Diagnosis and Management of Acute Stroke in 2017

Transcription

1 Diagnosis and Management of Acute Stroke in 2017 Jeffrey A. Switzer, DO, MCTS, FAHA Professor Director, Telestroke and Teleneurology Director, Comprehensive Stroke Center Department of Neurology Medical College of Georgia Augusta University

2 Contents Background Clinical Evaluation and Neuroimaging Summary of Benefits/Risks of IV rt-pa The Code Stroke and Door-to-tPA efficiency Summary of Benefits/Risks of Endovascular Revascularization

3 Background 1. Heterogenous (but syndromic) presentations determined by vascular territory commonly hemiparesis, facial weakness, speech and/or language dysfunction LVO (large vessel occlusion) stroke vs NLVOS No EKG or biomarker Diagnosis is clinicalradiographic

4 Background 2. Viability of ischemic tissue downstream from the occlusion is dependent upon the severity and duration Infarct Core Penumbra Benign Oligemia Goal of acute treatment is to safely re-establish blood flow while tissue is still viable

5 Collateral in the setting of ischemic stroke can reduce infarct size and is a mechanism for sustained cerebral perfusion in the setting of an acute occlusion

6 Background 3. Reperfusion is the only effective strategy in acute ischemic stroke a. IV rt-pa is the only established effective pharmacologic treatment for acute ischemic stroke b. More recently, stent retrievers have demonstrated efficacy <10% of stroke patients are candidates for endovascular treatment Oversimplified Why shouldn t I recommend tpa now? Why shouldn t this patient be considered for endovascular therapy

7 Background 4. Irreversible ischemic brain injury occurs rapidly Stroke. 2006; 37:

8 Odds ratio (95% CI) Background 5. The efficacy of recanalization is highly timesensitive Interaction: 2 1=5 80 (p=0 016) Alteplase (n=3391) Control (n=3365) Odd (95% Treatment delay 3 0 h 259/787 (32 9%) > h 485/1375 (35 3%) >4 5 h 401/1229 (32 6%) Age (years) /2512 (39 4%) >80 155/879 (17 6%) Baseline NIHSS score /345 (68 7%) /1281 (47 7%) /794 (24 9%) /662 (11 6%) 22 22/309 (7 1%) 176/762 (23 1%) 432/1437 (30 1%) 357/1166 (30 6%) 853/2515 (33 9%) 112/850 (13 2%) 189/321 (58 9%) 538/1252 (43 0%) 175/808 (21 7%) 55/671 (8 2%) 8/313 (2 6%) Treatment delay (h) Alteplase worse Alteplase better Figure 1: Effect of timing of alteplase treatment on good stroke outcome (mrs 0 1) The solid line is t between the log odds ratio for a good stroke Lancet 2014; 384: Circulation. 2016;133:

9 Background 6. The efficacy of IV rt-pa is site specific Proximal (large volume) clots are unlikely to recanalize IMS-3 tpa only ICA occlusion M1 occlusion M2 occlusion % Recanalization at 24 hours

10 Evaluation Ischemic stroke is a clinicoradiologic diagnosis The diagnosis of stroke is often missed The diagnosis of stroke is often confused with a stroke mimic Key clinical features of Ischemic Stroke Acute onset Focal (unilateral) neurologic deficit(s) potentially localizing to a cerebral vascular territory Normal level of alertness Absence of headache Absence of seizure activity The Recognizable Pattern - Hemiparesis, facial droop and speech or language disturbance are the most sensitive and have highest PPV

11 Evaluation What else could it be? Common Ischemic Stroke Mimics Neurologic Seizure/post-ictal state Subarachnoid Hemorrhage Subdural Hematoma Intraparenchymal Hemorrhage Cerebral Abscess Brain Tumor Multiple Sclerosis Encephalitis Bell s Palsy Vestibular Neuronitis Hypertensive Encephalopathy Migraine Metabolic Hypo/Hyperglycemia Hepatic Encephalopathy Drug Overdose Psychiatric Conversion Disorder Malingering Other Syncope Acute Coronary Syndrome

