RAIN 2018: Ischemic Stroke NIH U10 NS 086494 (PI) NorCal RCC - - PowerPoint PPT Presentation

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RAIN 2018: Ischemic Stroke

Wade S. Smith, MD, PhD

Chief, UCSF Neurovascular Division Professor, UCSF Department of Neurology

Disclosures

• NIH
• U10 NS 086494 (PI) NorCal RCC
• Consultant or stock ownership:
• DSMB: Stryker Inc.

Wade S. Smith, MD, PhD

Chief, UCSF Neurovascular Division Professor, UCSF Department of Neurology MR CLEAN REVASCAT SWIFT-Prime EXTEND IA ESCAPE N=1287 Randomized Patients

5 10 7.9 16.9 13.6 19.1 5 10 15 20 25 30 35 40 45 50

Control Intervention

Percent

Good Outcomes

1 2

2

3

Nogueira et al, NEJM 378: 11-21,2018 Nogueira et al, NEJM 378: 11-21,2018 Nogueira et al, NEJM 378: 11-21,2018

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Nogueira et al, NEJM 378: 11-21,2018

Albers, et al, Epub NEJM January 24, 2018 Albers, et al, Epub NEJM January 24, 2018

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Albers, et al, Epub NEJM January 24, 2018

Outcomes by Time

27 13 17 46 49 45 10 20 30 40 50 60 HERMES DAWN DEFUSE-3 Control Thrombectomy

IV t-PA effect? Ischemic Creep?

Late Window Paradox

Albers, Stroke: 2017 ePub

UCSF Acute Stroke Protocol

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2018 UCSF Acute Stroke Protocol

Major Conclusions

• Embolectomy with stent retrievers improve clinical
• utcome if done with 24 hours of symptom onset for

anterior circulation ischemia

• Earlier treatment improves outcome if onset < 6

hours

• Thrombectomy is safe and effective from 6-24 hours

provided they have favorable perfusion

• You should be performing CTA in all patients seen

within 24 hours of ischemic stroke onset

University of California, San Francisco

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NEUROCRITICAL CARE PROGRAM

UC SF

Intracerebral Hemorrhage: Acute and Long-Term Blood Pressure Management

• J. Claude Hemphill III, MD, MAS

Kenneth Rainin Chair in Neurocritical Care Professor of Neurology and Neurological Surgery University of California, San Francisco Chief of Neurology, San Francisco General Hospital Past-President, Neurocritical Care Society

Disclosures Research Support: NIH/NINDS; Cerebrotech Medical Stock (options): Ornim

Intracerebral Hemorrhage (ICH) - Case

• 55 yo construction exec

– Poorly controlled hypertension – Slumps over table at board meeting

• Arrives at ED 30 min after onset

– GCS 9 – BP 225/110

• What do you do with the BP?

– Now? – Later?

2015 AHA ICH Guidelines

(used IV nicardipine infusions)

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ATACH 2

• N=1000

– Worldwide – 56.2% of participants were Asian – More than half had GCS=15 – Median hematoma volume ~10 cc

• Intervention – intravenous nicardipine infusion for

24 hours to meet systolic blood pressure target

• Outcome – unable to walk or worse

– 38.7% in SBP < 140 mmHg group – 37.1% in SBP < 180 mmHg group

• Trend towards more adverse events at 3 months in

< 140 mmHg group (esp renal [posthoc])

Qureshi NEJM 2016

• Difference in Blood Pressure
• No difference in outcome

Qureshi NEJM 2016

2015 AHA ICH Guidelines New Definition of Hypertension

• American Heart Association recently dramatically

revised its definition of high blood pressure and guidelines for management.

– Whelton JACC 2017

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What About ICH?

Whelton JACC 2017

• “Update” to 2015 AHA/ASA ICH Guidelines as a result of ATACH2
• So what is the target now?
• At UCSF and ZSFG we have changed to SBP < 160 mmHg

BP in ICH – Practical Considerations

• High blood pressure is

– The most common cause of ICH – Is present in most patients with acute ICH regardless of cause of ICH – Is the most important target for primary and secondary prevention of ICH

• Acute BP treatment

– May not be as beneficial as we hoped – Has not been compared against “no treatment” – May be more complex than we hoped » Variability may be bad (Manning Lancet Neurol 2014) » One size may not fit all – Precision Medicine needed

• Example in periop care: Futier JAMA 2017

BP in ICH – Practical Considerations

What to Do?

• Acute BP Management in ICH

– Lower the BP – Select an intermediate target. » SBP < 160 mmHg for at least 3 days?

