 7d
• M MI in prior 3months (recent)

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Contraindications to rtPA . .
P Prior ICH, evidence of hemorrhage on CTH;
pregnancy; intracranial vascular malformation; LMWH use
within 24hr for PE or DVT ℞
L Low platelet count <100,000/µL; large, untreated,
unruptured intracranial aneurysm
E Elevated BP: SBP ≥ 185, DBP ≥ 110 mm Hg
S Surgery, past 14 days; intracranial or spinal surgery,
past 3 months
T TIA, mild symptoms, rapid improvement
A Age < 18

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Contraindications to rtPA . . .
G GI/ urinary bleeding – past 14 days, malignancy,
infective endocarditis
E Elevated/ decreased blood glucose <50mg/dL
[2.7mmoL/L] or >400 mg/dL (22.2mmoL/L)
S Seizures at onset of stroke, SAH, extensive
regions of hypodensity on CTH consistent with
ischemic injury

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AcT trial
IV tenecteplase compared with alteplase for AIS in Canada
(AcT): a pragmatic, multicentre, open-label, registry-
linked, randomised, controlled, non-inferiority trial
 Tenecteplase is non-inferior to alteplase for achieving
functional independence at 90 days in patients with
AIS
 The safety profiles were similar, with no significant
differences in sICH or mortality between the two
groups
 Tenecteplase may offer a higher rate of early
recanalization compared to alteplase

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Mechanical thrombectomy

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Landmark thrombectomy trials;
NNT ~3-4
Trial
Name
Journal,
Year
Results Conclusion
MR
CLEAN
NEJM,
2015
Showed that intra-arterial
treatment significantly
improved functional
outcomes in patients with
AIS caused by proximal
intracranial arterial
occlusion
Mechanical
thrombectomy
within 6 hours of
stroke onset
significantly
increases the
likelihood of
functional
independence

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Landmark thrombectomy trials
Trial
Name
Journa
l, Year
Results Conclusion
EXTEND
-IA
NEJM,
2015
Demonstrated a
significant reduction in
infarct size and
improvement in
functional outcomes with
endovascular
thrombectomy plus tPA
compared to tPA alone
Endovascular
thrombectomy is
highly effective
in reducing
disability when
used in
conjunction with
intravenous tPA
in patients with
ischemic stroke

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Landmark thrombectomy trials
Trial
Name
Journal,
Year
Results Conclusion
SWIFT-
PRIME
NEJM,
2015
Showed that mechanical
thrombectomy using a
stent retriever
significantly improved
functional outcomes in
patients with ischemic
stroke who received
intravenous tPA
Combining
intravenous tPA
with mechanical
thrombectomy
results in better
functional
outcomes in
patients with
LVO

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Landmark thrombectomy trials
Trial
Name
Journal,
Year
Results Conclusion
REVAS
CAT
NEJM,
2015
Demonstrated a
significant improvement
in functional outcomes
for patients treated with
thrombectomy within 8
hours of symptom onset
compared to medical
therapy alone
Thrombectomy
within 8 hours of
symptom onset
is beneficial for
patients with
acute ischemic
stroke due to
LVO

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Landmark thrombectomy trials
Trial
Name
Journal
, Year
Results Conclusion
ESCAPE NEJM,
2015
Showed that
endovascular therapy
within 12 hours of
symptom onset
significantly improved
functional outcomes and
reduced mortality in
patients with ischemic
stroke
Early and rapid
endovascular
therapy provides
substantial
benefits in terms
of functional
independence
and survival

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Landmark thrombectomy trials
Trial
Name
Journal,
Year
Results Conclusion
DAWN NEJM,
2018
Demonstrated that
thrombectomy up to 24
hours after stroke onset
significantly improved
functional outcomes in
patients with a small
infarct core and large
clinical deficit
Mechanical
thrombectomy is
beneficial in
selected patients
with large vessel
occlusion stroke
even up to 24
hours after onset

