Associate Professor of Neurology Director of Neurointerventional Services University of Louisville School of Medicine ACUTE STROKE INTERVENTION: THE ROLE OF THROMBECTOMY AND IA LYSIS
Conflict of Interest Speaker s Bureau BMS/Sanofi
Stroke is Heterogeneous Thrombi/Emboli of varying compositions
Will a Single Treatment or Modality Be Effective for All Stroke Subtypes and Stroke Patients?
Prolyse in Acute Cerebral Thromboembolism Trial: PROACT II Only randomized, placebo-controlled study of IA thrombolysis for acute ischemic stroke Homogeneous patients Ischemic Stroke <6 hours duration Angiographically proven MCA occlusion Early infarct signs on initial CT <1/3 MCA territory Furlan A. et.al. JAMA 1999;282:2003-2011
PROACT II Protocol 180 patients randomized 9mg of IA r-prouk infused over 2 hours vs. nothing Clot disruption not allowed. Heparin 2,000U bolus IV then 500U/hr IV x4hrs.
PROACT II Outcomes TIMI 2 or 3 67% Symptomatic ICH 10% Natural History NIHSS 4-10 58% Relative 15% Absolute NIHSS 11-20 NIHSS 21-30 0 10 20 30 40 50 60 70 80 90 100 mrankin 0-2 3-6
IMS Study Facilitated IA Lysis Phase II pilot study of 80 pts for acute ischemic stroke Combined IV / IA t-pa (NIHSS > 10) IV (0.6 mg/kg, 15% bolus, 30 min inf., 60 mg max.) IA (2 mg-distal, 2 mg-intra-clot, 9 mg/hr x 2 hrs, 22 mg max.) IV t-pa started within 3 hours of symptom onset Stroke 2004;35:904-912
IMS Results TIMI 2 or 3 ~ 57% Symptomatic ICH 6.3% Outcome at 3Months (%)* IMS Study (n = 80) NINDS Placebo (n = 211) Rankin 0-1 30% 18% Rankin 0-2 43% 28% NIHSS 1 25% 15% Odds Ratio (95% CI) 2.29 (1.2, 4.4) 2.04 (1.2, 3.6) 2.24 (1.1, 4.5) *Adjusted for baseline NIHSS and time-to-treatment
IA Thrombolysis Limitations Moderate Recanalization Efficacy PROACT II TIMI 3 19% TIMI 2 or 3 67% Up to 2hr for recanalization Only proven agent not available r-pro-uk- same dose for every patient tpa Neurotoxic Activates MMP-9 Breaks down BBB Increases risk of ICH Khathriet al Stroke: ICH related to use of thrombolytics 10%-38% ICH
Combined Pharmacological Approach IV tpa + Tirofiban- 19pts (NIHSS 17) TIMI 2 or 3 68% IA tpa + Eptifibatide- 49pts (NIHSS 19) IA tpa- mean 11 mg for all Pts 24 Pts- Eptifibatide 90 mcg/kg bolus 0.5-2.0 µg/kg/min TIMI 2 or 3 31% vs. 58% (p=ns) Stroke 2004;35:705, Stroke 2002; 33:359
Aggressive Mechanical Clot Disruption + Low-dose IA Reteplase After 4U of IA reteplase Angioplasty for proximal occlusion or Snare manipulation for distal occlusion 19 patients @ 1 to 9 hours Reteplase alone in 5 Angioplasty in 11 Snare in 5 Complete restoration of flow in 12 (63%) and no symptomatic ICH Neurosurgery 2002; 51:1319-27
Multimodal Treatment Treatment Tailored for Each Patient
Multimodal Therapy Abou-Chebl et al Stroke 2005 12 Patients 4 Post-operative Age 65.7±12.1 NIHSS 18.7±3.5 Range 15-25 SxDuration 3.6±2.2 Range 0.5-8hrs Occlusion 5 MCA 6 Carotid Terminus 1 BA Etiology 7 embolic 5 Atherothrombotic Lysis Lysis Result 2nd Intervention Result 3rd Intervention Result 4th Intervention Result 5th Intervention Result Yes TIMI 1 Angioplasty TIMI 2 (Reoccl) Reopro TIMI 3 None IV full dose TIMI 0 Angioplasty TIMI 0 Snare TIMI 0 Reopro TIMI 2 ICA PTA TIMI 3 No Angioplasty TIMI 2 Reopro TIMI 3 None Yes TIMI 1 Angioplasty TIMI 1 Reopro TIMI 3 Hypothermia Good None Yes TIMI 2 (Reoccl) Reopro TIMI 2 Angioplasty TIMI 2 None Yes TIMI 0 Angioplasty TIMI 2 Integrelin TIMI 2 None Yes TIMI 0 Reopro TIMI 0 Angioplasty TIMI 1 Angiojet (ICA) TIMI 2 None Yes TIMI 0 Reopro TIMI 0 Angioplasty TIMI 3 None Yes TIMI 0 Mechanical Disruption TIMI 1 Reopro TIMI 3 None Yes TIMI 0 Reopro TIMI 0 Angioplasty TIMI 0 Snare TIMI 1 (ACA TIMI 3) None Yes TIMI 0 Angioplasty TIMI 1 Reopro TIMI 3 None Yes TIMI 0 Angioplasty TIMI 0 Reopro TIMI 0 Snare TIMI 3 None
Clinical Outcome TIMI 2 or 3 92% >4 Point NIHSS Improvement 10/12 (83%) Mean Improvement 11±6.8 Mean NIHSS @ D/C 7.7±8 No or Minimal Disability (Rankin 2) 6/12 (50%) Mortality 2/12 (17%) ICH Symptomatic 1/12 (8.3%) Asymptomatic 1/12 (8.3%)
Illustrative Case 1: Multimodal Treatment 59 y.o. Male w HTN, Chol, Cigs undergoing L Heart Cath Immediately upon withdrawal of Pigtail Catheter from LV developed Neurological Sx Global Aphasia R Hemianopsia Flaccid R Hemiparesis NIHSS=22
