10/4/18 Acute Ischemic Stroke in the Emergency Department Robert L. Alunday, MD Assistant Professor Departments of Neurosurgery and Emergency Medicine Medical Director, Neurosciences ICU University of New Mexico No financial disclosures 1
10/4/18 Objectives 1. Review types of strokes 2. Indications and contra-indications for alteplase 3. Indications for Thrombectomy 4. Emergency Department Systems of Care The Problem 2
10/4/18 Nationally 795,000 Annually 1 every 40 seconds Stroke kills every 4 minutes $34 billion each year https://www.cdc.gov/stroke/facts.htm Three types of stroke Case courtesy of Dr Frank Gaillard, radiopaedia.org Case courtesy of Dr David Cuete, Radiopaedia.org, rID: 22770 https://sites.google.com/a/wisc.edu/neuroradiology/image- acquisition/vascular-imaging/mr-angiography 3
10/4/18 SAH treatment SBP<140, until secured IPH treatments BP control? Surgery Minimally invasive surgery 4
10/4/18 MISTIE II trial Hanley Lancet Neurol. 2016 November ; 15(12): 1228–1237 5
10/4/18 MISTIE II Two types of ischemic strokes http://resusreview.com/wp- https://www.ev3.net/assets/007/5793.jpg content/uploads/2013/05/Alteplase_Mixing_Procedur e_9.jpg 6
10/4/18 Why Time is Brain There is a difference between Infarction and Ischemia You can’t help infarcted brain 7
10/4/18 1.9 million neurons lost each minute a stroke is not treated Saver. Stroke 2006;37:263-266 8
10/4/18 Why Time is Brain https://med.stanford.edu/neurology/divisions/stroke/research1.html tPA administered within 3 hours of stroke onset decreased Death or dependency (mRS 3-6) Wardlaw et al. Cochrane Database (review) 2014 9
10/4/18 Time is brain Pooled analysis of 3670 pts from ECASS I, II, III, ATLANTIS, NINDS, and EPITHET trials Lees et al. Lancet 2010; 375:1695-1703 Inclusion/exclusion for alteplase Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke. Stroke. 2016 Feb;47(2):581-641 10
10/4/18 Inclusion criteria Diagnosis of ischemic stroke causing measurable neurological deficit Onset of symptoms <3 h before treatment begins Age ≥ 18 y Exclusion criteria Significant head trauma or prior stroke in the previous 3 mo Symptoms suggest SAH Arterial puncture at noncompressible site in previous 7 d History of previous intracranial hemorrhage Intracranial neoplasm, AVM, or aneurysm Recent intracranial or intraspinal surgery Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg) Active internal bleeding Acute bleeding diathesis, including but not limited to Platelet count <100 000/mm3 Heparin received within 48 h resulting in abnormally elevated aPTT above the upper limit of normal Current use of anticoagulant with INR >1.7 or PT >15 s Current use of DOAC’s with elevated sensitive laboratory tests (eg, aPTT, INR, platelet count, ECT, TT, or appropriate factor Xa activity assays) Blood glucose concentration <50 mg/dL (2.7 mmol/L) CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere) Relative exclusion criteria 11
10/4/18 Relative exclusion criteria Only minor or rapidly improving stroke symptoms (clearing spontaneously) Pregnancy Seizure at onset with postictal residual neurological impairments Major surgery or serious trauma within previous 14 d Recent gastrointestinal or urinary tract hemorrhage (within previous 21 d) Recent acute myocardial infarction (within previous 3 mo) FDA contraindication Current intracranial hemorrhage Subarachnoid hemorrhage Active internal bleeding Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma Presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms) Bleeding diathesis Current severe uncontrolled hypertension. 12
10/4/18 Endovascular trials of 2015 summary of studies (protocols) time to groin NIHSS for NIHSS time from Additional puncture n IV-tPA use (min) Median inclusion Median (IQR) Stroke onset Imaging (IQR) 260 (210- 500 >1 MR CLEAN 17 (14-21) 6 hours not required CTA 313) 185 (116- 316 >6 ESCAPE 16 (13-20) 12 hours not required multiphasic CTA 315) EXTEND- 210 (166- 70 none 17 (13-20) 6 hours required CTA and CTP IA 251) SWIFT 196 8-29 CTA/PCT 17 (13-20) 6 hours 184 required PRIME or MRA/DWI/PWI 269 (201- 206 >6 REVASCAT 17 (12-19) 8 hours not required CTA 340) 13
