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1 Disclosure Intracranial Atherosclerosis an update None Mai N. Nguyen-Huynh, MD, MAS Assistant Professor of Neurology UCSF Neurovascular Service February 7, 2009 Case #1 60 y.o. Chinese-speaking speaking woman h/o anxiety/depression, HTN, c/o HAs. PCP obtained a MRI/MRA brain. Found several areas of significant intracranial atherosclerosis. Refer to Neuro Meds: HCTZ What to do next? a) Start antiplatelet b) Start coumadin c) Start a statin d) Get a diagnostic catheter angiogram e) Get CTA f) Refer to NIR for angioplasty/stenting Case #2 66y.o. Filipino man h/o HTN, DM, presented with left sided weakness. Found on CT/CTA to have intracranial occlusion of right M2, severe (70-80%) bilateral vertebral stenoses. Meds: lisinopril, HCTZ, glucophage, ASA What to do next? a) Add Clopidogrel to ASA b) switch to Clopidogrel alone c) Switch to Aggrenox d) Start a statin e) Refer to NIR for angioplasty/stenting of vertebral arteries 1

2 Asians in the U.S. ~4% of the U.S. population Fastest growing ethnic group in U.S. Estimated to make up ~10% of the population by 2050 Many studies on race-ethnic ethnic disparities in health focus on African Americans & Hispanics. Few stroke studies on Asians in the U.S. Stroke #3 killer in the US, #1 in China #1 long-term disability in the world Higher incidence rates in Asia compared to U.S.: 39% greater in Japan 23% greater in Taiwan 81% greater in Northern China Stroke Cerebrovascular system ~795,000 strokes per year in the US 2009 costs estimated ~ $68.9 billion ~87% ischemic 8-10% with intracranial atherosclerosis (ICAD)= 47,600 to 59,500 strokes per year Extracranial carotid dz 100, ,000 cases/yr Afib 70,000 cases/yr 2

3 Circle of Willis Webanatomy.net and meddean.luc.edu Epidemiology of ICAD Northern Manhattan Stroke Study (Sacco et al., 1994) >39 y.o. hospitalized w/ acute ischemic stroke N=483 (35% black, 46% Hispanic, 19% white) 75% got TCD, 12% catheter angio 9% had extracranial dz, 8% had ICAD ICAD higher in non-whites (OR=4.4, CI ; adjusted for age, education, IDDM, hyperlipidemia) Epidemiology of ICAD Johns Hopkins study (Wityk et al., 1996) Consecutive patients admitted with acute ischemic stroke or TIA over 2yrs N=274 (61% black, 39% white) 156 patients (57%) had evaluation of intracranial vessels by MRA, TCD or catheter angio Of all patients in study, 12% had ICAD Symptomatic ICAD = 8% of total No difference between races Race-Ethnicity & ICAD Prevalence varies by race-ethnicityethnicity ICAD responsible for ischemic stroke is estimated to be: 6-29% in Blacks 11% in Hispanics 22-26% 26% in Asians Very limited data on ICAD among Asians in the US 3

4 ICAD rates in Asia # subjects ICAD rate Technique Chinese in Boston 24 43% Angio China (asymptomatic) 590 7% TCD Hong Kong % TCD Korea % Angio Taiwan % MRA Taiwan % TCD Diagnosing ICAD Transcranial Doppler (TCD) MR Angiogram (MRA) CT Angiogram (CTA) Digital Subtraction Angiography (DSA) Gold standard Transcranial Doppler (TCD) TCD Non-invasive Cheap Readily available in the community Highly operator-dependent Not feasible on every patient Still no standardized velocities SONIA (Stroke Outcomes & Neuroimaging of Intracranial Atherosclerosis): 407 patients 50-99% stenosis. Compared to DSA: PPV=55%, NPV=83% 4

5 Magnetic Resonance Imaging (MRI) MR Angiography Minimally invasive Better vessel image More expensive Not readily available in the community Flow dependent Tends to overcall degree of stenosis in higher grade due to turbulence SONIA: PPV=66%, NPV=87% Computed Tomography (CT) CT Angiogram 5

6 CT Angiogram DSA Minimally invasive; uses iodinated contrast Better vessel visualization Relatively cheap Can be readily available in the community Potential allergy to IV contrast Compared to DSA, for >50% stenosis: sensitivity = 97.1%, specificity=99.5%* *Nguyen-Huynh, MN et al., Stroke, 2008 Basilar Carotid Siphon DSA Pathology -- ICAD Considered gold standard for its high spatial resolution Most invasive; uses iodinated contrast Most expensive Most time consuming Only available at major medical centers Requires highly specialized expertise Risk of stroke ~1% 6