12 Evaluation - History Do the symptoms suggest stroke? Time of onset Still drives stroke treatment decision-making (IV tpa) Surrogate for tissue viability Witnessed onset, wake-up or found impaired Last known well Time of symptom discovery

13 Evaluation - Exam Vital Signs BP Neurologic Examination National Institutes of Health Stroke Scale (NIHSS); most widely used in acute settings Scale from 0-42; quantify neurologic deficit Predictor of neurologic outcome at one year NIHSS<10 62% chance of favorable outcome NIHSS>20 4% chance of favorable outcome Kwiatkowski TG, et al. NEJM 1999;340: LOC (0-7) 2. Best gaze (0-2) 3. Visual Fields (0-3) 4. Facial Paresis (0-3) 5. Arm Motor (0-4 x 2) 6. Leg Motor (0-4 x 2) 7. Limb Ataxia (0-2) 8. Sensory (0-2) 9. Extinction/Inattention (0-2) 10. Dysarthria (0-2) 11. Language (0-3) * Higher NIHSS (>8), gaze deviation, aphasia, and neglect increase the likelihood of LVO

14 Evaluation - Labs Emergency Laboratory Evaluation CBC, BMP, PT/PTT/INR Cardiac enzymes, UDS, EtOH level, BHCG in selected cases No identified serum marker for ischemic stroke with suitable diagnostic accuracy Additional Tests (held until after tpa decision) EKG CXR What is required before thrombolysis? Non-contrast CT or MRI POC Glucose PT/PTT/INR (only in patients on coumadin/heparin or suspected coagulopathy, POC testing) Gottesman RF, et al. Neurology 2006;67: Platelet Count (only if suspected thrombocytopenia) Cucchiara BL, et al. Stroke. 2007;38:

15 Evaluation - Neuroimaging Evolving standard of care Influenced by institutional capabilities Non-contrast CT CT/CTA CT/CTA/CTP MRI/MRA MRI/MRA/PWI Single or multiple tiers Role of Neuroimaging in Acute Ischemic Stroke 1. To differentiate from ischemic stroke mimics Hemorrhage, tumor, etc. 2. To confirm the diagnosis of ischemic stroke 3. To identify a large vessel occlusion that may require endovascular 4. To identify patients likely to benefit (or not benefit) from reperfusion therapies irrespective of treatment window

16 Non-contrast CT Standard in many/most institutions (<3-4.5 hrs) Fast, easy, lower cost Sensitive for intracranial hemorrhage Insensitive for acute ischemic stroke Not ideal for small or posterior fossa infarcts Early infarct signs Loss of grey-white differentiation Sulcal effacement Hyperdense vessel sign ASPECT score Clear hypodensity (<3 hrs) is rare reappraisal of onset time >1/3 MCA territory Neuroimaging

17 Neuroimaging CT angiography Useful to evaluate for a LVO amenable to thrombectomy Typically perfom both CTA neck and head to evaluate extracranial and intracranial vasculature May also help with assessment of collateral flow and tissue viability Apparent negligible risk of contrast-induced nephropathy in multiple single center series that incorporate CTA into acute stroke protocol

18 MRI Less availability, higher cost, patient contraindications (pacemaker), and increased scanner time? Diffusion-weighted imaging sequences have higher sensitivity and specificity for acute ischemic stroke Diffusion-FLAIR mismatch Neuroimaging

