Acute Ischemic Stroke in the Emergency Department No financial - PDF document

10/4/18 Acute Ischemic Stroke in the Emergency Department No financial disclosures Robert L. Alunday, MD Assistant Professor Departments of Neurosurgery and Emergency Medicine Medical Director, Neurosciences ICU University of New Mexico Objectives 1. Review types of strokes The Problem 2. Indications and contra-indications for alteplase 3. Indications for Thrombectomy 4. Emergency Department Systems of Care Nationally Three types of stroke 795,000 Annually 1 every 40 seconds Stroke kills every 4 minutes $34 billion each year https://www.cdc.gov/stroke/facts.htm 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 1

10/4/18 SAH treatment IPH treatments SBP<140, until secured BP control? Surgery Minimally invasive surgery MISTIE II trial Hanley Lancet Neurol. 2016 November ; 15(12): 1228–1237 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 2

10/4/18 Why Time is Brain There is a difference between Infarction and Ischemia You can’t help infarcted brain 1.9 million neurons lost each minute a stroke is not treated Saver. Stroke 2006;37:263-266 tPA administered within 3 hours of stroke onset Why Time is Brain decreased Death or dependency (mRS 3-6) Wardlaw et al. Cochrane Database (review) 2014 https://med.stanford.edu/neurology/divisions/stroke/research1.html 3

10/4/18 Time is brain Inclusion/exclusion for alteplase Pooled analysis of 3670 pts from ECASS I, II, III, ATLANTIS, NINDS, and EPITHET trials Scientific Rationale for the Inclusion and Exclusion Criteria Lees et al. Lancet 2010; 375:1695-1703 for Intravenous Alteplase in Acute Ischemic Stroke. Stroke. 2016 Feb;47(2):581-641 Exclusion criteria Inclusion 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 Diagnosis of ischemic stroke causing measurable neurological deficit Recent intracranial or intraspinal surgery Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg) Active internal bleeding Onset of symptoms <3 h before treatment begins Acute bleeding diathesis, including but not limited to Platelet count <100 000/mm3 Age ≥ 18 y 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 Relative exclusion criteria FDA contraindication Current intracranial hemorrhage Only minor or rapidly improving stroke symptoms (clearing spontaneously) Subarachnoid hemorrhage Pregnancy Active internal bleeding Seizure at onset with postictal residual neurological impairments Major surgery or serious trauma within previous 14 d 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., Recent gastrointestinal or urinary tract hemorrhage (within previous 21 d) some neoplasms, arteriovenous malformations, or aneurysms) Recent acute myocardial infarction (within previous 3 mo) Bleeding diathesis Current severe uncontrolled hypertension. 4

10/4/18 summary of studies (protocols) time to groin NIHSS for NIHSS time from Additional puncture n IV-tPA use inclusion Median (IQR) Stroke onset Imaging (min) Median (IQR) 260 (210- Endovascular trials of 2015 500 >1 MR CLEAN 17 (14-21) 6 hours not required CTA 313) 185 (116- ESCAPE 316 >6 16 (13-20) 12 hours multiphasic CTA not required 315) EXTEND- 210 (166- 70 none 17 (13-20) 6 hours required CTA and CTP IA 251) SWIFT CTA/PCT 196 8-29 17 (13-20) 6 hours 184 required PRIME or MRA/DWI/PWI 269 (201- REVASCAT 206 >6 17 (12-19) 8 hours CTA not required 340) summary of study (results) Why were these trials successful? MORTALITY mRS %mRS 0-2 TICI 2b/3 symptomatic ICH 18.9% / 18.4% 3 / 4 58.7% 33% / 19% 7.7% / 6.4% MR CLEAN at 30 days Imaging base evidence of large vessel occlusion 2 / 4 72.4% 53% / 23% ESCAPE 10% / 19% 3.6% / 2.7% Imaging-based exclusion of patients with a large core 1 / 3 86% EXTEND IA 9% / 20% 70% / 40% 0% / 6% Newer and better device (TICI 2b/3 of 25%-41% on early generation IAT vs 59-88% with stent retriever) 2 / 3 88% 60.1% / 35.5% SWIFT PRIME 9% / 12% 5.1% / 7.2% 18.4%/15.5% 65.7 REVASCAT 43.7% / 28.2% 4.9% / 1.9% at 90 days 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 5

10/4/18 Traditional Indications for Thrombectomy New stroke symptoms beginning within: 6 hours (anterior circulation, ICA, MCA) 12 hours (posterior circulation, basilar artery) Endovascular trials of 2017/2018 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 The DAWN Trial 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 Published Nov 11, 2017 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 6

10/4/18 DEFUSE 3 Missmatch If NCCT done, ASPECT score >6 Infarct core <70ml Ratio of ischemia to infarction of 1.8 Absolute volume of penumbra of 15ml Published Jan 24, 2018 DEFUSE 3 Sponsored by the NIH Any FDA thrombectomy device was used 7

10/4/18 Results Enrolled 182/476 patients, but stopped early in light of DAWN trial results (Per NIH) DAWN NNT = 3 DEFUSE NNT = 4 Indications for thrombectomy in the 6- Lessons from 2017/2018 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 You can help some patients in the 6-24 hour window 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 Advanced imaging necessary 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% 8

10/4/18 Coordinated System of Care in the ED Breaking News 9

10/4/18 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-) N Engl J Med 2018; 379:611-622 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 10