Ischemic Stroke 2010 and the Future Lawrence R. Wechsler, M.D. Professor and Chair, Department of Neurology, University of Pittsburgh Director, UPMC Stroke Institute

Disclosures Consultant: Abbott Vascular, NMT, Ferrer Steering committee: ACT I, CLOSURE DSMB: DIAS 3 / 4, SAPPHIRE WW Scientific Advisory Board and Stockholder: Neurointerventional Therapeutics

Outline Medical therapy for stroke prevention Recanalization Imaging in patient selection Telestroke

Stroke Prevention 2010 Risk factor control BP, diabetes, lipids Antiplatelet agents ASA, Plavix, Aggrenox Anticoagulation Afib, hypercoagulable states Carotid revascularization CEA v. CAS

Medical Therapy for Carotid Disease Study Year Surgery (% Stroke /Yr) Medical Rx (% Stroke/Yr) Difference (% Stroke/Yr) NASCET > 70% 1991 4.5% 13% 8.5% NASCET 50-69% 1998 3.1% 4.4% 1.3% ACAS 1995 1.0% 2.2% 1.2% ACST 2004 2.4% 1.1%

Optimal Medical Management 2010 Blood pressure control < 130 systolic, 85 diastolic Diuretics, ACE Inhibitors Lipids < 70 LDL, > 50 HDL HbA1c < 7% Smoking cessation Lifestyle modification – weight loss, exercise, diet

Intensive Medical Therapy for Asymptomatic Stenosis Kaplan Meier survival free of stroke, death , MI for 468 pts with > 60% asymptomatic stenosis before and after instituting intensive medical therapy p<0.001 Spence et al. Arch Neurol 2010

IV tPA for Acute Stroke Only FDA approved therapy for treatment of acute stroke 3-4.5 hr window for treatment Earlier treatment increases chance of good outcome Limitations – exclusions, large artery disease, reocclusion

PROACT II: 90-Day Outcomes Intra-arterial Prourokinase – MCA Occl (90 days) r–proUK (n = 121) Control (n = 59) Absolute ∆ P ————————— % ————————— mRS ≤ 2 40 25 15 0.043 mRS ≤ 1 26 17 9 0.16 Barthel index ≥ 90 41 32 0.24 Barthel index ≥ 60 54 47 7 0.39 NIHSS ≤ 1 18 12 6 0.30 NIHSS > 50% ↓ 50 44 0.46 Mortality 27 -2 0.80 Furlan A, et al. JAMA. 1999;282:2003-11.

PROACT II: MCA Recanalization Angiogram P < 0.001 P = 0.003 Furlan A, et al. JAMA. 1999;282:2003-11.

Mechanical Thrombectomy Concentric Medical Penumbra Not yet FDA approved: Ekos, Omnisonics, Lazarus Effect, MindFrame, Phenox

MERCI – Recanalization v. Outcome Smith WS, et al. Stroke. 2005;36:1432-40.

Recanalization v. Infarct Size RELATIONSHIP BETWEEN RECANALIZATION AND FINAL INFARCT VOLUME IN 159 PATIENTS TREATED WITH IA THROMBOLYSIS FOR ACUTE ISCHEMIC STROKE AT UPMC P < .0012 by ANOVA Zaidi et al. Stroke 2009

Time to Recanalization v. Outcome Khatri et al Neurology 2009

Recanalization by Treatment Modality – UPMC SI Pts (n) TIMI 2 – 3 TIMI 3 ———————— % ———————— IV/IA t–PA 66 61 25 IA lytic 117 57 Gp IIb/IIIa + lytic 31 81 42 Angioplasty 67 70 40 Intracranial stent 20 90 50 MERCI retriever 204 79 --- DAC 76 88 Penumbra 39 93 I superscripted ® Grace, remove all lines form tables except: rule above table rule below table header rule below table

Recanalization-Outcomes Mismatch 80-90% RECANALIZATION 40-50% RECANALIZATION WITH GOOD OUTCOMES 40-50% RECANALIZATION WITH POOR OUTCOME Time to Rx Depth of ischemia TIMI 2 v. 3 Stroke location No reflow

Tissue vs. Time Window: Selecting the right Patient < 3 Hrs > 3 Hrs Imaging required to assess pathophysiology = % Patients with Penumbra Early time is surrogate marker for penumbra Time From Onset (Hours) Courtesy MR Rescue Trial

DEFUSE: Mismatch associated with good outcomes following reperfusion Before tPA NIHSS 16 6 cc 4.5 hrs After tPA NIHSS 5 Improved 0 cc IV tPA 3 cc 65 cc ↓ M2 Flow

DEFUSE: IV tPA 3-6 Hrs Favorable Clinical Response* Target Mismatch with and without Early Reperfusion Mismatch + ER (n=15) Median NIHSS: 14 Mean Age: 79 67% 19% Mismatch - ER (n=16) Median NIHSS: 13 Mean Age: 68 Odds Ratio 8.7 P = 0.011 *NIHSS 0-1 / > 8 pt improvement at 30 days Albers et al. Ann Neurol 2006

PWI / DWI Mismatch - Quantitation

Stroke Treatment with IV tPA Only 2-8% of stroke patients receive IV tPA > 50% of hospitals < 100 beds Lack of available stroke specialist in community hospitals major impediment to emergent treatment Telestroke brings stroke experts to community hospitals

Telemedicine for Stroke Audebert et al. Cerebrovasc Dis 2005

Change in tPA Usage Before and After Starting Telestroke – Spoke Hospital Telestroke increases utilization of IV tPA Increases percent of patients treated with IV tPA

Future of Acute Stroke Therapy Reduce time to arterial recanalization Greater TIMI 3 recanalization Select patients most likely to benefit and less likely to be harmed Treat patients based on physiology not time Increase utilization of acute stroke therapy through telemedicine and stroke systems of care