19 the effect of alteplase and to establish whether age or plan. The study protocol is available online. Lancet 2014; 384: NINDS A NINDS B ECASS I ECASS II ATLANTIS A ATLANTIS B ECASS III EPITHET IST-3 TOTAL Number randomised Summary of Benefits/Risks of IV rt-pa Treatment delay (hours) 2 0 (0 6) 2 0 (0 6) 4 4 (1 1) 4 3 (1 1) 4 3 (1 1) 4 4 (0 8) 4 0 (0 4) 4 9 (0 8) 4 2 (1 2) 4 0 (1 2) (>99%) 333 (100%) 87 (14%) 158 (20%) 22 (15%) 39 (6%) 620 (20%) 1549 (23%) > (<1%) 233 (38%) 265 (33%) 53 (37%) 249 (41%) 788 (96%) 31 (31%) 1148 (38%) 2768 (41%) > (48%) 370 (46%) 67 (47%) 321 (52%) 6 (1%) 69 (68%) 1266 (42%) 2394 (35%) Missing 5 (1%) 7 (1%) 4 (1%) 27 (3%) 1 (1%) 1 (<1%) 45 (1%) Age (years) 66 (11) 68 (12) 65 (12) 66 (11) 66 (13) 66 (11) 65 (12) 72 (13) 77 (12) 71 (13) (96%) 289 (87%) 615 (>99%) 792 (99%) 142 (100%) 608 (>99%) 805 (98%) 76 (75%) 1418 (47%) 5024 (74%) >80 12 (4%) 44 (13%) 5 (1%) 8 (1%) 3 (<1%) 15 (2%) 25 (25%) 1617 (53%) 1729 (26%) Missing 2 (<1%) 1 (<1%) 3 (<1%) Stroke severity (NIHSS) 14 (7) 15 (7) 12 (6) 12 (6) 13 (7) 11 (6) 10 (5) 13 (6) 12 (7) 12 (7) (5%) 13 (4%) 34 (5%) 47 (6%) 10 (7%) 47 (8%) 98 (12%) 1 (1%) 400 (13%) 666 (10%) (27%) 98 (29%) 189 (30%) 339 (42%) 57 (40%) 279 (46%) 389 (47%) 40 (40%) 1064 (35%) 2533 (37%) (23%) 63 (19%) 183 (30%) 232 (29%) 28 (20%) 128 (21%) 163 (20%) 22 (22%) 601 (20%) 1488 (22%) (26%) 78 (23%) 146 (24%) 113 (14%) 25 (18%) 106 (17%) 142 (17%) 29 (29%) 618 (20%) 1333 (20%) (15%) 74 (22%) 28 (5%) 43 (5%) 20 (14%) 33 (5%) 18 (2%) 9 (9%) 352 (12%) 622 (9%) Missing 8 (3%) 7 (2%) 40 (6%) 26 (3%) 2 (1%) 20 (3%) 11 (1%) * 114 (2%) Female 120 (41%) 142 (43%) 231 (37%) 331 (41%) 45 (32%) 250 (41%) 325 (40%) 43 (43%) 1570 (52%) 3057 (45%) History of hypertension 188 (65%) 220 (66%) 258 (42%) 412 (52%) 87 (61%) 364 (59%) 514 (63%) 71 (70%) 1954 (64%) 4068 (60%) History of stroke 49 (17%) 34 (10%) 83 (13%) 158 (20%) 31 (22%) 89 (15%) 89 (11%) 11 (11%) 699 (23%) 1243 (18%) History of diabetes mellitus 64 (22%) 67 (20%) 81 (13%) 169 (21%) 27 (19%) 130 (21%) 129 (16%) 23 (23%) 388 (13%) 1078 (16%) History of atrial fi brillation 55 (19%) 60 (18%) 113 (18%) 188 (24%) 37 (26%) 97 (16%) 108 (13%) 42 (42%) 914 (30%) 1614 (24%) Aspirin use 78 (27%) 93 (28%) 87 (14%) 196 (25%) 59 (42%) 211 (34%) 201 (24%) 30 (30%) 1306 (43%) 2261 (33%) Weight (kg) 78 (17) 78 (19) 74 (12) 75 (14) 80 (20) 79 (18) 78 (15) 75 (19) 72 (15) 75 (16) Systolic blood pressure (mmhg) 154 (21) 152 (21) 154 (23) 152 (21) 152 (24) 152 (21) 153 (21) 148 (19) 155 (24) 154 (22) Diastolic blood pressure (mmhg) 85 (13) 85 (14) 87 (13) 84 (13) 81 (14) 82 (14) 84 (14) 78 (13) 82 (15) 83 (14) Categorical data presented as n (%), continuous data presented as mean (SD). NINDS=National Institute of Neurological Disorders and Stroke; ECASS=European Cooperative Acute Stroke Study; ATLANTIS=Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke; EPITHET=Echoplanar Imaging Thrombolytic Evaluation Trial; IST=International Stroke Trial. *In IST-3, 244 patients had their baseline NIHSS score predicted from other measurements recorded at their baseline assessment. Ignoring these patients, the numbers of IST-3 patients in each category of baseline NIHSS score above would be 385, 972, 531, 559 and 344 respectively. Table 1: Baseline characteristics of patients in participating trials

