1. RECENT ADVANCES IN
THROMBOLYSIS IN A STROKE
PATIENT
GUIDE : DR. ARCHANA VERMA
CANDIDATE : DR. ADAMYA GUPTA

2. INTRODUCTION- STROKE STATISTICS
• Someone in USA has stroke once every 40 seconds
• Accounts for 1 in every 20 deaths in USA
• Stroke ranks no. 5 among all causes of death in USA.
• Second leading global cause of death behind heart disease.
INDIA
• Incidence- 105-152/lakh/year
• Prevalence – 3-5 fold increased.
South india- 57/lakh
North india- 44/lakh
• Stroke unit concept
Mortality drop from 58-36%

3. • 1.9 MILLION NEURONS
• 14 BILLION SYNAPSES
• 7.5 MILES MYELINATED FIBERS
In a Typical Acute Ischemic Stroke,
Every Minute Until Reperfusion the Brain Loses:
The sooner that rt-PA is given to stroke patients, the
greater the benefit, especially if started within 90
minutes of symptom onset

4. NIHSS Know the vocabulary

5. Acute Stroke Evaluation and Treatment:
60 Minute or Less Protocol
• Door to ED ≤ 10 minutes: Patient complaint, vital signs, ECG
• ED Physician ≤ 15 minutes: Focused history and physical exam, laboratories, stroke team activation,
transport for CT Scan (stroke protocol) Vital sign monitoring, neurologic checks, seizure and
aspiration precautions
• CT Scan and Stroke Neurology Consult ≤ 20 minutes: Review history, physical exam, interpret CT
Scan
• Treatment Decision and Initiate IV rt-PA infusion ≤15 minutes
10 + 15 + 20 + 15 = 60 minutes

6. BRAIN IMAGING
 All patients admitted to hospital with suspected acute stroke should receive brain imaging evaluation on arrival to
hospital. In most cases, non-contrast CT will provide the necessary information.
 For patients who otherwise meet criteria for EVT, a noninvasive intracranial vascular study is recommended
during the initial imaging evaluation of the acute stroke patient, but should not delay iv alteplase if indicated.
 For patients who otherwise meet criteria for EVT, with suspected intracranial large vessel occlusion (LVO) it is
reasonable to proceed with CTAngio (without S.creatinine)
 In patients who are potential candidates for EVT(mechanical thrombectomy), imaging of the extracranial carotid
and vertebral arteries is reasonable to do.
 In selected patients with AIS within 6 to 24 hours of last known normal who have LVO in the anterior circulation,
obtaining CTP, DW-MRI, or MRI PERFUSION is recommended to aid in patient selection for EVT
(mechanical thrombectomy)

7. Know the vocabulary
Thrombolysis In Cerebral Infarction Scale recanalization
outcome

8. ASPECT SCORE
http://www.aspectsinstroke.com
Know the vocabulary
 ALBERTA STROKE PROGRAM EARLY CT SCORE(ASPECTS)
IS 10 POINT QUANTITATIVE CT SCAN SCORE
 Aspects was developed to offer the reliability & utility
of a standard CT EXAM with reproducible grading
system to asses early ischemic changes on
pretreatment ct studies in patients with AIS of anterior
circulation.
 MCA Areas
 M1= Anterior MCA Cortex
 M2= MCA Cortex lateral to insular region
 M3= Posterior MCA Cortex
 M4= Anterior MCA Superior territory
 M5= Lateral MCA Superior territory
 M6= Posterior MCA Superior territory
 C = Caudate
 IC= Internal capsule
 I= Insular ribbon
 L= Lentiform nucleus
 1 point is subtracted from 10 for any evidence of early
ischemic changes in above mentioned areas

9. CLINICAL OUTCOME MEASURE / FUNCTIONAL INDEPENDENCE
Modified Rankin Score (MRS)
0
No symptoms at all
1
No significant disability despite symptoms; able to carry out all usual duties and activities
2
Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
3
Moderate disability; requiring some help, but able to walk without assistance
4
Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without
assistance
5
Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6 Dead
Know the vocabulary

