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Clinical Selection for IV tPAand Endovascular Treatment

Felipe De Los Rios, MD

Medical Director, Baptist Hospital Comprehensive Stroke Center &

Baptist Health South Florida Stroke Program

Associate Professor of NeurologyUniversity of Cincinnati Department of Neurology

Disclosures

• None.

Learning Objectives

• Understand the current treatments for acute ischemic stroke

• Identify the eligibility criteria for acute stroke reperfusion therapies

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https://www.google.com/search?q=stroke+penumbra&safe=active&tbm=isch&source=lnms&sa=X&ved=0ahUKEwjtu8iisZvWAhVRgSYKhttps://www.google.com/search?q=stroke+penumbra&safe=active&tbm=isch&source=lnms&sa=X&ved=0ahUKEwjtu8iisZvWAhVRgSYKHQryAtEQ_AUICigB&biw=1422&bih=736&dpr=1.35#imgdii=6INT_R70jQspgM:&imgrc=CpgOotzLVuaPFM:&spf=1505072860734HQryAtEQ_AUICigB&biw=1422&bih=736&dpr=1.35#imgdii=6INT_R70jQspgM:&imgrc=CpgOotzLVuaPFM:&spf=1505072860734

https://www.google.com/search?q=stroke+penumbra&safe=active&tbm=isch&source=lnms&sa=X&ved=0ahUKEwjtu8iisZvWAhVRgSYKHQryAtEQ_AUICigB&biw=1422&bih=736&dpr=1.35#imgrc=CpgOotzLVuaPFM:&spf=1505072860734

https://www.google.com/search?safe=active&biw=1422&bih=736&tbm=isch&sa=1&q=underwater&oq=underwater&gs_l=psy-ab.3..0l4.1204387.1205974.0.1206186.10.10.0.0.0.0.184.1285.0j10.10.0....0...1.1.64.psy-ab..0.10.1281...0i67k1.tyeZwsEVkUA#imgrc=20c11-DsQt5NoM:&spf=1505072430633

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Acute Reperfusion Therapies

IV tPA [1995]

Endovascular Thrombectomy [2015]

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IV tpa – who is eligible?

Diagnosis of ischemic

stroke causing

measurable neurological

deficit

Last seen normal <4.5 hrs before treatment

begins

Age ≥18 years old

tPA between 3 and 4.5 hours of last seen normal is not FDA approved

Hacke. Lancet. 2004.

Benefit over Time

Exclusions and Precautions

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Tpa only with glucose and head CT scan

No use of anticoagulants

No active cancer

No renal or liver disease

No alcohol or drug abuse

No suspicion for coagulopathy or thrombocytopenia

tPA > 4.5 Hrs from LSN

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WAKE-UP (MRI)

• Selection: – Stroke on diffusion without FLAIR changes

• Stopped prematurely (funding) 503/800 pts

• Favorable outcome: mRS 0-1 at 90 days

• Results:– FO@90 days: 53.3% vs. 41.8% placebo (P=0.02)

– Deaths: 4.1% vs. 1.2% placebo (P=0.07)

– sICH: 2% vs. 0.4% placebo (P=0.15)

WAKE-UP (MRI)

• Reason for unknown last seen normal:– Wake up: 94.1% vs. 93.6% placebo

• Median interval between LSN and symptom recognition (IQR) - hr– 7.2 (4.7-8.7) vs. 7 (5-9)

• Median NIHSS (IQR)– 6 (4-9) vs. 6 (4-9)

EXTEND (CTP)

• Selection:– LSN: within 4.5-9 hrs or wake up

– mRS<2

– NIHSS 4-26

– Hypoperfused but salvageable regions• Ratio 1.2 (core to penumbra)

• Absolute difference 10 ml

• Core <70 ml

• Stopped prematurely (lack of equipoise) 225/310 pts

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EXTEND (CTP)

• Favorable outcome: mRS 0-1 at 90 days• Results:

– FO@90 days: 35.4% vs. 29.5% placebo (P=0.04)

– sICH: 6.2% vs. 0.9% placebo (P=0.05)– Death: 11.5% vs. 8.9% placebo (P=0.67)– Wake up: 64.6% vs. 65.2% placebo– Median NIHSS (IQR): 12 (8-17) vs. 10 (6-

16.5)– Core-ml: 4.6 vs. 2.4 placebo– Perfusion lesion-ml 74.3 vs. 78 placebo

Tenecteplase

•TNK 0.25 mg/kg, max dose of 25 mg•Eligible for tPA, <4.5 hours from last seen normal

Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST2)

•TNK 0.25 mg/kg vs. tPA 0.9 mg/kg•<4.5 hours from last seen normal with significant penumbra

Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) Trial

•TNK 0.25 mg/kg, max dose of 25 mg•<4.5 hours from awakening, NIHSS >5, with compatible perfusion imaging

Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

•TNK 0.25 mg/kg vs. best medical treatment (usually asa)•TIA or NIHSS ≤ 5 within 12 hours with acute intracranial occlusion or near occlusion

A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic

Stroke With Proven Occlusion (TEMPO-2)

•IV TNK 0.25 mg/kg (max 25 mg) vs. 0.4 mg/kg (max 40 mg)Determining the Optimal Dose of

Tenecteplase Before Endovascular Therapy for Ischaemic Stroke (EXTEND-IA TNK Part 2)

Endovascular Treatment

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Positive trials

MR CLEAN (2015)

ESCAPE (2015)

SWIFT PRIME (2015)

EXTEND –IA (2015)

REVASCAT (2015)

https://www.google.com/search?q=stroke+penumbra&safe=active&tbm=isch&source=lnms&sa=X&ved=0ahUKEwjtu8iisZvWAhVRgSYKHQryAtEQ_AUICigB&biw=1422&bih=736&dpr=1.35#imgdii=6INT_R70jQspgM:&imgrc=CpgOotzLVuaPFM:&spf=1505072860734

Impact

Ivie Tokunboh, et al. Stroke 2018

EVT – Who is eligible?

Prestroke mRS score 0 to 1

Treatment can be initiated (groin puncture) within 6 hours of symptom onset

Causative occlusion of the ICA or proximal MCA (M1)

Age ≥18 years

NIHSS score of ≥6

ASPECTS of ≥6

Powers WJ. 2018 AHA / ASA 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke Stroke, 2018.

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Also consider …

Although the benefits are uncertain, EVT may be reasonable for carefully selected patients with (groin

puncture) within 6 hours of symptom onset and:

• causative occlusion of the MCA segment 2 (M2) or MCA segment 3 (M3)

• Anterior cerebral artery• Vertebral artery• Basilar artery• Posterior cerebral artery• Pre stroke mRS >1• Aspects <6• NIHSS <6

Powers WJ. 2018 AHA / ASA 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke Stroke, 2018.

Combination Therapy

If last seen normal is <4.5 hours and a candidate for both tPA and endovascular treatment, both should be given without delay.

Powers WJ. 2018 AHA / ASA 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke Stroke, 2018.

Modified Rankin Scale (mRS)

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Commonly used scale to measure degree of disability or dependence in daily activities of people

who suffered a stroke

Score 0-2 considered a “good” functional outcome

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CT-Aspects score

www.aspectsinstroke.com

EVT – 24 Hrs from LSN

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Eligibility criteria

• Occlusion of the ICA, M1 (or both)

• Mismatch between the severity of the clinical deficit

and the infarct volume

• Group A (≥ 80 yo) NIHSS ≥ 10, infarct volume <21 ml

• Group B (<80 yo) NIHSS ≥ 10 infarct volume < 31 ml

• Group C (<80 yo) NIHSS ≥ 20 infarct volume 31 - 51

ml

• Age >18 yo

• Last known well 6-24 hours

• Prestroke mRS 0, 1

• Baseline NIHSS ≥10

• No infarct >1/3 of middle cerebral artery

• Life expectancy ≥ 6 months

• Occlusion of ICA, M1

• Infarct volume <70 ml

• Ratio of volume of ischemic tissue to initial infarct

volume of ≥1.8

• Absolute volume of potentially reversible ischemia ≥15 ml

• Age 18-90 yo

• Last known well 6-16 hours

• Prestroke mRS 0, 1, 2

• Baseline NIHSS ≥6

• ASPECTS ≥6

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DAWN DEFUSE III

BHM – Eligibility (24 Hrs)

Key learning points

• tPA: Potential candidates are all those who have persistent stroke symptoms and are within 4.5 of LSN (9 hrs / wake up off-label)

• EVT: Potential candidates if there are disabling deficits with NIHSS ~> 6 and within 24 hrs of LSN

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References

• Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2018;49:e46-e110

• Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. The New England journal of medicine. 2018;378:11-21

• Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. The New England journal of medicine. 2018;378:708-718

• Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, et al. Mri-guided thrombolysis for stroke with unknown time of onset. The New England journal of medicine. 2018;379:611-622

• Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. The New England journal of medicine. 2019;380:1795-1803