20 Odds ratio (95% CI) Summary of Benefits/Risks of IV rt-pa 3 0 Interaction: 2 1=5 80 (p=0 016) Alteplase 80 (p=0 016) Alteplase Control Odds ratio 2 8 (95% CI)* (n=3391) (n=3391) (n=3365) Treatment delay 2 6 Treatment delay 3 0 h 259/787 (32 9%) 3 0 h 259/ (32 9%) 176/762 (23 1%) 1 75 > ( ) h 485/1375 (35 3%) outcome ood stroke > h 485/ (35 3%) >4 5 h 401/ (32 6%) Age (years) /2512 (39 4%) 1 6 >80 155/879 (17 6%) Baseline NIHSS score / (68 7%) 432/1437 (30 1%) 357/1166 (30 6%) 853/2515 (33 9%) 112/850 (13 2%) 189/321 (58 9%) 611/ (47 7%) 538/1252 (43 0%) 198/794 (24 9%) 175/808 (21 7%) /662 (11 6%) 55/671 (8 2%) 0 22/309 (7 1%) / (2 6%) Treatment delay (h) 1 26 >4 5 h( ) 401/1229 (32 6%) Age (years) 1 15 ( ) /2512 (39 4%) >80 155/879 (17 6%) Baseline 1 25 ( ) NIHSS score ( ) 237/345 (68 7%) Figure 1: Effect of timing of alteplase 0 5 treatment 0 75 on 1 good stroke 1 5 outcome (mrs 0 1) Alteplase worse Alteplase better The solid line is t between the log odds ratio for a good stroke Figure 2: Effect of alteplase on good stroke outcome (mrs 0 1), by treatment delay, age, and stroke severity *For each of the three baseline characteristics, estimates were derived from a single logistic regression model stratifi ed by trial, which enables separate estimation of the OR for each subgroup after adjustment for the other two baseline characteristics (but not for possible interactions with those characteristics). mrs=modifi ed Rankin Scale /1281 (47 7%) ( ) 198/794 (24 9%) /662 (11 6%) 1 22 ( ) 22 22/309 (7 1%) 1 24 ( ) 1 50 ( ) 3 25 ( ) Contr (n=33 176/7 432/1 357/1 853/2 112/8 189/3 538/1 175/8 55/6 8/3

21 Summary of Benefits/Risks of IV rt-pa Hemorrhagic Transformation HI-1 scattered, heterogeneous petechiae along the margins of the infarct (A) HI-2 more confluent but still heterogeneous petechiae within the infarcted area (B) PH-1 homogeneous hematoma covering <30% of the infarcted area and only mild space-occupying effect (C) PH-2 dense hematoma >30% of the lesion volume with significant spaceoccupying effect (D) Hemorrhagic transformation is the natural history of stroke (embolic strokes in particular) Only PH-2 are associated with neurologic deterioration

22 Test for varying log HRwith increasing duration of follow-up (p<0 0001) Summary of Benefits/Risks of IV rt-pa 0 Figure 5: Effect of alteplase on 90-day mortality by Patients can only contribute to a particular risk period *Estimated by Cox proportional hazards regression st Includes 91 versus 13 deaths caused by intracranial h type 2; figure 4) and 191 versus 191 deaths from oth Lancet Neur

23 Summary of Benefits/Risks of IV rt-pa Absolute risks and benefits an average absolute increase in disability-free survival (ie, mrs 0 1) at 3-6 months of about 10% for patients treated within 3.0 h about 5% for patients treated between 3.1 and 4.5 h

24 Summary of Benefits/Risks of IV rt-pa IV rt-pa <3 hours FDA approved AHA/ASA recommends treatment (level 1, grade A) IV rt-pa hours FDA no comment AHA/ASA recommends treatment (level 1, grade B)

25 The Code Stroke Streamlined process to collect information for urgent treatment decisions Code Stroke Team consisting of physicians, nurses, radiology techs, pharmacists, trainees, APPs, etc. Multiple simultaneous processes by various healthcare staff How fast?