• Long-term BP Management in ICH

– Select a target. < 130/80 mmHg in most cases – Discharge patient on BP meds and write the target in the chart – Recognize high BP in the office and start treatment (time to dispense with notion of “white coat” hypertension)

2/16/2018 1

Will We Ever Truly Have Closure? PFO Following Stroke

• S. Andrew Josephson MD

Carmen Castro Franceschi and Gladyne K. Mitchell Neurohospitalist Distinguished Professor Chair, Department of Neurology Director, Neurohospitalist Program University of California, San Francisco

The speaker has no disclosures

The “Absolute Mess”

• f PFO in Stroke
• Around 20-25% of all patients have a PFO
• PFO alone is not necessarily associated with

higher risk of recurrent stroke

– Higher risk: Larger PFO, associated atrial septal aneurysm, perhaps younger age

• Three previous negative trials of closure

devices but cardiologists pre-2017 were still performing these procedures widely

Case Study

• A 76F presents to stroke clinic following an

embolic-appearing stroke

• Workup for etiology was negative except

ipsilateral 30% carotid stenosis

• She has a “very small” PFO on TTE
• I have an extensive discussion about the (lack
• f) significance of this lesion and our plans to

not intervene: She is delighted

RESPECT Gore REDUCE CLOSE Inclusion Criteria Cryptogenic stroke within past 270 days + PFO Cryptogenic stroke within past 180 days + PFO Stroke attributed to PFO + atrial septal aneurysm OR large PFO Participants 980 participants 644 participants 663 participants Intervention Arm PFO closure PFO closure + antiplatelet PFO closure + antiplatelet Medical Rx Arm Antiplatelet or anticoagulation Antiplatelet Arm 1: antiplatelet Arm 2: anticoagulation Results Less recurrent stroke with PFO closure (NNT 42) Less recurrent clinical and clinical+radiographic stroke with PFO closure (NNT 28) Less recurrent stroke with PFO closure (NNT 20)

New Data: N Engl J Med 2017

2/16/2018 2

2018 Meta-Analyses

• Many more to come; all only as good as the

primary trials they are examining

• Each included 4 of the 5 trials as one device

tested previously no longer commercially available and not particularly effective

Shah R et al and DeRosa S et al Ann Intern Med 2018 Shah R et al and DeRosa S et al Ann Intern Med 2018 Shah R et al and DeRosa S et al Ann Intern Med 2018

What now? “Let’s close all these PFOs!”

• DO NOT close all these PFOs
• DO screen patients for PFO (?how)
• It is sensible to discuss with your

cardiologists some “Rules of the Road”

• At the end of the day, this is an exciting

advance for some (young) people with stroke that can make a substantial impact on recurrence rates

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Rules of the Road

• Consider PFO closure if:

– The patient is younger than 60 years old – AND you can be sure the PFO is the most likely etiology after a thorough workup – AND the qualifying event is a stroke (not TIA) that appears embolic (not lacunar) – Likely concentrate on large PFOs or those with an atrial septal defect

• Cardiologists new task: start counting bubbles

Risks to Discuss With Your Patients

• Atrial Fibrillation rates higher
• No great data beyond 5-10 years
• Antiplatelet regimens variable but most

include duals for some time and then monotherapy

– And what if AF develops?

• Major risk for stroke is up front rather than

spread throughout subsequent years

• Medical management: Options appear equal

2/16/2018 1

UPDATE ON INTRACRANIAL ANEURYSM

Nerissa U. Ko, MD, MAS Recent Advances in Neurology February 15, 2018

Current controversies

• Screening for unruptured aneurysms
• Who to screen?
• What to do with small aneurysms?
• When to screen?
• How often?
• Predicting aneurysms at high risk for

rupture

• Any risk factors?
• When to treat?

Guideline recommendations

• Family history > 2 first

degree family members with IA or SAH

• Genetic risk factors
• Polycystic kidney disease
• Ehler’s-Danlos, aortic

coarctation, microcephalic

• steodysplastic primordial

dwarfism

• History of prior SAH
• Non-invasive imaging

initially 6-12 months (CTA/MRA/DSA)

• Follow-up one year or

every other year to determine if:

• Aneurysm size > 7mm
• Aneurysm enlargement
• Consideration for treatment

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2/16/2018 3

2/16/2018 4

• PHASES score
• Population

(Finnish, Japanese)

• HTN
• Age > 70
• Size
• Hx SAH
• Aneurysm location
• Score < 3 associated

with lower, but not negligible risk of bleed

Summary

• Small aneurysms have a very low risk of

growth and rupture

• Recent modeling and systematic review

studies recommend no monitoring or intervention in small aneurysms in the general population

• However, the dilemma of identifying which

small aneurysm will rupture remains problematic

Future directions

• Better selection of high risk patients to

monitor, including women with FMD

• Use of new grading scales like PHASES if

validated

• Biological imaging of growth, areas of

activity

• High resolution MRA, feromoxytol
• Development of biomarkers to predict risk
• DNA, mRNA, microRNAs, proteomics