10/4/18 summary of study (results) MORTALITY mRS %mRS 0-2 TICI 2b/3 symptomatic ICH 3 / 4 18.9% / 18.4% 58.7% 33% / 19% MR CLEAN 7.7% / 6.4% at 30 days 2 / 4 72.4% 53% / 23% ESCAPE 10% / 19% 3.6% / 2.7% 1 / 3 86% 70% / 40% EXTEND IA 9% / 20% 0% / 6% 88% 2 / 3 SWIFT PRIME 9% / 12% 5.1% / 7.2% 60.1% / 35.5% 18.4%/15.5% 65.7 REVASCAT 43.7% / 28.2% 4.9% / 1.9% at 90 days Why were these trials successful? Imaging base evidence of large vessel occlusion Imaging-based exclusion of patients with a large core Newer and better device (TICI 2b/3 of 25%-41% on early generation IAT vs 59-88% with stent retriever) 14
10/4/18 Meta-analysis on Thrombectomy for Stroke NNT to reduce mRS by 1 point: 2.6 NNT to get to mRS 0-2: 6 NNT for PCI for STEMI to prevent long term death: 29 Lancet 2016; 387: 1723–31 Circulation. 2009; 119: 3101-3109 JAMA . 2016;316(12):1279-1288 15
10/4/18 Traditional Indications for Thrombectomy New stroke symptoms beginning within: 6 hours (anterior circulation, ICA, MCA) 12 hours (posterior circulation, basilar artery) Pre-stroke modified Rankin Scale 0 – 3 NIH Stroke Scale Score 6 or higher CT head with NO evidence of hemorrhage ASPECT score 6 – 10 CTA with occlusion of ICA or MCA (horizontal segment or proximal first vertical segment) or basilar artery that correlates with new stroke symptoms Endovascular trials of 2017/2018 16
10/4/18 The DAWN Trial Published Nov 11, 2017 The DAWN Trial 206 patients enrolled (planned for 500) Multicenter, prospective, RCT, Bayesian adaptive-enrichment design, and blinded assessment of endpoints Industry sponsored Authors had unrestricted access to the data analysis was performed by data-management staff from Styker, with oversight from independent statisticians 17
10/4/18 Missmatch (clinical symptoms vs imaging core infarct) LVO present Age >80, NIHSS >10, Infarct <21ml Age <80, NIHSS >10, Infarct 21-31ml Age <80, NIHSS >20, Infarct 31-51ml 18
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10/4/18 DEFUSE 3 Published Jan 24, 2018 Missmatch If NCCT done, ASPECT score >6 Infarct core <70ml Ratio of ischemia to infarction of 1.8 Absolute volume of penumbra of 15ml 20
10/4/18 DEFUSE 3 Sponsored by the NIH Any FDA thrombectomy device was used 21
10/4/18 Results Enrolled 182/476 patients, but stopped early in light of DAWN trial results (Per NIH) 22
10/4/18 DAWN NNT = 3 DEFUSE NNT = 4 23
10/4/18 Lessons from 2017/2018 You can help some patients in the 6-24 hour window Advanced imaging necessary Indications for thrombectomy in the 6- 24 hour time frame New stroke symptoms beginning within 6 – 24 hours (anterior circulation = ICA or MCA only; Does not include basilar artery) Pre-stroke modified Rankin Scale 0 – 3 CT head with NO evidence of hemorrhage MRA or CTA with occlusion of ICA or MCA (horizontal segment or proximal first vertical segment) Infarct core on DWI or CBV less than 70 ml Ratio of 1.8 of ischemic tissue to infarcted tissue (perfusion mismatch) Tmax greater than 6 seconds/ADC i. ADC less than 620 Tmax greater than 6 seconds /CBV Only if CBV is less than 30% 24
10/4/18 Coordinated System of Care in the ED 25
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10/4/18 Breaking News 27
10/4/18 N Engl J Med 2018; 379:611-622 WAKE-UP Trial 503 patients enrolled Alteplase vs standard care 70 centers in 8 European countries Last Known well >4.5 hours to infinity, but symptom recognition within 4.5 hours Early stroke based on MRI (DWI+ and FLAIR-) 28
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10/4/18 Take home points TIME IS BRAIN Alteplase is given more often than FDA indicates Advanced imaging is becoming critical Team approach (nursing, EM, stroke neurologists, radiology, pharmacy) is the only way to diagnose and treat timely 30
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