Clinical Decision Making: Hyperacute Management of Symptomatic Carotid Artery Disease

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Clinical Decision Making: Hyperacute Management of Symptomatic Carotid Artery Disease Tarvinder Singh, MS, MD Neurohospitalist Swedish Neuroscience Institute 1

Objectives Definition Why the urgency? Evidence/Guidelines for symptomatic carotid disease (BP, antithrombotics, CEA/CUS) Special situations: Role of heparin Role of acute endovascular management CEA/CUS in women, elderly, while on DAP, with disabling stroke, timing 2

Case 58 year-old right-handed woman woke up with new left-sided weakness. PMHX: Diabetes, Hypertension, Hyperlipidemia, TIA 2 years ago. SHX: No bad habits. Home Meds: ASA 81mg daily. No statin. Exam: BP 160/90, CN intact. Left hand and entire leg strength 4/5. Walks without support. Labs: LDL 122, A1c 7.0 3

Case: 58yo with left-sided weakness CT/H without acute changes CTA with R ICA 80% stenosis (NASCET criteria), L ICA < 50%, and diffuse mild atherosclerotic disease. Next steps? 4

Case: 58yo with left-sided weakness MRI with peri-rolandic R frontal ischemic stroke, about 10 cc in volume. Started on aspirin 81mg daily and clopidogrel 75mg daily Admitted to the neurology floor with acute ischemic stroke order set and frequent neuro checks. Next steps? 5

What is the urgency? Why close monitoring, further diagnostics and urgency of intervention? 6

Risk of recurrent TIA/stroke after event is front loaded. > 2000 pts with ischemic stroke. Of those, > 500 with prior TIA events. Of strokes preceded by TIA, 43% of strokes happened in first 7 days after TIA. Third of those happened on the day of stroke! Timing of TIAs preceding stroke: Time window for prevention is very short. Neurology 2005. Timing of TIAs preceding stroke: Time window for prevention is very short. Neurology 2005. 7

The second event was disabling or fatal in half of these patients. Fairhead JF, Mehta Z, Rothwell PM. Population-based study of delays in carotid imaging and surgery and the risk of recurrent stroke. Neurology. 2005;65:371 375 8

Risk of stroke in the hyperacute period after the index TIA in patients with 50 99% carotid stenosis compared with pooled data from the randomized trials. 48 h 72 h 7 d 14 d 5 y ESCT + NASCET + VA (medical therapy) 2 21% Fairhead et al. (2005) 29 20% Purroy et al. (2007) 30 10% Ois et al. (2009) 31 17% 22% 25% Bonifati et al. (2011) 32 8% Johansson et al. (2013) 33 5% 8% 11% Merwick et al. (2013) 34 8% Marnane et al. (2014) 35 5% 9% 9% 16% b Source: Naylor, European Journal of Vascular and Endovascular Surgery June 2015 9

Why is early stroke risk high? CEA performed < 4 weeks of index TIA > 4 weeks Thrombus overlying plaque 66% 21% Naylor, Review Time is Brain 2015; [Harrison, Marshall 1977] 10

However, not everyone with TIA or minor stroke ends up with a stroke. Can high-risk patients be identified? Would they be treated differently? 11

Transcranial doppler Prevalence of spontaneous emboli on TCD after symptom onset: 42% of patients in < 7 days 22% 8-14 days 16% > 14 days Salem MK, Sayers RD, Bown MJ, Naylor AR. Spontaneous embolisation in asymptomatic and acutely symptomatic patients with TIA/ minor stroke. Eur J Vasc Endovasc Surg 2011;41:720-5. 12

MRI of carotid plaque Axial views of T1-weighted water-selective magnetic resonance imaging to detect plaque hemorrhage of carotid arteries. Hyperintense signals (B D, white arrows) reflect plaque hemorrhage in carotid arteries, black arrows (A) show absence of plaque hemorrhage, and asterisks indicate the lumen of internal carotid artery. (A) No signal hyperintensity. (B) Large moderately hyperintense plaque. (C) Small strongly hyperintense plaque. (D) Large strongly hyperintense plaque. 13

Intraplaque hemorrhage predicts outcome Hosseini et al: Carotid Plaque Hemorrhage 2013 14

Management 15

Blood pressure Current consensus guidelines recommend treating BP > 220/120 mmhg unless patient has received thrombolytic therapy in which case the maximum permitted BP is 185/110 mmhg. However, hyperacute post-stroke BP often has to be individualized. 16

