5/31/2018. Interventional Therapies that Expand Time Windows for Acute Ischemic Stroke Treatment. Disclosures. Impact of clot burden

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1 Good Outcome (%) Rankin 0-2 at 90 days 5/31/2018 Interventional Therapies that Expand Time Windows for Acute Ischemic Stroke Treatment Disclosures Cerenovus: I am on Executive Committee for ARISE2 Trial that studied the EmboTrap Device. Stryker: Paid Consultant H O R M O Z D B O Z O R G C H A M I, M D A S S I S T A N T P R O F E S S O R O R E G O N H E A L T H & S C I E N C E S U N I V E R S I T Y P O R T L A N D V A H O S P I T A L I also am involved with or Primary Investigator for several Industry-Sponsored Trials: Janssen Medtronic Microvention Stryker Biogen Daiichi Sankyo Large vessel occlusions Impact of clot burden SCOPE OF THE PROBLEM Common: 40-50% of all ischemic stroke Severe: 5x higher mortality, 3-fold reduction in good outcome Respond poorly to intravenous thrombolytic (tpa) Successful opening of occlusion by Intravenous tpa: Middle Cerebral Artery: 25-35% Carotid Terminus: Less than 10% Successful opening of the artery associated with improved outcome 138 Patients Acute MCA occlusion All treated with IV-tPA Successful Opening ~40% success Clots < 5 mm long are very likely to open with intravenous tpa. Clots > 7 mm long NEVER opened with intravenous tpa. Persistent Occlusion LENGTH OF BLOOD CLOT (mm) Riedel et al. Stroke. 2011; (42): Modern Randomized Clinical Trials of Endovascular Therapy Number Needed to Treat Endovascular 0 MR CLEAN P<0.05 CT REVASCAT P<0.05 ASPECTS ESCAPE P<0.001 Collaterals SWIFT PRIME P<0.001 RAPID 80% EXTEND-IA P<0.01 RAPID 100% 33% 44% 53% 60% 71% Control 19% 28% 29% 36% 40% 1

2 Stroke Therapy Timeline Modern Options for Mechanical Clot Retrieval Prayer Until 1996 IV tpa 1996 IA tpa 1999 MERCI/ Penumbra 2004/ 2008 Solitaire /TREVO 2012 Trevo Device Solitaire Device Aspiration Thrombectomy Stentrievers Newest FDA Approved Device Results of ARISE2 (Non-Randomized) Cerenovus: Embotrap/Embotrap 2 Device OHSU largest US Enroller in study Note, because not randomized, cannot directly compare fairly to other devices Endovascular Treatment Modalities Guide Catheter Selection Lots of different subtle nuances that can potentially alter outcome Balloon Guide Catheter versus Non-Balloon Guide Catheter Use General Anesthesia versus Conscious Sedation Intermediate Catheter use Two main methods of Guide Catheter support used Balloon Guide Catheter: often large, a bit more difficult to introduce Standard Sheath with/without additional Intermediate Catheter: easier navigation, smaller arteriotomy AHA recommends centers have fellowship-trained in Neuro-Intervention performing these procedures 2

3 Guide Catheter Selection Guide Catheter Selection STRATIS Registry Balloon Guide with Solitaire (n = 504) Non-BGC with Intermediate Catheter (n = 301) Similar baseline characteristics Balloon Guide Non-BGC Number of passes (p = ) Time of Groin to pass 24.9 min 23.1 min (p=0.0024) % mrs % 50.2% (p=0.0020) Yet based on Stryker and Medtronic Sales Data, only 30-40% use BGC??*** **Not randomized data ***based on internal company sales figures ISC Feb 2017 Imaging Modalities Used at OHSU Non-Contrast Head CT How do we now determine if a patient should get thrombectomy? ASPECTS Score: Hypodensity on CT: 10 = normal 0=all areas hypodense +Thrombectomy trial favorable outcomes w/ ASPECTS 6-10 (maybe 5?) ASPECTS: Normal vs. ASPECTS 4 CT Perfusion: RAPID 3

