The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7 th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7 th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention, 1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7 th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.Recommandations canadiennes pour les pratiques optimales de soins de l'AVC : prise en charge de l'AVC en phase aigue, 7e edition, mise a jour des lignes directrices de pratique 2022. La version mise a jour de 2022 de la section des Recommandations canadiennes# Introduction
Stroke prevention, treatment, and recovery have completely transformed over the past several decades due to research breakthroughs, increased awareness, and improvements to systems of care. Canada continues to be a world leader in driving innovation and change across the stroke continuum of care. In Canada, in 2017, there were 108,707 hospital visits for an acute stroke event, 2 and stroke remains a leading cause of adult disability with over 878,000 people living in Canada with the consequences of stroke. 3 In Canada, stroke systems of care have been growing since the late 1990s when acute thrombolysis became available. Currently, 232 hospitals (35%) are capable of providing acute thrombolysis, and this number now includes 155 hospitals with dedicated stroke teams and 95 acute stroke units. Twenty-five hospitals in Canada provide endovascular thrombectomy (EVT). 4 The global pandemic caused by the COVID-19 virus brought increased risk and worse outcomes for people with stroke and impacted response times by both the public and healthcare providers.  The 7 th update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management is a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, which have proven to reduce mortality and morbidity. The topics covered include those related to prehospital care, emergency department (ED) care, acute treatments with intravenous thrombolysis and EVT, the prevention and management in hospital complications, vascular risk factor reduction strategies, early rehabilitation, and end-of-life care. The theme of the 7 th edition of this CSBPR is building connections to optimize individual outcomes. Following an acute stroke, persons often present with multiple comorbid conditions, some of which may have contributed to their stroke, some that are the consequence of their stroke, and some which are unrelated. In many cases, comorbidities such as hypertension, carotid stenosis, and patent foramen ovale (PFO) may be first detected at the time of stroke. Regardless of the etiology, persons presenting with stroke and multiple comorbidities are more complex and are at risk of worse outcomes. These comorbid conditions must be considered within the treatment and care planning process to ensure effective and person-centered care.
The CSBPRs are intended to provide up-to-date evidence-based guidelines for the prevention and management of stroke and to promote optimal recovery and reintegration for people who have experienced stroke, including patients, families, and caregivers. The goal of disseminating and implementing these recommendations is to optimize evidence-based stroke care across Canada to reduce practice variations in care delivery and to narrow the gap between current knowledge and clinical practice. These recommendations have been developed in collaboration with the Canadian Stroke Consortium, Canada's national organization of stroke physicians. The recommendations are applicable to all healthcare providers, health system leaders and planners, and people living with stroke. The CSBPR Acute Stroke Management 2022, 7 th edition supersedes all recommendations contained in the 2018 CSBPR 6 th edition of Acute Stroke Management. 9 

# Guideline Development Methodology
The CSBPR development and update process follows a rigorous framework 10,11 and addresses all criteria defined within the Appraisal of Guidelines for Research and Evaluation II (AGREE II) Instrument components. 12 The methodology for development and updates to the CSBPR has been previously published, 13 and detailed methodology can be found on our Canadian Stroke Best Practices website at www.strokebestpractices.ca. An interdisciplinary group of experts was convened and participated in reviewing, drafting, and revising all recommendation statements. Eight people with lived experience of stroke (seven people with stroke and one caregiver) also actively participated in the review and update process as part of our acute stroke community consultation and review panel. 14 Searches were conducted by experienced personnel to identify peer-reviewed literature that examined each topic area addressed in the current module. Systematic reviews, meta-analyses, randomized controlled trials, and observational studies were included, as available. The literature for this module was current to September 2022. Following a standardized abstraction format, evidence tables were constructed including content from selected studies and provided to the writing group for review. The writing group discussed and debated the strength, importance, clinical relevance, and applicability of the evidence and, through consensus, developed a draft set of proposed recommendations. During this process, additional literature may have been identified and used to develop a final set of proposed recommendations. Evidence levels were assigned based on the quality of available evidence, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system.  Expert opinion was used to formulate recommendations in the absence of evidence. These guidelines have undergone extensive internal and external review, and consensus was achieved for all content. For additional details of the methodology and additional materials to support these recommendations, including rationales, system implications, performance measures, knowledge translation and implementation tools, evidence tables, and an extended summary of the evidence, please visit: www. strokebestpractices.ca. Supplemental online materials are available with this publication to support many of the recommendations included.