11. Other Diagnostic Tests
Only the assessment of blood glucose must precede the initiation of IV alteplase in all patients.
Baseline ECG assessment is recommended in patients presenting with AIS, but should not delay
initiation of IV alteplase.
Baseline troponin assessment is recommended in patients presenting with AIS, but should not delay
initiation of IV alteplase.
Usefulness of CXR in the hyper-acute stroke setting in the absence of evidence of acute pulmonary,
cardiac, or pulmonary vascular disease is unclear.
NOTE: If obtained, they should not unnecessarily delay administration of IV alteplase. (Class IIb; LOE B-NR)

12. I/V FIBRINOLYSIS
• RTPA
• INCLUSION AND EXCLUSION CRITERIA(WITHIN
3 HRS)
• ADDITIONAL CRITERIA (3-4.5 HRS)
• RECOMMENDATIONS
• TRIALS

13. BLOOD PRESSURE
• Hypotension and hypovolemia should be corrected to maintain systemic perfusion levels necessary to support
organ function.
• In patients with BP ≥220/120 mmHg who did not receive IV alteplase or EVT and have no comorbid
conditions requiring acute antihypertensive treatment, the benefit of initiating or reinitiating treatment of
hypertension within the first 48 to 72 hours is uncertain. It might be reasonable to lower BP by 15% during the
first 24 hours after onset of stroke.
• Patients who have elevated BP and are otherwise eligible for treatment with IV alteplase should have their BP
carefully lowered so that their BP is <185/110mmHg before IV fibrinolytic therapy is initiated.
• Evidence indicates that persistent in-hospital hyperglycemia during the first 24 hours after AIS is associated with
worse outcomes than normo-glycemia and thus, it is reasonable to treat hyperglycemia to achieve blood glucose
levels in a range of 140 to 180 mg/dL and to closely monitor to prevent hypoglycemia in patients with AIS.
• Hypoglycemia (blood glucose <60 mg/dL) should be treated in patients with AIS.

14. PRIOR ANTIPLATELET THERAPY
• IV alteplase is recommended for patients taking antiplatelet drug monotherapy before stroke on the
basis of evidence that the benefit of alteplase outweighs a possible small increased risk of s-ICH.
• IV alteplase is recommended for patients taking antiplatelet drug combination therapy (eg, aspirin
and clopidogrel) before stroke on the basis of evidence that the benefit of alteplase outweighs a
probable increased risk of s-ICH.
 In patients with end-stage renal disease on hemodialysis and normal aPTT, IV alteplase is recommended.
(Class I; LOE C-LD)

15. Ref: Bradley’s
Neurology

16. Ref: Bradley’s
Neurology

17. Ref: Bradley’s
Neurology

18. Ref: Bradley’s
Neurology

19. RECOMMENDATIONS
1) INTRAVENOUS RTPA (0.9 MG/KG, MAXIMUM DOSE 90 MG) IS RECOMMENDED FOR
ADMINISTRATION TO ELIGIBLE PATIENTS WHO CAN BE TREATED IN THE TIME PERIOD OF 3
TO 4.5 HOURS AFTER STROKE ONSET (CLASS I) WITH THE ADDITIONAL EXCLUSION CRITERIA.
2) PHYSICIANS SHOULD BE AWARE OF AND PREPARED TO EMERGENTLY TREAT POTENTIAL
SIDE EFFECTS, INCLUDING BLEEDING COMPLICATIONS AND ANGIOEDEMA THAT MAY
CAUSE PARTIAL AIRWAY OBSTRUCTION (CLASS I)
3) INTRAVENOUS RTPA IS REASONABLE IN PATIENTS WITH A SEIZURE AT THE TIME OF ONSET
OF STROKE IF EVIDENCE SUGGESTS THAT RESIDUAL IMPAIRMENTS ARE SECONDARY TO
STROKE AND NOT A POSTICTAL PHENOMENON (CLASS IIA)
4) THE EFFECTIVENESS OF SONOTHROMBOLYSIS FOR TREATMENT OF PATIENTS WITH ACUTE
STROKE IS NOT WELL ESTABLISHED(CLASS IIB)