Anti-platelet therapy ASA + Clopidogrel > 50% reduction in microemboli POINT trial ongoing. SOCRATES trial ticagrelor 90mg BID vs ASA 100mg QD after stroke/tia with no significant benefit. However, subgroup analysis showed benefit if ipsilateral carotid disease. Ischemic CVA, MI, Death Ischemic CVA SOCRATES, Lancet 2017 17

TARDIS Anti-platelet triple therapy no benefit over dual therapy More bleeding POINT trial for further data on DAPT The Triple Antiplatelets for Reducing Dependency in Ischemic Stroke (TARDIS) trial, 2017 18

Case: 58yo with left-sided weakness Additional diagnostics TCD w/ emboli monitoring Carotid ultrasound/mri to characterize the carotid plaque Additional management CEA/CAS Heparin gtt 19

CEA 20

CEA - Timing Naylor, Review Time is Brain 21

CEA - Gender Naylor, Review Time is Brain 22

CEA Most of the data is based on old medical therapy, TIA/minor stroke and high peri-procedural risk. Current guidelines recommend periprocedural risk of stroke/death < 6% for symptomatic carotid stenosis. Suggested that this be lowered to < 2%. Favors medical mgmt. Favors surgery Sex Female Male Lesion Smooth Ulcerated Sx type Retinal Hemispheric Collaterals Present Absent Comorbidity Present Absent Chaturvedi S, Emergency Medicine 2000 23

Hyperacute CEA How early can we safely do CEA? 24

Procedural risk of CEA w.r.t. to timing [15 SwedVasc Registry] Very urgent carotid endarterectomy confers increased procedural risk Stroke, 43 (2012), pp. 1331 1335 [16] Procedural risk following carotid endarterectomy in the hyperacute period after onset of symptoms Eur J Vasc Endovasc Surg, 46 (2013), pp. 519 524 [17] Very urgent carotid endarterectomy does not increase the procedural risk Eur J Vasc Endovasc Surg, 49 (2015), pp. 129 136 25

26

Why lower procedural risk in Leicester study? we attributed our very low procedural risks to an obsessional attention to surgical technique, completion angioscopy/intraoperative TCD, peri-operative dual antiplatelet therapy and written guidelines for treating post-cea hypertension. 27

CEA - Elderly Depends on life expectancy. There is post-operative risk and that benefit recouped over the years. However, if they are not alive long, then that benefit cannot be recuperated. 28

Debatable Heparin for acute ischemic stroke Severe stroke patients excluded form trials. Would they benefit from intervention? 29

Case 75 year old woman with no PMHx woke up with left side weakness. On exam: Left hemiparesis and neglect EKG: normal Symptoms: progressing What antithrombotic medication would you want to use acutely? 30

Aspirin 31

Heparin 32

33

Miller Fisher: The Master of Clinicopathologic Correlation. Interview Trobe, Jonathan D. MD JDT: And weren t you responsible for introducing the idea of anticoagulation in TIAs and large extracranial artery stenosis? CMF: Yes. The first patient I anticoagulated with heparin had basilar TIAs. We d turn on the heparin and the TIAs would stop, turn it off and they d start up again. I set up the first anticoagulation trial. Seven centers cooperated. We had so many fatal bleeding accidents that it appeared unlikely that a benefit could be shown. http://mobile.journals.lww.com/jneuroophthalmology/fulltext/2004/03000/c Miller_Fisher The_Master_of_Clinicopathologic.14.aspx 34

Multiple trials in use of heparin IST (unfractionated sq heparin) TOAST (danaproid) FisBis (fraxiparin) HAEST (dalteparin) NO overall benefit. 35

Anticoagulation for acute ischemic stroke Guidelines do not support routine use of anticoagulation post-stroke. However, experts consider it in : Conditions with potential high risk of early cardiogenic reembolization Symptomatic dissection of the arteries supplying the brain Symptomatic extracranial or intracranial arteriosclerotic stenosis with crescendo TIAs or early progressive stroke TCDs with embolization/stump Basilar artery occlusion before or after intra-arterial pharmacological or mechanical thrombolysis. Known hypercoagulable states Cerebral venous sinus thrombosis 36

Conclusion Post-stroke/TIA recurrence stroke rate is high. Evidence/Guidelines exist for symptomatic carotid disease (BP, antithrombotics, CEA/CUS) Identification of high-risk patients can allow targeted therapies such as hyperacute CEA and anticoagulation. Women have a different risk/benefit profile. 37

Extra slides 38