# Summary of Changes and Updates in the Acute Stroke Management Stroke, 7 th Edition, 2022
Significant updates and new additions to the CSBPR for Acute Stroke Management, 7 th edition 2022 are based, in part, on the results from several new, important clinical trials. Notable changes in the 7 th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy (DAPT) for stroke prevention, 1 the management of symptomatic intracerebral hemorrhage (ICH) following thrombolysis, acute stroke imaging (Section 4), pre-and post-op care of patients undergoing EVT (Section 5), medical assistance in dying (MAiD) (Section 11), and virtual stroke care in the ED and inpatient care (Sections 4 and 8).
An explicit effort was made to address sex and gender differences wherever possible. The first four sections of this guideline pertain to all people presenting with signs of acute stroke or TIA. The remaining sections pertain largely to the management of acute ischemic stroke and TIA. Guidelines for the management of patients with ICH were released in 2020, 18 while those for subarachnoid hemorrhage and cerebral venous thrombosis are in development.
Acute Stroke Management Recommendations, 7 th Edition, Update 2022
Note, please refer to online Supplemental Material accompanying these recommendations for additional definitions, information, inclusion criteria, and other implementation content. This manuscript has been translated into French and is also available as an online supplement.

# Section 1: Stroke Awareness, Recognition, and Response
Many members of the general public are unable to recognize the signs and symptoms of a stroke, or they attribute them to a less serious health issue.  While 61% of the population in Canada knows at least one sign of stroke, only 33% know at least two and only 10% know all three, based on the FAST (Face, Arms, Speech, Time) mnemonic. 22 The failure to recognize the signs of an acute stroke, either by the persons witnessing one or the person experiencing one, can delay contact with emergency services, which may in turn decrease a patient's opportunity to receive time-sensitive treatments. The number of public health campaigns designed to increase recognition of the signs and symptoms of stroke has increased over the past decade. One of the best recognized programs in the healthcare community is FAST. The results of a systematic review 23 suggest that stroke education using mass media campaigns can increase the likelihood of symptom recognition by 20% and increase the likelihood that persons would call emergency services by 19%. Mass media campaigns have also been shown to be associated with increases in the use of thrombolytic agents following acute stroke. 24 1. Stroke Awareness, Recognition, and Response Recommendations 2022 i. Organized and integrated stroke systems of care should be established and sustained in every health region in Canada to enable rapid emergency stroke management, including a public awareness campaign, public emergency system (such as 9-1-1), and monitoring systems that consider equity, age, sex, and gender diverse populations .
ii. All members of the public and all healthcare providers should be educated that stroke is a medical emergency  People experiencing signs of stroke require rapid assessment, diagnosis, and determination of risk for a recurrent stroke. Patients diagnosed to have TIA, or subacute, non-disabling ischemic strokes who are not candidates for hyperacute treatment with intravenous thrombolysis and/or EVT still require timely assessment and management, which can often be provided in an outpatient setting. The goal of outpatient management is to rapidly identify neurovascular risk factors, which may have precipitated the index event, and to initiate treatments to reduce the risk of recurrent events. The increased use and availability of sensitive neuroimaging to identify minor events as well as the increased use of antiplatelet agents, anticoagulants, antihypertensive agents, lipid-lowering agents, and carotid revascularization has been shown to significantly reduce the risk of major stroke after an initial minor event in recent years. In the TIARegistry.Org group study, 78.4% of patients were seen by a stroke specialist within 24 h of the event. 25 Most patients received key urgent investigations before discharge, and appropriate treatments were initiated. For example, 5.0% of patients received a new diagnosis of atrial fibrillation, of which 66.8% received anticoagulant therapy before discharge. Carotid stenosis of 50% was found in 15.5% of patients, of which 26.9% underwent carotid revascularization

# Triage and Initial Diagnostic Evaluation of Transient Ischemic Attack and Non-Disabling Stroke Recommendations 2022

# Notes
- Section 2 recommendations pertain to the initial management of patients with a suspected acute transient ischemic attack (TIA) or acute ischemic stroke who are not candidates for acute thrombolysis or endovascular intervention. For patients with suspected acute stroke that warrant hyperacute assessment to determine eligibility for intravenous thrombolysis and endovascular thrombectomy (EVT), refer to the current CSBPR Acute Stroke Management treatment recommendations, Sections 4 and 5.
- Refer to online Supplemental Materials for additional notes about this section. 1. Referral to a healthcare professional with stroke expertise should be considered for patients with a suspected uncommon cause of stroke, including for young patients with stroke (e.g., <45 years of age) 27 family history of young-onset stroke; suspected cerebral vasculitis or other intracranial arteriopathy/ vasculopathy; or suspected hereditary or acquired thrombophilia.
- Patients with symptoms of vertebrobasilar ischemia may present with fluctuating brainstem/cerebellar type symptoms (e.g., diplopia, dysarthria, dysphagia, non-positional vertigo, ataxia; rarely as isolated symptoms) over a longer time course (i.e., >48 hours) and can be mistaken for stroke mimics; however, these patients also require urgent assessment, neurovascular imaging, and management as these types of strokes can have a high morbidity. Consultation with a healthcare professional with stroke expertise is strongly encouraged.