20. RECOMMENDATIONS
5) THE USEFULNESS OF INTRAVENOUS ADMINISTRATION OF RETEPLASE, DESMOTEPLASE,
UROKINASE, OR OTHER FIBRINOLYTIC AGENTS AND THE INTRAVENOUS ADMINISTRATION
OF ANCROD OR OTHER DEFIBRINOGENATING AGENTS IS NOT WELL ESTABLISHED, AND
THEY SHOULD ONLY BE USED IN THE SETTING OF A CLINICAL TRIAL(CLASS IIB)
6) THE INTRAVENOUS ADMINISTRATION OF STREPTOKINASE FOR TREATMENT OF STROKE IS
NOT RECOMMENDED (CLASS III).
7) THE USE OF INTRAVENOUS RTPA IN PATIENTS TAKING DIRECT THROMBIN INHIBITORS OR
DIRECT FACTOR XA INHIBITORS MAY BE HARMFUL AND IS NOT RECOMMENDED UNLESS
SENSITIVE LABORATORY TESTS SUCH AS APTT, INR, PLATELET COUNT, AND ECT, TT, OR
APPROPRIATE DIRECT FACTOR XA ACTIVITY ASSAYS ARE NORMAL, OR THE PATIENT HAS
NOT RECEIVED A DOSE OF THESE AGENTS FOR >2 DAYS .

21.  Administration of aspirin is recommended in patients with AIS within 24 to 48 hours after onset.
 For those treated with IV alteplase, aspirin administration is generally delayed until 24 hours later
 In patients presenting with minor stroke, treatment for 21 days with dual antiplatelet therapy (aspirin
and clopidogrel) begun within 24 hours can be beneficial for early secondary stroke prevention for a
period of up to 90 days from symptom onset. (Class IIa; LOE B-R)
ANTIPLATELETS
Urgent anticoagulation, with the goal of preventing early recurrent stroke, halting neurological
worsening, or improving outcomes after AIS, is not recommendedfor treatment of patients with AIS.
ANTICOAGULANTS

22. Head CT
Stroke Symptoms < 3 hrs from
time Last Known Normal (LKN)
Acute Ischemic Stroke
Go to IV tPA protocol -
Eligible for IV tPA?
Give IV tPA
Ye
s
No
Admit
ACUTE ISCHEMIC STROKE DECISION-MAKING
1998
NINDS IV
tPA

23. Head CT
Stroke Symptoms < 4.5 hrs from time Last Known Normal
(LKN)
Acute Ischemic
Stroke
Go to IV tPA protocol -
Eligible for IV tPA?
Give IV tPA
Yes
No
Admit
ACUTE ISCHEMIC STROKE DECISION-MAKING
2008
ECASS III

24. Stroke Symptoms < 24 hrs from time Last Known
Normal (LKN) and Head CT without ICH
Acute Ischemic Stroke Stroke Mimic
Go to IV tPA protocol: LKN < 4.5 hr
and eligible for IV tPA?
Go to HyperAcute MRI
Protocol; DWI c/w AIS?
Mimic vs. AIS
Give IV tPA
NIHSS ≥ 6 and LKN <16 hr or
NIHSS ≥ 10 and LKN 16-24 hr?
Triage per
Prelim. Dx
No
Yes
No (and has not
received tPA)
Yes
Yes
Bridge to
Endovascular
Wake-up / Unwitnessed stroke
> 4.5 hr from LKN, can get
hMRI and be treated with IV
tPA < 4.5 hr from sx discovery?
No
Go to Wake-up /
Unwitnessed
Onset hMRI Stroke
Protocol
Perform RAPID / CTA. Go to Endovascular Protocol: Is
LVO present and eligible for thrombectomy?
No
Yes
Thrombectomy
Yes
2018

25. EVOLUTION OF ACUTE ISCHEMIC STROKE (AIS) CARE OVER TWO DECADES
NINDS IV TPA
ALTEPLASE 0-3
HRS
ECASS I
Alteplase 0-
6hr
ATLANTIS
Alteplase 3-5
hrs
1995 1998
1996
2008
ECASS-3
Alteplase 3-
4.5hr
PRISMS
Alteplase 0-
3hr Non-
Disabling
EXTEND-IA TNK
Tenectoplase 0-
6hr CTP-
selected + LVO
2018
201
7
NOR-TEST
Tenecteplase
0-4.5hr
EPITHET
Alteplase 3-
6hr MRI-
selected
ECASS II
Alteplase 3-6
hrs
2009
MR-WITNESS
Alteplase 4.5-
24hr MRI-
selected
IMS III, MR
RESCUE,
SYNTHESIS
Endovascular
Early Devices
< 5-8hr
Tenecteplase
vs. Alteplase
0-4.5hr CTP-
selected + LVO
2012
DIAS / DEDAS
Desmoteplase 3-
9hrs MRI-selected
2005-2006
WAKE-UP
Alteplase >
4.5hr MRI-
selected
DEFUSE Alteplase
3-6hrs MRI-
selected
ASK
Streptokinase
0-4 hrs
MR CLEAN, ESCAPE, EXTEND-
IA, SWIFT-PRIME, REVASCAT
Endovascular New Devices <
6-12hr
DAWN, DEFUSE 3
Endovascular 4.5-
24hr CTA-CTP
selected
DIAS-2
Desmoteplase 3-
9hrs MRI-
selected
2015
2013
2015
< 24 hr< 4.5 hr