26 The Code Stroke Helsinki University Central Hospital, Meilahti Hospital In % of ischemic stroke patients admitted to hospital treated with tpa median DNT 20 minutes 94% DNT <60 minutes Figure 1 Number of annually treated patients and median door-to-needle times Neurology 2012;79:

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28 Target Stroke American Heart Association initiative Goal of median DTN < 60 minutes Phase 2 - New Target: Stroke Honor Roll-Elite Plus: within 60 minutes in 75% or more AND median < 45 minutes

29 Code Stroke Process Prehospital Notification Page Code Stroke ETA 5 minutes Preregister ( John Doe ) Stroke Team meets EMS at the door and accompany to CT (CT in ED) Stopwatch on patient bed From EMS: Presenting symptoms, LKW and time of symptom discovery, baseline level of function, recent hospitalization/surgery, BP, medication (anticoagulant) list, POC glucose Vascular access NIHSS tpa kept in ED/CT Premix tpa for suspected candidates No written informed consent No waiting for coags/platelets unless indicated (POC testing available) tpa administered at CT Patient-specific feedback to EMS/ED personnel

30 Contraindications The AHA/ASA labeled contraindications for IV rt-pa historically reflected the exclusion list of the NINDS trial Exclusions in NINDS trial generally reflected 1. Potential stroke mimics (seizure, hyperglycemia, etc) 2. Patients for whom the hemorrhage risk was perceived to be elevated (recent stroke, prior ICH) At that time, very little was known about the risks and benefits! We use our current knowledge and judgment to determine risks/benefits in individual patients

31 through the same puncture site created by the transfer device in the stopper of the vial of reconstituted Activase. Peel the clear plastic hanger from the vial label. Hang the Activase vial from the resulting loop. Contraindications Activase is for intravenous administration only. Extravasation of Activase infusion can cause ecchymosis or inflammation. If extravasation occurs, terminate the infusion at that IV site and apply local therapy. Do not add any other medication to infusion solutions containing Activase. 3 The DOSAGE FDA FORMS revised/simplified AND STRENGTHS the package insert 50 mg lyophilized powder per single use vial with 50 ml SWFI USP for reconstitution recently to reflect evidence 100 mg lyophilized powder per single use vial with 100 ml SWFI USP for reconstitution 4 CONTRAINDICATIONS 4.1 Acute Ischemic Stroke Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit [see Warnings and Precautions (5.1)]: 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. 4.2 Acute Myocardial Infarction or Pulmonary Embolism Do not administer Activase for treatment of AMI or PE in the following situations in which the risk

32 Stroke 2013;44:

33 Purpose To critically review and evaluate the science behind individual eligibility criteria (indication/inclusion and contraindications/exclusion criteria) for intravenous recombinant tissue-type plasminogen activator (alteplase) treatment in acute ischemic stroke. This will allow us to better inform stroke providers of quantitative and qualitative risks associated with alteplase administration under selected commonly and uncommonly encountered clinical circumstances and to identify future research priorities concerning these eligibility criteria, which could potentially expand the safe and judicious use of alteplase and impro ve outcomes after stroke. Methods Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council s Scientific Statement Oversight AHA/ASA Scientific Statement Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons Bart M. Demaerschalk, MD, MSc, FRCPC, FAHA, Chair; Dawn O. Kleindorfer, MD, FAHA, Vice-Chair; Opeolu M. Adeoye, MD, MS, FAHA; Andrew M. Demchuk, MD; Jennifer E. Fugate, DO; James C. Grotta, MD; Alexander A. Khalessi, MD, MS, FAHA; Elad I. Levy, MD, MBA, FAHA; Yuko Y. Palesch, PhD; Shyam Prabhakaran, MD, MS, FAHA; Gustavo Saposnik, MD, MSc, FAHA; Jeffrey L. Saver, MD, FAHA; Eric E. Smith, MD, MPH, FAHA; on behalf of the American Heart Association Stroke Council and Council on Epidemiology and Prevention