# Setting:
In some regions, urgent/rapid TIA clinics are available that have rapid access to diagnostic services and specialist assessment and management. These clinics may be considered an appropriate referral option for patients with TIA and minor stroke. 
before discharge. The 1-year estimate of risk of the primary outcome, a composite of death from cardiovascular causes, nonfatal stroke, and nonfatal acute coronary syndrome, was 6.2% (95% confidence interval  5.5-7.0%). Estimates of stroke at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. These estimates were almost half of those compared with historical cohorts, possibly reflecting faster access to preventive care in the contemporary cohort. The availability of TIA outpatient clinics appears to be increasing. Based on the results of a geospatial analysis, there were 123 secondary prevention clinics in Canada, as of 2016. 26 While over 87% of the population had access to such a clinic within a 1-h drive, only 69.2% has access to a service that operates 5-7 days a week.

# Section 3: Emergency Medical Services
Emergency medical services (EMS) play a critical role in prehospital assessment and management of patients with suspected stroke. Patients arriving to hospital using EMS following a stroke experience fewer delays in receiving appropriate diagnostic tests, and are more likely to receive revascularization treatments, if eligible. In 2020, 69.0% of patients with stroke admitted to hospital in Canada were transported by EMS. 30 The odds of a patient receiving treatment with intravenous thrombolysis were increased by 52% if the patient was transported by EMS and increased by 75% if a system of hospital prenotification was employed. 31 Given the time-sensitive nature of acute stroke treatment, it is imperative that patients who may be candidates for these therapies be transported directly to comprehensive stroke centers as quickly as possible and whenever possible. The 90-day outcomes of patients who received EVT following direct transport have been shown to be better than those who were first transported to a primary stroke center. 32,33 However, in a recent cluster-randomized trial 34 in which paramedics transporting patients with ischemic stroke were randomized to the PASTA pathway (including structured prehospital information collection, prompted prenotification, and structured handover of information) or standard care, there was no significant difference between groups in the proportion of patients 
Virtual care-enabled evaluations of patients for secondary stroke prevention should be modeled on the topics defined in the post-stroke checklist and core elements of stroke prevention care. Refer to CSBPR Post Stroke Checklist for additional information at www.strokebestpractices.ca.
Validated approaches to virtual neurological exams should be followed.
- Processes should be in place to book follow-up tests, referrals, and other consultations after a virtual care visit.
- Processes to ensure appropriate documentation and communication to other team members who may be involved in remote care should be in place.
- Patients and their families should be encouraged to acquire home blood pressure monitors where appropriate and education or reliable resources on proper use should be provided. Mechanisms should be in place for follow-up and management of blood pressure for patients using home blood pressure devices, by either primary care providers or a stroke prevention service.
- For timely investigations, the use of prolonged cardiac monitors, if available, that can be sent to patient's homes, self-applied, and returned by mail, should be considered. ii. EMS communications centre: All regions in Canada should implement a dispatch process through their EMS communications centres to rapidly recognize signs or symptoms of stroke (e.g., FAST: Face, Arms, Speech, Time), prioritize response to the scene, and transport the patient to a hospital capable of providing acute services for rapid diagnosis and time-sensitive treatment of stroke (such as neuroimaging, and acute thrombolysis) .

# Emergency Medical
iii. After dispatching the ambulance, it is recommended that EMS communications centre personnel provide pre-arrival instructions to the person reporting the stroke (e.g., unlock door, move pets, determine stroke symptom onset time, determine current medications), in order to expedite, optimize, and improve safety for prehospital care . Note: If the person experiencing the signs of stroke is the one to contact EMS, they may not be able to comply with these requests.

# Paramedic On-Scene Management
Note: The on-scene goal is to recognize and mobilize. It is of the utmost importance to rapidly and safely transport suspected patients with stroke, as onscene management for patients with stroke is limited. After completing a brief screen tool to confirm signs and symptoms of a stroke, using an instrument such as FAST 35 or the Cincinnati Prehospital Stroke Scale, 36 EMS personnel should then conduct a subsequent screen to identify potential patients with large vessel occlusions (LVOs) in the anterior circulation who may be potential candidates for EVT. While several validated scales are currently available, most of which are derived from 3-6 components of the National Institutes of Health Stroke Scale (NIHSS), the sensitivities and specificities of these scales are not ideal 37 and most have not been externally validated in the field.