Angiogram Acute Cutoff of L MCA Trunk Few Pial Collaterals from ACA to MCA
Endovascular Approach Retevase 3U followed by Reopro 10mg (1/2 Bolus) Injected into MCA 10 min Later Nearly Complete Flow Except for One Distal Branch Occlusion
Outcome Speech and R Arm Movement Began To Return on the Table Final Angiogram at 75 min After Onset is Normal
Mechanical Embolectomy
Mechanical Embolectomy With Commercially Available Microvena Snare Personal Experience 9 Patients All failed thrombolysis or contraindicated 4/9 Complete clot removed in first pass 3/9 Multiple passes for complete removal 2/9 Partial clot removal No complications 4/9 Rapid Complete Recovery
EKOS MicroLysUS Ultrasound Infusion Catheter 2.1-MHz Ultrasound Transducer Leary MC, et al. Ann Emerg Med. 2003 Jun;41(6):838-46
EKOS MicroLys US Infusion Catheter for Embolic Stroke 10 anterior circulation strokes treated @ 3-6 hours pre-nihss mean 18 4 posterior circulation strokes treated @ 4-13 hours 3 deaths @ 24 hours (2 ICH, 1 edema) TIMI 2-3 for 8 in first hour Mean time to recanalization 46 minutes 4 posterior circulation strokes treated @ 4-13 hours AJNR 2003; 24:534-8
Concentric MERCI Retriever System X-Series L-Series K-Mini V-Series APM0182/E/3127, 2008-02
Merci Study Device deployed in 141/151 patients Mean NIHSS 20.1 (SD ± 6.6) Recanalization Device only: 68 pts (48%) + adjuvant: 85 (60%) pts. Symptomatic ICH 7/90 pts (8%) with device only 11/141 (8%) + adjuvant tx. MRS < 2 at 90 days was 28% (36 of 130) Alex Abou-Chebl, Stroke MD2005;36(7):1432-1438
Multi Merci Trial- Result 164 patients. Age 68 + 16 Baseline NIHSS 19.3 + 6.4 From onset- groin puncture (hrs) 4.2 (3.2-5.3) Procedure duration (hours) 1.6 (1.2-2.3) Number of attempts 2.9 + 1.6 Prior IV-tPA 29% (48) Smith W. et al Stroke 2008
Multi Merci Trial L5 Retriever Retriever revascularization 54.9% (90) Retriever + Lytics 68.3%(112) Clinically significant complications 5.5% (9) Symptomatic ICH 9.8% (16) mrs 2 36% Mortality Day 90 34%
Multi MERCI-L5 subset Final Revascularization by Vessel 100% 90% 80% 69.5% 71% 66% 100% 70% 60% 50% 40% 30% 20% 10% 0% Overall Carotid MCA Vert/Bas (91/131) (29/41) (54/82) (8/8) ISC 2007, San Francisco
Multi Merci Trial- Results 50 49.1 60 51.9 40 50 30 40 20 10 9.6 30 20 10 24.8 0 MRS 0-3 Recanalized Non Recanalized 0 Mortality 90d Recanalized Non Recanalized Smith W. et al Stroke 2008
Multi MERCI Failed IV tpa Patients 48 patients with failed IV tpa in Multi MERCI trial Persistent occlusion confirmed angiographically Dose range 0.6-0.9 mg/kg Results Recanalization 73% Symptomatic ICH 10.4% Symptomatic PH-2 2.1% mrs 2 at 90 days 38.3%
Penumbra System
Penumbra Pivotal Trial N=125 Stroke within 8hrs 81.6% TIMI 2 or 3 3.2% SAE 11.2% Symptomatic ICH 57.8% >4point NIHSS improvement 32.8% Mortality FDA Approved Feb 2008
Penumbra POST-A Multi-Center, Real World Look At Penumbra System Results International Stroke Conference, San Diego, CA, 2/20/2009 Number of Patients Enrolled 139 Age in years (mean ± SD) 64 ± 15 Female 48% NIHSS (mean ± SD) 16 ± 6 Target Vessel: ICA 25% Median Time From Symptom Onset To Arterial Puncture Median Revascularization Time 4.5 hours 48 minutes MCA 51% Vertebrobasilar 24% TIMI 0 - I 96%
POST Results PS alone (n=32) PS + IA tpa (n=80) PS + IV tpa (n=50) Revascularization 78% 89% 80% Symptomatic ICH 3% 9% 8% 7.2% 90 Day Mortality 25% 20% 23% 22% 90 Day mrs 2 36% 49% 32% 40%
Illustrative Case 2 29 yo WF with no PMHx Found in AM with confusion and weakness In ED Mute, following some commands 1 hr later Plegic on R
Cerebral Angiogram
Embolectomy
Final Angiogram
Clinical Course Stabilized 1 Week later D/C to Rehab Following Commands Moves R leg Ale x Abo u- Che bl, MD
Illustrative Case 3 Progressive VB Stroke 35 yo WM Bartender Cigs, Family Hx Progressive decline over 48hours at OSH Presents with profound dysarthria, pooling of oral secretions, no horizontal gaze, ataxia, L>R hemiparesis NIHSS=18
Cerebral Angiogram LVA RVA
Post-Penumbra & Stenting
Outcome Rapid improvement Discharged to home post-op Day 3 At 6 months F/U Neurologically normal New job Vegetarian No cigs Angiogram- stents widely patent