7 Risk Factors for ICAD Non-modifiable: Gender (female>male) Race-ethnicity ethnicity Age (younger in Asians) Modifiable: HTN DM Smoking Hyperlipidemia Diet Physical inactivity Obesity Stroke Risk in Symptomatic ICAD Annual stroke rate in ICAD on medical therapy: 8-10% in the carotid siphon About 22% over 14 mos. in vertebral or basilar artery Overall risk of recurrent stroke in patients with symptomatic ICAD is as high as 15-17% per year (WASID study) Treatment Options for ICAD Antiplatelets Still 1 st line therapy Anticoagulants Angioplasty Intracranial stenting Bare metal stent Drug-eluting coronary stent Self-expanding expanding intracranial stent WASID Warfarin-Aspirin Symptomatic Intracranial Disease Study Randomized, double-blinded, blinded, multi-center TIA & non-disabling stroke, enrolled between Feb 1999 to July 2003 Warfarin (INR ) vs. 1300mg Aspirin Primary endpoint: ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke Chimowitz, MI et al., NEJM 2005; 352:1305 7

8 WASID Stopped after 569 enrolled Mean f/u 1.8 years Mean INR= % achieved INR Major hemorrhage 3% in ASA, 8% in warfarin (HR 0.39 in favor of ASA, 95% CI , 0.83, p<0.01) 1-yr rate of ischemic stroke in territory of stenotic artery = 12% in ASA, 11% in warfarin Factors associated with increased risk of recurrent stroke (WASID) Severe stenosis ( 70%); HR=2.03 Enrolled early ( 17 days); HR=1.69 Female gender; HR=1.59 HTN (sbp 140 mmhg); HR=1.79 Cholesterol ( 200 mg/dl); HR=1.44 Blacks with ICAD have higher risk of recurrent stroke than whites (25% vs. 16%). No data on Asians WASID Location of stenosis and type of event were not associated with an increased stroke risk Failed anti-thrombotics thrombotics do not have higher stroke risk Co-existing asymptomatic intracranial stenoses (50-99%) have low risk of stroke 8

9 TOSS-2 Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II Hong Kong, Korea, Philippines, Thailand, 480 patients >35 y.o. with symptomatic M1 or basilar Cilostazol + 100mg ASA vs. Clopidogrel mg ASA Outcome: progression rate on MRA Angioplasty Cochrane Collaboration 2006 review No randomized trials 79 articles with open-label case series 3 cases Perioperative stroke rate 7.9% (CI ) Periop death rate 3.4% (CI ) No comments could be made on effectiveness Insufficient data to recommend angioplasty Stenting SSYLVIA: Neurolink bare metal stent, 95% success rate, 32.4% in-stent 6 mos, 13.1% ischemic 12 mos Drug eluting stent: retrospective review, 90% success rate, 5% of re-stenosis rate intracranially at 4±2 months Wingspan self expanding intracranial stent (FDA approved): single arm study, 97.7% success rate, 7.5% in-stent 6 mos, all asymptomatic, 7% ipsilateral stroke or death 6 mos SAMMPRIS Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis NIH sponsored, randomized, multi-center Patients with a TIA or stroke within 30 days prior to enrollment & 70-99% stenosis of a major intracranial artery on angio Randomize to aggressive med rx vs. intracranial stenting (Wingspan) & aggressive medical rx Possible patient recruitment starting at UCSF in Spring

10 Summary ICAD is under-recognizedrecognized Higher prevalence among Asians High recurrent stroke rate despite medical therapy Need: Fast, readily available, reliable, minimally invasive diagnostic methods Better predictors of clinical outcomes Better predictors of progression or regression of disease Better treatment options Case #1 60 y.o. Chinese-speaking speaking woman h/o anxiety/depression, HTN, c/o HAs. PCP obtained a MRI/MRA brain. Found several areas of significant intracranial athero. Refer to Neuro Meds: HCTZ What to do next? a) Start antiplatelet b) Start coumadin c) Start a statin d) Refer to NIR for angioplasty/stenting e) Get a diagnostic catheter angiogram f) Get CTA Case #2 66y.o. Filipino man h/o HTN, DM, presented with left sided weakness. Found on CT/CTA to have intracranial occlusion of right M2, severe (70-80%) bilateral vertebral stenoses. Meds: lisinopril, HCTZ, glucophage, ASA What to do next? a) Add Clopidogrel to ASA b) switch to Clopidogrel alone c) Switch to Aggrenox d) Start a statin e) Refer to NIR for angioplasty/stenting of vertebral arteries Thank you! UCSF Neurovascular Faculty Wade Smith, Director of Neurovascular S. Claiborne Johnston, Director of Stroke Service Claude Hemphill, Director of Neuro SFGH Vineeta Singh Nerissa Ko Andy Josephson Anthony Kim 10