26. ACUTE STROKE MANAGEMENT HAS EVOLVED
OVER TIME
• IV TPA <3HRS (1998)
• EXTENDING TIME WINDOW TO 4.5HRS (2008)
• SUCCESSFUL INTRAARTERIAL THERAPY TRIALS (2015).
• ENDOVASCULAR THERAPY WITHIN 4.5-24HRS CT ANGIO-CT PERFUSION
MISMATCH SELECTED (DAWN, DEFUSE 3 2018)
• ALTEPLASE > 4.5HR MRI-SELECTED (WAKE-UP 2018)
• TENECTEPLASE 0-6HR CTP-SELECTED + LVO (EXTEND-IA TNK 2018)

27. Conclusion of various trials:
Over a decade, especially in the past 3 years, acute stroke decision-making has become complex and increasingly
individualized
First thrombolytic agent and time window defined across a population
 Alteplase, 4.5 hours
Then endovascular device and time window defined across a population
 Stent-retrievers/suction catheters, 6 hours
Finally, imaging selection criteria defined who would benefit for extended time windows out to 24 hours from
stroke onset
 CTAngio-CTPerfusion mismatch for endovascular therapy
 MRI FLAIR-DWI mismatch for thrombolysis
 Expanding the therapeutic window for acute ischemic stroke: wake-up or unwitnessed stroke onset
• 10% of stroke patients arrive within 4.5 hours of symptom onset and can be treated with IV tpa
• Up to 1/3 of stroke patients wake-up with stroke symptoms or have unwitnessed onset
• As, On history , they are disqualified from acute treatments.

28. POSITIVE DWI, NEGATIVE FLAIR MAY IDENTIFY STROKES < 4.5 HOURS OLD
90 min 125 min 130 min 282 min
DWI
FLAIR

30.  INTRACRANIAL ICA, M1 SEGMENT OF MCA, BASILAR ARTERY
 LARGE VESSEL OCCLUSION (LVO) ACCOUNT FOR ABOUT 1/3 OF ANTERIOR
CIRCULATION STROKES
 RESISTANT TO IV TPA (RECANALISATION RATES - <25%)
 WORSE OUTCOMES
 SO WE GO FOR ENDOVASCULAR INTERVENTIONS IN THESE CASES
ACUTE LARGE VESSEL OCCLUSIONS

31. ENDOVASCULAR INTERVENTIONS
• It includes
1) Intra-arterial fibrinolysis,
2) Combination intravenous and intra-arterial fibrinolysis
3) Mechanical thrombectomy/ clot disruption/clot extraction
Mechanical clot retrieval with the mechanical embolus removal in cerebral ischemia (MERCI)
retrieval system
Mechanical clot aspiration with the PENUMBRA SYSTEM
4) Acute angioplasty and stenting.

