European Course in Interventional Neuroradiology, 1st ... vs... · 13 Overall change of occlusion site (COS)10.7% in 720 endovascular candidates, subdividing into: •2.7% COS with

Pasquale Mordasini MD, MScHead of the Neurointerventional Unit

University Institute of Diagnostic and Interventional NeuroradiologyUniversity Hospital Inselspital BernDirector and Chair: Prof. J. Gralla

Are IV lytics for LVO patients presentingdirectly at thrombectomy centers

necessary?European Course in Interventional Neuroradiology, 1st Cycle Module 1 on

Ischemic Stroke, Barcelona, April 29, 2019

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Is IVTbeneficial prior to

mechanical thrombectomy?

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Arguments pro bridging

1. rtPA can be started earlier («ship-and-drip»)

2. rtPA may facilitate recanalization (enzymatic digestion)

3. rtPA may improve reperfusion of small vessels(lysis of smaller distal thrombus fragments, microvascular thrombosis)

4. Mechanical thrombectomy may be delayed or not feasible

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Arguments against bridging

1. rtPA poor recanalization rates in large vessel occlusion2. rtPA narrow time window with decreasing efficacy3. rtPA absolute/relative contraindications 4. rtPA (relative) contraindication for IA

lytics/antiplatelets/heparin5. rtPA increases risk of hemorrhage6. rtPA may produce thrombus dislocation7. rtPA impact on health care costs8. rtPA may cause life-threatening complications9. rtPA may delay EVT in some patients

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Two cohorts of patients

Stroke Center

Stroke UnitIVT

MT

„Drip & Ship“

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Stroke Center

Stroke UnitIVT

IVT MT

„Drip & Ship“ „Mothership“

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Stroke Center

Stroke UnitIVT

IVT MT

„Drip & Ship“ „Mothership“

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Bridging‘Believers’

Bridging‘Non-Believers’

Literature

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1) Preinterventional Reperfusion

2) Reperfusion Success

3) Symptomatic Intracerebral Hemorrhage

Major arguments

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Major arguments

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1. Preinterventional ReperfusionPrevalence

Tsivgoulis et al. Stroke 2017

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Pre-treatment with rtPA in LVO stroke eligible for mTE results in successful reperfusion in 1 of 10 cases.

Prevalence of reperfusion prior to EVT

Dripp-p-andd-d-Ship

MothershipM1M

M2MM

ICA Thrombus s length

Time e tooo angio

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1. Preinterventional ReperfusionTime dependency

Mueller et al. EJON 2017

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Overall change of occlusion site (COS) 10.7% in 720 endovascular candidates, subdividing into:

• 2.7% COS with TICI 0/1

• TICI 2a )

• 1.8% COS with perfusion worsening

1. Preinterventional ReperfusionWhat about mothership only?

Kaesmacher et al. Stroke 2018 14

Factors related to change of occlusion site (COS) with TICI 2a in 720 endovascular candidates

• thrombus length (1mm aOR 0.926, 95%-CI 0.87-0.99)

• cardioembolic thrombus (aOR 2.3, 95%-CI 1.1-4.6)

• IV-tPA (aOR 11.98, 95%-CI 4.5-31.6)

1. Preinterventional ReperfusionWhat about mothership only?

Kaesmacher et al. Stroke 2018

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1. Preinterventional ReperfusionAlways beneficial?

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Factors related to change of occlusion site (COS) with perfusion worsening

• Higher admission NIHSS (aOR 1.10 95%-CI 1.01-1.21)

• Carotid-T occlusion (aOR 18.62 95%-CI 3.77-92.00)

• IV tPA (4.33, 95%-CI 1.12-16.80)

1. Preinterventional ReperfusionAlways beneficial?

Kaesmacher et al. Stroke 2018

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Major arguments

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• Meta-analysis including 20 studies with 5279 patients

Kaesmacher et al. JNIS 2018

IVT + MT vs dMTdMT in IVT eligible pts

dMT in IVT ineligible pts

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2. Reperfusion SuccessTICI 2b/3

- 19/20 studies- 4220 patients

IVT-eligibledMTE patientsIVT-ineligibledMTE patients


• Overall, non-significant different rates of successful reperfusion

• Non-significant trend for higher rates of successful reperfusion in IVT eligible pts.

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no effect

2. Reperfusion SuccessTICI 3


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Major arguments

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3. Symptomatic ICHFactors related to sICH in EVT

• Cardioembolic Stroke

• Poor collaterals

• Delayed treatment

• High ASPECTS

• Diabetes

• High NIHSS

Jiang et al. PLOS ONE 2015; Hao et al. JNIS 2018; Kaesmacher et al Cerebrovasc Dis 2017

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3. Symptomatic ICH

Kaesmacher et al. JINS 2018

• Overall, non-significant trend for higher rates of sICH in IVT + MTE

• No treatment group effect

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Preinterventional Reperfusion

ReperfusionSuccess

SymptomaticICH

Outcome?

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OutcomeTreatment effect size of MT

Goyal et al. Lancet 2016 26

OutcomeFunctional independence




• Overall, non-significant trendfor lower rates of functionaloutcome in dMT

• dMT IVT-E: no difference in rates of functional outcome

• dMT IVT-IN: non-significanttrend for lower rates offuncitonal outcome

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OutcomeSame same, but different

• CAVE: Selection!

Atrial fibrillation Previous CVI


Prevalence of risk factors in dMT studies compared to bridging studies

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Individualized decision against t-PA?

• Mothership (Angio team ready) dependency of IVT efficacy !

• Carotid-T, large thrombilow efficacy + risk of perfusion worsening

• Microbleeds, striatal infarction, diabetic, high ASPECTSsICH

• Tandem sICH, antiplatelet medication

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Summary of evidence• Best evidence for bridging benefit:

pre-interventional reperfusion

• No evidence for facilitation of mechanical reperfusion

• Available literature on outcome comparison is severlybiased, the quality of evidence regarding the relative merits of IVT + MT versus dMTE is low

• Considering proximal large vessel occlusions:substantial indications for non-inferiorityweak indications for superiorityclinical equipoise»

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Is this relevant?

• Maybe we can achieve equal recanalizationresults!

• Maybe we can decrease rates of hemorrhages!

• Maybe we can avoid thrombus migration!

• Maybe we have similar (or even better?) outcome!

• Maybe we can reduce costs by skipping rtPA!

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Cohorts Mothership MothershipOcclusion Site ICA, M1 +/- Tandem ICA, M1, proximal M2NIHSSAgeSample Size 404 540Design Non-inferiority SuperiorityStart 10/2017 01/2018Countries Switzerland, France, Germany,

Spain, Canada, FinlandNetherlands

Ongoing Randomized controlled Trials

- Direct MT (China), Direct safe (Australia), SKIP study (Japan)

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Conclusion

• IVT will remain the standard of care for all patients with peripheral intracranial vessel occlusion

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Conclusion

• IVT will remain the standard of care for all patients with peripheral intracranial vessel occlusion

• But a trial is needed comparing direct mechanical thrombectomy versus bridging thrombolysis in patients with:

–proximal vessel occlusion in the anterior circulation–which can immediately be treated by endovascular therapy

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Thank you!• www.strokecenter.ch• http://www.neurologie.insel.ch/de/unser-angebot/stroke-center/stroke-richtlinien/

Documents

European Course in Interventional Neuroradiology, 1st ... vs... · 13 Overall change of occlusion site (COS)10.7% in 720 endovascular candidates, subdividing into: •2.7% COS with