4 What to do if you don t have Perfusion? CT Head with ASPECTs Score + CTA Head/Neck + NIHSS >6 Likely reasonable approach in patients with minimal white matter disease and younger patients Pitfall: Example of 84 yo with lots of white matter disease How does one accurately score that? MRI Brain + Vessel Imaging + NIHSS Essentially using a MRI DWI to Clinical Exam mismatch How things were done at OHSU before RAPID Case Example, 83 yo F 23 hrs from onset NIHSS 20 MRI Brain + Vessel Imaging + NIHSS Why so low? Essentially using a MRI DWI to Clinical Exam mismatch How things were done at OHSU before RAPID Case Example, 83 yo F 23 hrs from onset Delay in Diagnosis, most often due to patient inability to call EMS Delay in receiving the therapy due to lack of availability Denial (especially Right MCA strokes)?narrow Therapeutic Time Window? NIHSS 1 Pre 24hrs Why time isn t everything Why time isn t everything The rate of Stroke Evolution is different for different folks The rate of Stroke Evolution is different for different folks 2.5 hours from onset 6 hours from onset 4

5 Why time isn t everything Trevo Registry Data The rate of Stroke Evolution is different for different folks 30 hours from onset Case Example CTH/CTA at OSH 65 yo M, no sig PMH except for unpurposeful 20 lbs weight loss in last 2 months LKN 12:30am night prior, found at 8 am with left hemiplegia, and gaze deviation Telestroke performed, NIHSS 11 Transferred to OHSU Arrival OHSU 10:48 am. LKN 00:30am Art Stick 11:25 5

6 Good Collaterals Device Deployed 11:39 Device Deployed TICI 2B ~11 hours ~ 11hrs from LKN NIHSS 11 on presentation, NIHSS 0 by 48 hours DAWN Trial published January 4, 2018 Asymptomatic Hemorrhage Initial CTH at OHSU 6

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8 DEFUSE3 Trial Released at ISC 2018 DEFUSE 3 Study DEFUSE3 Study Hypothesis: Stroke patients with MCA and/or ICA occlusion and salvageable tissue identified by CT/MR perfusion benefit from endovascular thrombectomy between 6-16 h. Design: Eligible patients randomized to thrombectomy (FDA cleared device) vs. medical management alone Key Inclusion Criteria Age NIHSS 6 or greater Premorbid mrs 0-2 Femoral Puncture within 6-16 hours Endpoint: Modified Rankin Scale, blinded assessor, day 90 Primary: ordinal shift analysis; Secondary: mrs 0-2 DEFUSE3 DEFUSE3 Results Key Imaging Inclusions: ASPECTs score 6 or greater CTA/MRA confirmed M1 or ICA occlusion CBF Core <70 ml (purple) Infarct Ratio 1.8 or greater Reversible Penumbra (green-purple) >15 ml 8

9 DEFUSE3 Primary Safety Outcomes DAWN and DEFUSE3 Criteria DAWN DEFUSE 3 Time 6 to 24hrs 6 to 16hrs Upper Age Limit none 90 year old NIHSS 10 6 mrs Imaging Criteria < 1/3 MCA territory on CT or MRI ASPECTS 6 or Greater 80yo if core 20mL Ischemic core < 70mL < 80yo Mismatch Ratio >1.8 - NIHSS 10 to 19 with core 30mL Min Penumbra >15mL - NIHSS 20 with core 31 to 50mL AHA Guidelines Updated Upcoming Device Trial at OHSU The Tigertriever from Rapid Medical: An adjustable stentriever so that you can adjust size as needed Will likely be more user dependent Investigational Device, Not FDA approved or available commercially inusa Other Devices in the Works Conclusions From MIVI, the DAISe Device Unique material provides a vessel conforming, mechanical backstop which may aide in clot capture and reduce clot loss during retrieval. May study this in future Interventional Ischemic Stroke therapies work and can work up to 24 hours (potentially longer, just not studied) (If you select the right patients) Imaging criteria is now a fundamental factor that determine eligibility Basically want to see small areas of dead brain with large areas of brain at risk and a vessel occlusion as a cause With many complexities (and comorbidities) in this patient population, it is often best to have patients treated at centers with fellowship training in Neuro- Intervention Lots of new investments and research in this area with likely more changes to come *In development, not FDA Approved 9

10 Thank You 10