34 Contraindications Mild Stroke Independent of NIHSS Non-disabling neurologic deficit Ex. Isolated sensory, isolated facial weakness, isolated dysarthria As opposed to disabling deficits Ex. Isolated moderate aphasia, isolated HH, motor score of >2 any limb

35 Contraindications For patients with mild but disabling stroke symptoms, intravenous alteplase is indicated within 3 hours from symptom onset of ischemic stroke. There should be no exclusion for patients with mild but nonetheless disabling stroke symptoms in the opinion of the treating physician from treatment with intravenous alteplase because there is proven clinical benefit for those patients (Class I; Level of Evidence A). Within 3 hours from symptom onset, treatment of patients with milder ischemic stroke symptoms that are judged as nondisabling may be considered. Treatment risks should be weighed against possible benefits; however, more study is needed to further define the risk-tobenefit ratio (Class IIb; Level of Evidence C). Stroke. 2016;47

36 Contraindications Rapidly Improving Ischemic Stroke Withhold treatment only if improvement is to a degree that remaining deficit is non-disabling Stroke. 2013;44

37 Contraindications Intravenous alteplase treatment is reasonable for patients who present with moderate to severe ischemic stroke and demonstrate early improvement but remain moderately impaired and potentially disabled in the judgment of the examiner (Class IIa; Level of Evidence A). Because time from onset of symptoms to treatment has such a powerful impact on outcome, delaying treatment with intravenous alteplase to monitor for further improvement is not recommended (Class III; Level of Evidence C). Stroke. 2016;47

38 Contraindications Hyperglycemia >400 mg/dl May mimic stroke Associated with poor outcome in tpa and non-tpa recipients May decrease recanalization/reperfusion and increase hemorrhagic transformation Consider co-administration of insulin If glucose lowered and deficits persist, treatment with IV tpa is reasonable

39 Contraindications Seizure Seizure may occur at onset of stroke Todd s paralysis or other post-ictal deficits may mimic stroke Does the patient have a history of epilepsy? Is there a history of similar episodes? Does imaging show a structural lesion in a location consistent with the current presentation? if evidence suggests that residual impairments are secondary to stroke and not a postictal phenomenon IV rt-pa is reasonable

40 Contraindications Perioperative/Recent Surgery or Procedure What is the current bleeding risk? Is the site compressible? What does the surgeon think? Recent CABG/craniotomy strict contraindication potential increased risk of surgical-site hemorrhage should be weighed against the anticipated benefits of reduced stroke-related neurological deficits

41 Contraindications Anticoagulation Warfarin INR>1.7; generally considered safe <1.7 SQ heparin/lmwh DVT prophylaxis dose unclear bleeding risk Heparin gtt elevated PTT Dabigatran unclear; elevated PTT (ecarin clotting time, thrombin time); treatment if no drug x 48 hours (normal renal function) OR normal coagulations studies Rivaroxaban, Apixaban or Edoxaban unclear; elevated PT (anti-fxa level); treatment if no drug x 48 hours (normal renal function) OR normal coagulations studies

42 Contraindications Conversion disorder I think Risk of hemorrhage is likely very low but not zero Neurology 2010;74:

43 Contraindications Stroke. 2013;44:00-00

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45 Summary of Benefits/Risks of Endovascular Recanalization Therapy Advances in technology higher rates of recanalization Efficiency in processes of care shorter onset to recanalization Refined patient selection/imaging differentiating candidates with potential benefit (small infarct core) from those without (large infarct core)

