Significant Relationships

Transcription

1 Opening Large Vessels During Acute Ischemic Stroke Significant Relationships Wade S Smith, MD, PhD Director UCSF Neurovascular Service Professor of Neurology Daryl R Gress Endowed Chair of Neurocritical Care and Stroke Boehringer-Ingelheim: Research Grant Support Concentric Medical: Consultant, own Stock Natural History of Large Vessel Occlusion Mortality ICA-T: 53% - Jansen, 1995, n = 32 MCA: 27-78% BA: 56% - PROACT Control, n = 59 - Hacke, 1996, n = 55 - Smith, in press Flint et al, StrokeRounds, (2004) 10:1-6 ( 1

2 Intraarterial Thrombolysis PROACT-II: mrs 2 Patients mrs 0-2 (% ) * All Baseline NIHSS Placebo r-prouk * OR 213 ( ), p=0043 MERCI/Multi MERCI Target Vessels X6 2

3 3

4 Stroke (2005) 36:1432 MERCI Clinical Outcomes p < p = Percen Recanalized Not Recanalized Stroke (2005) 36: Good Outcome Mortality (90 day) 4

5 MERCI mrs 2 Stroke (2005) 36:1432 CLOTBUST Cohort Tsivgoulis et al, Stroke :961 5

6 Multi MERCI Trial Design Goal: Test the safety and efficacy of a newer generation thrombectomy catheter (L5) in acute large vessel stroke Single arm, international multi-center, prospective design Prior use of IV t-pa was allowed Adjuvant IA t-pa also allowed Key Inclusion / Exclusion Inclusion Acute large vessel stroke (M1- M2, intracranial carotid, basilar or vertebral) NIHSS 8 First pass of device within 8 hours of symptom onset Exclusions Significant mass effect with midline shift Proximal vessel stenosis > 50% Sustained BP > 185/110 INR > 30 Platelets < 30,000 Primary Endpoints Endpoints Achievement of successful revascularization in all treatable vessels (M1/M2 segments of MCA, ICA, vertebral, basilar) Compilation of major device-related complications defined as: vessel perforation intramural arterial dissection significant embolization in a previously uninvolved arterial territory Secondary Endpoints Patient s neurological status at 90 days using the NIHSS Score and Modified Rankin Scale Symptomatic Intracranial Hemorrhage at 24 hours 15 Centers- 164 patients January July 2006 Saint Luke s Kansas City, MO Riverside Methodist Columbus, OH Oregon Health Sciences University Portland, OR Hartford Hospital Hartford, CT UCLA Medical Center Los Angeles, CA Swedish Hospital- Denver, CO Florida Hospital Orlando, FL NY Presbyterian/Cornell New York, NY Georgetown University Washington, DC Stanford University Palo Alto, CA University of Alberta- Alberta, Canada NY Presbyterian/Columbia New York, NY University of Calgary- Alberta, Canada Baptist Memorial Memphis, TN UPMC- Pittsburgh, PA 6

7 Demographics Stroke Characteristics Number of Patients Age, mean ± SD (yr) Female Baseline NIHSS, mean ± SD Site of vascular occlusion ICA/ICA-T (n=52) Middle cerebral artery (N=98) Vertebrobasilar artery (N=14) ± % 193 ± 64 32% 60% 8% Primary Results Patients Enrolled Retriever Revascularization % (n) Post Adjuvant Revascularization % (n) Clinically Significant Procedure Complications, % (n) Non-clinically significant device complication, % (n) Symptom onset to groin puncture, hr (median [IQR]) Procedure duration, hr (median [IQR]) Attempts to remove clot (mean ± SD) IV t-pa pretreatment, % (n) % (90) 683% (112) 55% (9) 06% (1) 42 [32-53] 16 [12-23] 29 ± 16 29% (48) Multi-MERCI L5 vs X5/X6 Percen Device Recanalization 695 MERCI Multi MERCI L5 7