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Landmark thrombectomy trials
Trial
Name
Journal
, Year
Results Conclusion
DEFUSE
3
NEJM,
2018
Showed that
thrombectomy 6 to 16
hours after stroke onset
significantly improved
functional outcomes in
patients with salvageable
brain tissue
Thrombectomy
is highly
effective when
performed 6 to
16 hours after
stroke onset in
patients with
mismatch
between clinical
deficit and
infarct size

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Landmark thrombectomy trials
Trial
Name
Journal
, Year
Results Conclusion
SELECT NEJM,
2018
Demonstrated that
thrombectomy in patients
with LVO and a
favorable imaging profile
improved outcomes
beyond the 6-hour
window
Favorable
outcomes can be
achieved with
thrombectomy
beyond the
traditional 6-
hour window in
patients selected
using advanced
imaging

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Landmark thrombectomy trials
Trial
Name
Journal
, Year
Results Conclusion
SELECT
2
NEJM,
2023
Showed that
thrombectomy in patients
with large infarcts
resulted in better
functional outcomes than
medical therapy alone
Thrombectomy
is beneficial
even in patients
with large
infarcts,
challenging
previous
exclusion
criteria based on
infarct size

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Landmark thrombectomy trials
Trial
Name
Journal,
Year
Results Conclusion
ANGEL-
ASPECT
NEJM,
2023
Demonstrated that
thrombectomy
improved outcomes in
patients with large
ischemic strokes
(ASPECTS ≤5),
expanding the
indication for
mechanical
thrombectomy
Thrombectomy
should be
considered in
patients with
large ischemic
strokes,
expanding the
eligibility for
this intervention

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Comparison: thrombolysis vs. thrombectomy
Indications:
 Thrombolysis: early treatment, smaller clots
 Thrombectomy: large vessel occlusions, extended
time window
Combination Therapy:
 Sometimes used together for optimal results

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Comparison: thrombolysis vs. thrombectomy
Success Rates:
 Thrombectomy: ~60-70% recanalization
 Thrombolysis: ~30% success in large vessels
Limitations:
 Thrombolysis: time-sensitive, risk of bleeding
 Thrombectomy: resource-intensive, not widely available

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Case Studies
Case 1: Successful Thrombolysis
 65-year-old male
 Onset of symptoms at 8 AM
 Administered tPA at 9:30 AM
 NIHSS score improved from 12 to 4 after treatment

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Case Studies . . .
Case 2: Mechanical Thrombectomy
 72-year-old female
 Found with stroke symptoms at 7 AM
 CTA showed large vessel occlusion
 Thrombectomy performed at 10 AM, NIHSS score
improved from 18 to 6

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Challenges and considerations
Delays in Treatment:
 Pre-hospital delays: recognition, transport
 In-hospital delays: imaging, decision-making
Access to Therapy:
 Limited availability of thrombectomy in low-resource
settings
 Disparities in healthcare access

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Challenges and considerations . . .
Managing Complications:
 Hemorrhage: intracerebral bleeding post-
thrombolysis
 Reperfusion injury: paradoxical worsening due to
restored blood flow

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DOs
 Always perform your own NIHSS
 Always confirm medications twice (patient/family and
pharmacy/bottles)
 Double check scans for hemorrhage before thrombolysis
 Obtain BP and glucose
 Go over all contraindications before giving tPA
 Get wake up MRI only if no LVO on CTA
Faddi Saleh Velez

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DON’Ts
 Give tPA unsafely in a rush
 Get a wake up MRI when you already have an LVO
(LVO goes straight to angiography if wake up stroke)
 Give tPA without BP control
Faddi Saleh Velez

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Conclusion
Summary
 Reperfusion therapy is crucial in AIS management
 Timely intervention can significantly improve
outcomes
 Both thrombolysis and thrombectomy have their
place in treatment

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Conclusion . . .
Call to Action
Emphasize the need for rapid stroke
recognition and treatment access

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Basil Tumaini, MD, MMed, MSc
Neurologist and Lecturer
Muhimbili University of Heath and Allied Sciences
Email: basil.tumaini@muhas.ac.tz
RG: Basil Tumaini
Reperfusion therapies for acute
ischemic stroke