34. RECOMMENDATIONS
1) PATIENTS ELIGIBLE FOR INTRAVENOUS R-TPA SHOULD RECEIVE INTRAVENOUS R-TPA EVEN
IF ENDOVASCULAR TREATMENTS ARE BEING CONSIDERED (CLASS I; LEVEL OF EVIDENCE A).
2) PATIENTS SHOULD RECEIVE ENDOVASCULAR THERAPY WITH A STENT RETRIEVER IF THEY
MEET ALL THE FOLLOWING CRITERIA (CLASS I; LEVEL OF EVIDENCE A).
 A. PRESTROKE MRS SCORE 0 TO 1,
 B. ACUTE ISCHEMIC STROKE RECEIVING INTRAVENOUS R-TPA WITHIN 4.5 HOURS OF ONSET
 C. CAUSATIVE OCCLUSION OF THE ICA OR PROXIMAL MCA (M1),
 D. AGE ≥18 YEARS,
 E. NIHSS SCORE OF ≥6,
 F. ASPECTS OF ≥6, AND
 G. TREATMENT CAN BE INITIATED (GROIN PUNCTURE) WITHIN 6 HOURS OF SYMPTOM ONSET
3) AS WITH INTRAVENOUS R-TPA, REDUCED TIME FROM SYMPTOM ONSET TO REPERFUSION
WITH ENDOVASCULAR THERAPIES IS HIGHLY ASSOCIATED WITH BETTER CLINICAL OUTCOMES.
(CLASS I; LEVEL OF EVIDENCE B-R)
4) USE OF STENT RETRIEVERS IS INDICATED IN PREFERENCE TO THE MERCI DEVICE. (CLASS I; LEVEL OF
EVIDENCE A)

35. 5) WHEN TREATMENT IS INITIATED BEYOND 6 HOURS FROM SYMPTOM ONSET, THE
EFFECTIVENESS OF ENDOVASCULAR THERAPY IS UNCERTAIN CLASS IIB; LEVEL OF EVIDENCE C
6) OBSERVING PATIENTS AFTER INTRAVENOUS R-TPA TO ASSESS FOR CLINICAL RESPONSE
BEFORE PURSUING ENDOVASCULAR THERAPY IS NOT REQUIRED TO ACHIEVE BENEFICIAL
OUTCOMES AND IS NOT RECOMMENDED. (CLASS III; LEVEL OF EVIDENCE B-R).
7) THE TECHNICAL GOAL OF THE THROMBECTOMY PROCEDURE SHOULD BE A TICI GRADE
2B/3 ANGIOGRAPHIC RESULT TO MAXIMIZE THE PROBABILITY OF A GOOD FUNCTIONAL
CLINICAL OUTCOME CLASS I; LEVEL OF EVIDENCE A
8) ENDOVASCULAR THERAPY WITH STENT RETRIEVERS IS RECOMMENDED OVER INTRA-
ARTERIAL FIBRINOLYSIS AS FIRST-LINE THERAPY (CLASS I; LEVEL OF EVIDENCE E)
9) IT MIGHT BE REASONABLE TO FAVOR CONSCIOUS SEDATION OVER GENERAL
ANESTHESIA DURING ENDOVASCULAR THERAPY FOR ACUTE ISCHEMIC STROKE. (CLASS IIB;
LEVEL OF EVIDENCE C)
RECOMMENDATIONS

36. Stent retrievers Angioplasty and
stenting
Intra-arterial fibrinolysis
Within 6 hours of symptom onset and who
have causative occlusion of the m2 or m3
portion of the mcas, anterior cerebral
arteries, vertebral arteries, basilar artery, or
posterior cerebral arteries class iib; level of evidence c
Proximal cervical
atherosclerotic stenosis
or complete occlusion
at the time of
thrombectomy may be
considered, but the
usefulness is unknown
(class iib; level of evidence C)
Is beneficial for carefully selected
patients with major ischemic
strokes of <6 hours for MCA
occlusion(class I; level of evidence B-R)
May be reasonable for some patients <18
years of age with acute ischemic stroke(class iib;
level of evidence )
Patients with contraindications to intravenous
r-tpa, endovascular therapy with stent
retrievers completed within 6 hours of stroke
onset is reasonable (class iia; level of evidence )
The use of a proximal balloon guide catheter
or a large-bore distal-access catheter in
conjunction with stent retrievers may be

37. IV RTPA WITHIN 3 HRS
CLASS I
• CT within 20 minutes ≥50%
• Door-to-needle time within 60 minutes ≥50%
• EVT, ECG, troponin should not delay IV t-PA
• Only the assessment of blood glucose must precede the
initiation of IV t-PA
• Receive IV t-PA: BP <185/110 mmHg
• IV t-PA for AIS < 3 hr
TAKE HOME MESSAGE

38. IV T-PA FOR AIS < 3 – 4.5
HR
Class I
• for pts ≤80 y/o, without both DM and stroke hx, NIHSS ≤25, not taking
any OACs, <1/3 MCA territory by CT or MRI
Class IIa
• for pts >80 y/o
Class IIb
• taking OACs and INR ≤1.7 and/or PT <15 s
• with both DM and stroke hx
TAKE HOME MESSAGE
TAKE HOME MESSAGE