8 Final recanalization by vessel Secondary Results Clinical Outcomes Vessel Intracranial Carotid MCA Vertebrobasilar Overall Revascularization 65% 67% 86% (34/52) (66/98) (12/14) L5 Revascularization 71% 66% 100% (29/41) (54/82) (8/8) Assessment Favorable outcome, 90 d mrs 2 Mortality at 90 days Overall N=164 36% 34% L5 Subgroup N=131 37% 34% Overall Revascularized N=112 49% 25% Overall Non-Revasc N=52 96% 52% P Value <0001 <0001 Multi MERCI Clinical Outcomes Multi MERCI Clinical Outcomes p < 0001 p < Recanalized Not Recanalized 40 Percent Good Outcome Mortality (90 day) 8

9 Secondary Results Intracranial Hemorrhage Symptomatic ICH*, % (n) Asymptomatic ICH, % (n) Asymptomatic Isolated HI-1, % (n) 98% (16) 305% (50) 110% (18) 16 (98%) *- Decline in NIHSS of 4 or more points, and any blood on post procedure CT 4 (24%) MERCI/Multi MERCI Part 1 Cohort (N=252) 80 patients with ICA-T occlusions Recanalization in 53% with retriever Recanalization in 63% (10/14) with adjuvant therapy ICA/ICA-T Occlusions MERCI/Multi MERCI Part 1 Non-recanalized * Recanalized mrs 0-2 mrs 3 mrs 4-5 Dead mrs 0-2 Mortality Variable Recanalized Hypertension OR (95% CI) 284 (26 to >999) 015 (004 to 057) P value OR (95% CI) 016 (005 to 051) P value 0002 *P=<0001 Values in Percent NIHSS 086 (074 to 100) 005 Age group (decade) Hemorrhage 107 (103 to 113) 88 (083 to 925) Flint et al, submitted for publication 9

10 Rha & Saver, Stroke :967 CLOTBUST Cohort Tsivgoulis et al, Stroke :961 PROACT-II N=180 IMS-I N=80 IMS-II N=73 MERCI N=141 Multi MERCI N=164 Trial PROACT-II JAMA 282 (1999) IMS-I, II Stroke 35 (2004) Stroke 37 (2006) 708 MERCI Stroke 36 (2005) Multi MERCI AJNR 27 (2006) Recanalization Rx 66% 56% 58% 60% 48% 68% 55% Cont 18% Outcome (mrs 2) Rx 40% 43% 45% 28% 36% Trial Design Cont 25% Rx 25% 16% 16% 44% 34% Mortality Cont 27% Randomized, IA pro-uk vs IV heparin Registry, IV t-pa + IA t-pa Symptomatic ICH Rx 10% 63% 11% 78% 98% 24% Cont 2% Registry, IA thrombectomy, IA & IV lytics allowed Baseline NIHSS Registry, IA thrombectomy, IA lytics allowed, IV disallowed Rx Cont 17 Conclusions Large vessel stroke is highly morbid Recanalization is highly associated with good clinical outcome Lack of randomized data Supporting one strategy over another (mechanical, lytic, combination, ultrasound) Any one technique is proven to treat stroke IMS-III, MR-RESCUE ISC 2007, San Francisco 10

11 Day 0 67 year old woman, dense right hemiparesis, intact language, NIHSS = 13, received t-pa 09 mg/kg at 3 hours, air lifted to UCSF, imaged with CTA/CTP at 5 hours 11

12 UCSF Acute Stroke Protocol * Day 0 Day 2 * CT, CTA (chest through brain), CTP, post-contrast CT 12

13 Thrombectomy: Imaging Guided 74 year old man, awoke with global aphasia, no motor weakness Last seen normal at midnight, first CT scan done at 9:24 AM LSN at midnight; scan at 9:24 AM T=0 T=83 min T=0 T=83 min LSN at midnight; scan at 9:24 AM Penumbra in green, core infarct in red Diffusion images done 83 minutes after CTP 13

14 A/G at T=150 min after CTP A/G at T=200 min after CTP A/G at T=220 min after CTP A/G at T=300 min after CTP; s/p 2 passes Concentric K type device; IA t-pa 2 mg X 2 14

15 T=0 T= 83 min T=330min T=25 hrs UCSF Acute Stroke Protocol * * CT CTA (chest through brain), CTP, post-contrast CT 15