Management and Investigation of Ischemic Stroke By Etiology Andrew M. Demchuk MD FRCPC Director, Calgary Stroke Program Deputy Dept Head, Clinical Neurosciences Heart and Stroke Foundation Chair in Stroke Research Professor Depts Clinical Neurosciences and Radiology Hotchkiss Brain Institute University of Calgary
Recurrent Stroke Rates
Stroke Care Continuum Primary Prevention Stroke Onset EMS Transport ED Time Stroke Team Assessment Imaging Acute Treatment Reintegration Rehabilitation Clinical Worsening/ Complication Prevention Admission Secondary Prevention 3
Standard Workup for Ischemic Stroke
Ischemic stroke?/esus Cardioembolic Large artery Small vessel Other
Ischemic stroke?/esus Cardioembolic Large artery Small vessel Other
Vascular imaging Important in young stroke too!
Ischemic stroke Cardioembolic Large artery Small vessel Other/?
Atherosclerosis affects multiple vascular beds Large Artery Cerebrovascular disease Coronary artery disease
Transcranial Doppler Emboli Detection
Two Carotid Revascularization Options >50% symptomatic ICA stenosis CEA CAS vs
NNT 3-7
Up to 5% in first 5 days
CAS vs CEA trials
Better worse CAS vs CEA trials CEA better CAS better CAS better
Intracranial (medium sized) atherosclerosis MCA stenosis
Intracranial stenting not safe ASA+clopidogrel X 1 month; high dose statins; exercise program
Large Artery Atherosclerosis and dual antiplatelets
Large Artery Athero Stroke benefits from statins NNT 20
Ischemic stroke Cardioembolic Large artery Small vessel Other/?
DWI MRI Single penetrating infarct
Hypertensive arteriolosclerosis Multiple lumena (*) Patent arteriole Segmental arteriolar occlusion * * * * Glomeruloid arteriole Lacune Smooth muscle hyperplasia smooth muscle cell loss tunica media Inward disease causes lacunar stroke
Hypertensive arteriolosclerosis Hemosiderin Outward disease causes ICH
High dose Atorvastatin use in arteriolosclerosis increased ICH Neurology 2008;70:2364-70 4 fold increase in ICH with high dose atorvastatin!
Key Messages: Tailored Secondary Prevention Stroke or TIA determine etiology then focus treatment Other/unusual Management varies widely by etiology Dissections and arteriopathies most common Large artery atherosclerosis (CT-angio or MRA) short course of ASA/clopidogrel at least high dose statins; treat to target LDL<2 revascularization if >50% cervical ICA stenosis and early after event Intracranial stenosis stenting not safe Small vessel disease (arteriolosclerosis) (MRI) Aggressive blood pressure control to target most NB- lower better Avoid high dose statins Single antiplatelets long term
Case 1 Age 45, no afib, no cerebrovascular risk factors moderate sized cortical stroke- minimal deficits CTA head/neck normal Echo normal TEE normal
No Cause Found Common Especially in Young Stroke
PFO stroke eligible
Case 1b Age 45, no afib, no cerebrovascular risk factors moderate sized L cortical stroke- minimal deficits CTA head/neck left cervical carotid web TTE normal
8.9% carotid web young cryptogenic stroke 1.9% carotid web age matched controls
Web Its Not So Cryptogenic Anymore
Case 1c Age 45, no afib, no cerebrovascular risk factors moderate sized cortical stroke- minimal deficits CTA head/neck normal TTE small PFO TEE PFO confirmed
GORE
Very Clear Benefit in Stroke Prevention With PFO Closure Overall
Who Should Get PFO Closure? Younger patients more benefit
Who Should Get PFO Closure? Moderate/large shunts more benefit Large shunts more strokes with medical mgmt
Who Should Get PFO Closure? Only Antiplt group benefited from closure AC vs AP
Who Should Get PFO Closure? Very high D Dimer predicts high stroke risk <700 >700
Role for Anticoagulation in PFO stroke?
Role for Anticoagulation in PFO stroke in elderly? Only Antiplt group benefited from closure
TCD Bubble Study Best To Evaluate Shunt Size
Its Not So Cryptogenic Anymore Web PFO
PFO Closure Pathway ESUS TCD bubble: moderate/large shunt <60 years old Requires anticoagulation AC stopped Arrange TEE for PFO characteristics 3 month followup with family to confirm interest in closure Referral to structural heart clinic for interventional cardiology decision on closure
Case 2 Age 69, no known afib, stomach cancer moderate cortical stroke CTA head/neck normal Echo normal TEE normal What test should you order?