46 Summary of Benefits/Risks of Endovascular Recanalization Therapy Selection Confirmation of LVO Small to moderate infarct core

47 Summary of Benefits/Risks of Endovascular Recanalization Therapy Circulation. 2016;133:

48 NIHSS at 24 h Mean score 10 4 (8 7) 14 2 (7 8) ( ); p< ( ); p< Median score 8 (3 to 16) 15 (9 to 19) Summary of Benefits/Risks of Patients (%) Change in NIHSS score from baseline to 24 h Endovascular Recanalization Therapy d Rankin Mean Scale change at 90 days 6 4 (8 2) 2 6 (6 6) ( ); p< ( ); p< s in the intervention and control groups in the overall trial population (A) and for Median change 7 ( 12 to 1)* 2 ( 6 to 1) le for, intravenous alteplase (B). Distributions for other subgroups shown in Data in parentheses are SD or IQR, unless otherwise stated. NIHSS=National Institutes of Health Stroke Scale. *n=613. signifi cantly higher after Table 3: NIHSS score Intervention population Control population Risk difference (%) Rate ratio (95% CI) Odds ratio (95% CI) Intervention Control Risk Rate ratio Odds ratio mrs score reduction (shift population population difference (95% CI) 2 26* (95%( ); CI) analysis; primary (%) p< outcome)* Symptomatic 4 4% (28/634) 4 3% (28/653) ( ); 1 07 ( ); mrs score 0 1 at 90 days 26 9% 12 9% ( ); 2 49 ( ); intracranial p=0 82 p=0 81 (170/633) (83/645) p< p< haemorrhage mrs score 0 2 at 90 days 46 0% 26 5% ( ); 2 35 ( ); Parenchymal 5 1% (32/629) 5 3% (34/641) ( ); 0 99 ( ); (291/633) (171/645) p< p< haematoma type 2 p=0 97 p=0 97 NIHSS score 0 2 at 24 h 21 0% 8 3% ( ); 2 91 ( ); Mortality 15 3% (97/633) 18 9% (122/646) ( ); 0 77 ( ); (129/615) (52/630) p< p< p=0 15 p=0 16 Early neurological 50 2% 21 2% ( ); 4 04 ( ); Data recovery show the at 24 proportion h of patients (309/616) with outcome (134/633) (n/n), unless otherwise stated. p< p< Adjusted rate ratio (95% CI) Adjusted odds ratio (95% CI) Adjusted rate Adjusted odds ratio (95% CI) 2 49* ratio ( ); (95% CI) p< ( ); 2 06 ( ); p=0 81 p< ( ); 2 72 ( ); p=0 81 p< ( ); 2 71 ( ); 1 04 ( ); 1 04 ( ); p< p< p=0 88 p= ( ); 3 77 ( ); 0 82 ( ); 0 73 ( ); p< p< p=0 15 p= ( ); 4 36 ( ); p< p< Table Data show 4: Safety the proportion outcomes of at patients 90 days with outcome (n/n), unless otherwise stated. NIHSS=National Institutes of Health Stroke Scale. mrs=modifi ed Rankin Scale. *Common odds ratio indicating the odds of improvement of 1 point on the mrs. 24 Table h and 2: Efficacy showed outcomes more from improvement the pooled data between baseline and 24 h after treatment in patients assigned to thrombectomy (table 3). Mortality at 90 days and risk of parenchymal haematoma type 2 and symptomatic intracranial haemorrhage did not differ between populations (table 4). For subgroup analysis of mrs distribution shift at was noted for mortality (p interaction =0 33) but rate ratios were rarely signifi cant in any of the subgroups. Patients older than 80 years assigned to thrombectomy had a slightly reduced risk of death (41 [45%] of 91 patients died vs 30 [28%] of 107 assigned to control; adjusted rate ratio 0 60, 95% CI ; appendix p 3). Older age and higher baseline NIHSS score were