39. ENDOVASCULAR THERAPY
Class I
• AIS < 6 hr
• AIS < 6-16 hr: DAWN or DEFUSE 3 criteria
Class IIa
• AIS < 6-24 hr: DAWN criteria
TAKE HOME MESSAGE
TAKE HOME MESSAGE

40. =
TIME IS BRAIN
TAKE HOME MESSAGE

41. THANK YOU

42. TRIALS -NINDS RTPA STROKE TRIAL 1996
• use of intravenous rtpa in 1996, in which 624 patients with ischemic stroke were treated
with placebo or intravenous rtpa (0.9 mg/kg IV, maximum 90 mg) within 3 hours of
symptom onset,
• In the first trial part i, the primary end point was neurological improvement at 24 hours.
• In the second trial (part ii), the pivotal efficacy trial, the primary end point was defined as
complete or nearly complete neurological recovery 3 months after stroke.
• The major risk of intravenous rtpa treatment remains s-ich. In the NINDS rtpa stroke trial,
early minimal neurological symptoms or neurological deterioration temporally associated
with any intracranial hemorrhage occurred in 6.4% of patients treated with intravenous
rtpa.

43. ECASS I AND ECASS II
ATLANTIS A AND ATLANTIS B
• similar effects in 3hr time window to those observed in the 2 NINDS rtpa
trials
ECASS III(2008)
The ECASS III trial was undertaken to prove or disprove the benefit of intravenous rtPA in the
3 to 4.5-hour window suggested by the pooled analysis of the 4 prior trials.
trial additionally excluded people >80 years old, those with a baseline NIHSS score >25, those
taking oral anticoagulants (even if their INR was <1.7), and those who had the combination of
a previous stroke and diabetes mellitus.
Results were same as previous trial results.

44. INTERNATIONAL STROKE TRIAL (IST-
3)• In june 2012, the results from the third international stroke trial (IST-3), the largest
randomized, placebo-controlled trial to date of intravenous rtpa, were published. Eligibility
criteria were similar to other intravenous rtpa trials with several exceptions, including no
upper limit to age and broader blood pressure eligibility (systolic blood pressure 90–220 mm
hg and diastolic blood pressure 40–130 mm hg).
• Within 7 days, fatal or nonfatal S-ich occurred in 7% versus 1% in the treatment versus
placebo arms, respectively. More deaths occurred within 7 days in the intravenous rtpa group
(11%) than in the control group.SANDERCOCK AND COLLEAGUE’S META-
ANALYSIS
• meta-analysis of 12 intravenous rtpa trials that had enrolled 7012 patients up to 6 hours from
symptom onset.
• The data reinforced the importance of timely treatment, because the benefit of intravenous
rtpa was greatest in patients treated within 3 hours from symptom onset.

45. CONCLUSION
• Superior reperfusion at initial angiogram
NNT (number needed to treat) 9 to avoid thrombectomy.(9:1)
• Faster infusion / less expensive
• However, giving TNK instead of alteplase to only thrombectomy candidates affects alteplase delivery
to non-thrombectomy candidates as CT angio must be performed prior to giving the thrombolytic to
decide who will go on to thrombectomy and benefit from TNK
 Tenecteplase (tnk) is a genetically modified form of alteplase with increased fibrin specificity
and increased resistance to plasminogen activator inhibitor (pai-1) thereby leading to a longer
half-life.
 Tnk is given as a single bolus rather than a one hour infusion.
 Cheaper than alteplase
EXTEND-IA TENECTEPLASE TRIAL
EXTENDING THE TIME FOR THROMBOLYSIS IN EMERGENCY NEUROLOGICAL DEFICITS- INTRAARTERIAL

46.  Acute stroke with “last known normal” time > 4.5 hrs (no upper time limit)
 Had DWI-FLAIR mismatch (abnormal signal on DWI and no marked signal change on
FLAIR in the region of the acute stroke).
 Excluded:
Large strokes > 1/3 of MCA or NIHSS > 25
Planned thrombectomy
WAKE-UP Stroke Trial
OR DAWN TRIAL