Very Elevated D-dimer > 2 microg/ml = cancer
D-dimer falls further with LMWH than with warfarin
Its Not So Cryptogenic Anymore Web PFO Cancer Associated Thrombosis
Case 3 Age 77, no known afib, cerebrovascular risk factors Prior cortical infarct moderate cortical stroke CTA head/neck normal Echo left atrium mild enlargement Holter 1003 APBs/24h
Yield of Prolonged Rhythm Monitoring
Case 3 Age 77, no known afib, cerebrovascular risk factors Prior cortical infarct moderate cortical stroke CTA head/neck normal Echo left atrium mild enlargement Holter 1003 APBs/24h 28 day monitor: several <1 minute runs of atrial fibrillation
>24h duration SCAF
Its Not So Cryptogenic Anymore Web PFO Cancer covert AF Associated Thrombosis
Case 4 Age 77, no known afib, coronary artery disease Prior cortical infarct moderate cortical stroke Echo: moderate LV dysfunction with Apical and lateral hypokinesis
Largest stroke prevention effect if prior stroke Outcome Rivaroxaban plus Aspirin (N=9152) Aspirin (N=9126) Rivaroxaban plus Aspirin vs. Aspirin N Pts %/yr N Pts %/yr HR (95% CI) P P inter Stroke 0.40 No Previous Stroke Previous Stroke 8801 351 0.4 0.7 8791 335 0.7 3.4 0.60 (0.45-0.80) 0.42 (0.19-0.92) 0.0006 0.03 Ischemic or uncertain stroke 0.28 No Previous Stroke Previous Stroke 8801 351 0.4 1.1 8791 335 0.7 3.4 0.54 (0.40-0.74) 0.33 (0.14-0.77) 0.0001 0.01 Previous stroke ARR = 2.7% NNT = 37 www.phri.ca 14
Cryptogenic/ESUS Strokes Many Considerations Summary Web PFO Cancer covert AF minor cardiac Associated Thrombosis
Cardioembolic Stroke has worst outcome
Echo yields warfarin indicated etiologies
Atrial Fibrillation Atrial fibrillation (AF) is the most common heart rhythm disturbance It is estimated that 1 in 4 individuals aged 40 will develop AF in their lifetime AF=atrial fibrillation Normal rhythm AF Lloyd-Jones DM, et al. Circulation 2004;110:1042-1046
Stroke Outcome in Patients with AF Effect of first ischemic stroke in patients with AF (n=597) 60% 50% 60% 40% Percent of patients 30% 20% 10% 0% -10% Disabling 20% Fatal 1. Gladstone DJ et al. Stroke 2009; 40:235-240
Atrial fibrillation can produce large emboli
Anticoagulation in Atrial Fibrillation Thromboembolic Risk Reduction
Direct oral anticoagulants (DOACs) Apixaban Edoxaban Dabigatran
GI Bleeding Common Early - Unmasks GI Cancer Recommend occult blood testing, Hb test: 2-4 weeks early after initiation***
Case 5 Age 71 male, afib embolic stroke on warfarin INR 2.5; GFR >60
Dabigatran 150 bid best to prevent stroke
Case 6 Age 71 male, afib, mechanical aortic valve embolic stroke on warfarin INR 2.5; GFR >60
Case 7 Age 75 female, afib, Htn, smoker, Needs carotid stenting for symptomatic ICA stenosis
Triple tx Very low dose Riva +DAPT WOEST like Riva 15+P2Y 12
Very low dose Riva +DAPT
Case 8 Age 79 male, afib for 15 years on warfarin stable INRs brief episode of numbness to left hand
Stable on warfarin
Case 9 Age 82 female, afib for 5 years independent,well, GI bleed 10 years ago TIA (aphasia X 5 minutes)
Apixaban safe in the elderly
Apixaban dosing
Edoxaban safe in the elderly % dose reduced over 75 yrs old
Case 10 Age 90 female, afib for 20 years, suffers cortical infarct,moderate dementia nursing home, very limited quality of life
Afib OAC choices after stroke Characteristic Choice High-risk for stroke Dabigatran 150 GERD sx, prior MI/CAD, low GFR Mechanical valve Coronary/carotid stenting Stable on warfarin Elderly Very frail/dependent/poor QOL Riva or Apixa Warfarin +/- ASA NO MORE TRIPLE TX Warfarin + clopidogrel 2.5 bid Riva + DAPT 15 Riva + clopidogrel Continue warfarin esp if questionable new event Apixaban/Edoxaban Consider no treatment
Thank-you for your attention! Email me if you need anything: ademchuk@ucalgary.ca