49 Summary of Benefits/Risks of Endovascular Recanalization Therapy n Age (years) (p interaction = 0 07) ASPECTS (p interaction = 0 29) Alteplase (p interaction = 0 43) Yes 1090 No 188 Stroke location (p interaction = 0 17) ICA M1 M2 NIHSS score (p interaction = 0 45) Onset to randomisation (p interaction = 0 10) 300 min 1070 >300 min 208 Sex (p interaction = 0 34) Male 676 Female 601 Tandem lesion (p interaction = 0 17) Yes No cor (95% CI) 1 36 ( ) 2 85 ( ) 2 58 ( ) 2 41 ( ) 2 44 ( ) 3 68 ( ) 1 24 ( ) 2 34 ( ) 2 66 ( ) 2 45 ( ) 2 43 ( ) 3 96 ( ) 2 29 ( ) 1 28 ( ) 1 67 ( ) 2 68 ( ) 2 81 ( ) 2 52 ( ) 2 66 ( ) 1 76 ( ) 2 54 ( ) 2 38 ( ) 2 95 ( ) 2 35 ( ) Total ( ) Favours control Favours intervention Figure 2: Forest plot showing adjusted treatment effect for mrs at 90 days in prespecified subgroups with

50 Downloaded from by guest on June 7, 2017 AHA/ASA Guideline 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Patients Endorsed should by the American receive Association endovascular of Neurological Surgeons therapy (AANS); Congress with a of Neurological stent retriever if they Surgeons meet (CNS); all the AANS/CNS following Cerebrovascular criteria Section; American (Class Society I; Level of Neuroradiology; of Evidence and A): Society of Vascular and Interventional Neurology (a) prestroke mrs score 0 to 1, William J. Powers, MD, FAHA, Chair; Colin P. Derdeyn, MD, FAHA, Vice Chair; (b) acute José ischemic Biller, MD, FAHA; stroke Christopher receiving S. Coffey, intravenous PhD; Brian L. Hoh, r-tpa MD, FAHA; within 4.5 hours Edward C. Jauch, MD, MS, FAHA; Karen C. Johnston, MD, MSc; of onset according to guidelines from professional medical societies, S. Claiborne Johnston, MD, PhD, FAHA; Alexander A. Khalessi, MD, MS, FAHA; (c) causative Chelsea occlusion S. Kidwell, of MD, the FAHA; internal James F. carotid Meschia, MD, artery FAHA; or proximal MCA Bruce Ovbiagele, MD, MSc, MAS, FAHA; Dileep R. Yavagal, MD, MBBS; (M1), on behalf of the American Heart Association Stroke Council (d) age 18 years, Purpose The aim of this guideline is to provide a focused update of the current recommendations for the endovascular (e) treatment NIHSS of acute score ischemic of stroke. 6, When there is overlap, the recommendations made here supersede those of previous guidelines. (f) Methods This ASPECTS focused of update 6, analyzes and results from 8 randomized, clinical trials of endovascular treatment and other relevant data published since It is not intended to be a complete literature review from the date of the previous (g) guideline treatment publication can but rather be to include initiated pivotal new (groin evidence puncture) that justifies changes within in current recommendations. 6 hours of Members of the writing committee were appointed by the American Heart Association/American Stroke Association symptom onset Stroke Council s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Recommendations follow the American Heart Association/ American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee.

51 Summary of Benefits/Risks of Endovascular Recanalization Therapy Treatment areas without consensus Beyond 6 hours* Vertebrobasilar occlusions* M2 occlusions With contraindications to IV rt-pa (recent stroke, head trauma, coagulopathy, etc.)* ASPECTS 3-5 Lower NIHSS Approach to tandem (proximal ICA stenosis/occlusion) General anesthesia versus conscious sedation Bypass CTA/multimodal imaging to save time Benefits of multimodal imaging to more accurately and reliably quantify infarct core and penumbra Prehospital bypass of ASRH and PSC for severe strokes

52 Summary Goal of acute stroke treatment is reperfusion of viable ischemic tissue Efficacy is highly time-dependent and benefits patients of all ages and stroke severities In hospital processes can streamline tpa decision-making Patients with moderate to severe stroke signs should be rapidly evaluated for large vessel occlusion and thrombectomy