Page 1

NEUROCRITICAL CARE PROGRAM

UC SF

New AHA Guidelines

• A. Treat BP to goal of < 180/105 mmHg

after IV tPA

• B. Treat BP acutely if < 220/120 mmHg if

no intervention

• C. Treat BP to goal < 180/105 mmHg after

embolectomy

• D. Treat BP acutely if > 220/120 mmHg if

patient has CHF, other co-morbidities What is the blood pressure management after acute ischemic stroke? All of the following are correct except…

T r e a t B P t

• g
• a

l

• f

< 1 8 . . . T r e a t B P a c u t e l y i f < 2 2 . . . T r e a t B P t

• g
• a

l < 1 8 / . . . T r e a t B P a c u t e l y i f > 2 2 . . .

13% 27% 11% 48%

New AHA Guidelines

• A. Echocardiogram
• B. Extended cardiac monitor
• C. Fasting lipids
• D. Intracranial vessel imaging
• E. None of the above

What is recommended in standard diagnostic workup after acute ischemic stroke?

E c h

• c

a r d i

• g

r a m E x t e n d e d c a r d i a c m

• n

i t

• r

F a s t i n g l i p i d s I n t r a c r a n i a l v e s s e l i m a g i n g N

• n

e

• f

t h e a b

• v

e

18% 13% 13% 29% 27%

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PFO Patient Case - Question

• A. Yes
• B. No

Would you close a large PFO in a 35 year old with an embolic stroke and atrial fibrillation?

Y e s N

• 46%

54%

PFO Patient Case - Question

• A. Yes
• B. No

In patients with PFO and stroke, do you routinely screen for lower extremity DVT?

Yes No

40% 60%

ICH Patient Case - Question

A. SBP < 160 mmHg

• B. MAP < 110 mmHg
• C. SBP < 140 mmHg
• D. SBP < 180 mmHg

E. MAP < 140 mmHg

SBP < 160 mmHg MAP < 110 mmHg SBP < 140 mmHg SBP < 180 mmHg MAP < 140 mmHg

68% 4% 3% 14% 11%

55 yo man with a 40 cc right basal ganglia ICH, chronic hypertension with refusal to take outpatient medications, and an admission BP of 225/130 (MAP 162). His Glasgow Coma Scale score is 7. What is your goal blood pressure after 6 hours?

ICH Patient Case - Question

A. Perform neurological exams every 2 hours to watch for worsening

• B. Place a ventriculostomy and drain CSF at a

level of 10 cmH2O above the tragus

• C. Place a ventriculostomy and measure ICP,

draining CSF to keep below 20 mmHg

• D. Place a ventriculostomy and instill 2 mg of t-

PA into the ventricles E. Call a neurosurgeon to use an endovascular scope to remove the intraventricular clot 49 yo man with a small caudate ICH and significant intraventricular hemorrhage with

• hydrocephalus. His Glasgow Coma Scale

score is 10. You decide to:

P e r f

• r

m n e u r

• l
• g

i c a l e x . . . P l a c e a v e n t r i c u l

• s

t

• m

y . . . P l a c e a v e n t r i c u l

• s

t

• m

y a . . P l a c e a v e n t r i c u l

• s

t

• m

y a . . C a l l a n e u r

• s

u r g e

• n

t

• u

. .

15% 14% 16% 16% 39%

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Highlights of New AHA Acute Ischemic Stroke Guidelines

• IV Alteplase should be administered

within 4.5 hours to eligible patients, with faster door to needle times recommended (goal 45-60 min)

• Use of telestroke and teleradiology to

faciltate acute stroke management and triage, prioritize CT and CTA.

• Expanded mechanical thrombectomy

indications within 6 hours and 6-24 hours in selected patients

Highlights of New AHA Acute Ischemic Stroke Guidelines

• Carotid imaging within 24 hours,

revascularization between 48h and 7 days in eligible patients

• Dual antiplatelet therapy with aspirin

and clopidogrel within 24 hours and continued for 21 days in mild stroke patients not treated with IV tPA

• Start oral anticoagulants in patients with

atrial fibrillation within 4-14 days

• High-intensity statin in patients with

atherosclerosis < 75 years old

Other ISC Trial Highlights

• Tenecteplase non-inferior to alteplase.

Showed improve outcomes wht embolectomy (EXTEND-IA TNK)

• Rivaroxiban (2.5 mg) + aspirin

decreased secondary stroke by half (COMPASS trial)

• First stroke reduced by 44 percent with

candesartan/HCTZ, rosuvastatin 10 mg (HOPE-3 trial)