# Section 4: Emergency Department Evaluation
Standard assessments for patients with suspected acute stroke presenting to the ED include a rapid neurological examination and urgent brain and vascular imaging, followed by monitoring of vital signs, blood work, cardiovascular investigations, blood pressure management, glucose control, dysphagia screening, and seizure assessment. Given that some acute stroke symptoms including fatigue, anxiety, and dizziness may overlap with other cardiovascular and general medical conditions, 38 it is important to identify patients who are experiencing stroke "mimics" and to avoid unnecessary and expensive investigations and inappropriate long-term prevention treatments. Patients presenting with stroke symptoms may ultimately be diagnosed with other conditions such as migraine headache, vertigo, metabolic disturbances, brain tumors, or presyncope/syncope. 39 The NIHSS can be used to quickly screen for stroke-specific symptoms. For all patients arriving to hospital with suspected stroke or TIA, immediate brain and vascular imaging is the highest priority investigation once any life-threatening issues with respiration and circulation have been ruled out or addressed. A non-contrast CT scan is considered to be the imaging standard and the most cost-effective method to be used initially to identify acute ischemic stroke and to rule out intracranial hemorrhage. 40 While MRI with DWIs may be more sensitive in detecting early changes associated with ischemia, especially in patients with small infarcts, this technology may be not immediately available in many centers. 41 In the year 2019/20, there were 288 MRI machines in 378 facilities across Canada, equating to an availability of 10 units per million population. 42 Combined multimodal vascular imaging is ii. At hospital arrival, paramedics should provide the receiving hospital with verbal and written information related to the patient's stroke onset time, last known well time, presenting symptoms, and medications, to facilitate rapid assessment and decision-making . Refer to online Supplemental Materials Box 3A for more information.

# Section 3 Clinical Considerations
- The standard window for intravenous thrombolysis is 4.5 hours and the standard time window for EVT is 6 hours. However, patients may be considered eligible beyond these windows based on clinical factors and neuroimaging findings.
- Direct transport in many regions may take one of two potential pathways based on local or regional considerations:
a. Patients who may be eligible for intravenous thrombolysis may be directed to the closest centre, which may be a primary/advanced stroke centre or comprehensive stroke centre.
b. Patients who are likely candidates for EVT may be directed to (1) an EVT-enabled comprehensive stroke centre OR (2) a primary centre to rapidly receive intravenous thrombolysis and then be considered for transport to an EVT-enabled comprehensive stroke centre.
- On-scene time is an important variable that EMS professionals can control and needs to be monitored closely. Time lost due to inefficient on-scene care cannot be made up during subsequent transport to hospital, regardless of the use of lights and sirens.
- Patients should be transported by the method that allows the shortest transport time. In the event that a ground EMS response may cause significant delay in the patient transport, air transport should be considered where available.
- Pre-notification contact with the receiving emergency department should be initiated as soon as possible; where possible, the paramedics and receiving emergency department physician or stroke team member should communicate while enroute.
- For EVT-eligible patients, processes and or algorithms should be put in place that will easily enable a discussion to arrange for the patient to be transferred to the EVT-enabled comprehensive stroke centre in a timely manner. A three-way conference call among the referring clinician (paramedic or emergency department physician at a primary/advanced stroke centre), the receiving physician at the EVT-enabled centre, and the ambulance service involved in patient transport should support decision-making regarding direct to EVT centre or closer centre for initial imaging and assessment.

# Mobile Stroke Units:
The Canadian Stroke Best Practices writing group is currently unable to make a recommendation about mobile stroke units as published data on their use in the context of Canadian geography and health system organization are lacking. The group encourages further research into mobile stroke units in Canada as high-quality studies from other jurisdictions suggest that the use of these specialized units is associated with a reduced time to thrombolysis, an increased proportion of patients receiving thrombolysis, and better functional outcomes at 90 days.

# Initial Emergency Department Evaluation
i. All patients presenting to an emergency department with suspected acute stroke should be immediately assessed and undergo investigations without delay to establish a diagnosis and determine eligibility for thrombolysis and/or endovascular thrombectomy (  Note: Primary stroke centres should make all efforts to perform combined CT and CTA on patient arrival. The CT and CTA should be done at same time and not in separate visits to the imaging suite. Stroke centres that cannot do CTA should have pre-planned arrangements for rapid transfer of appropriate patients. They should complete non-contrast CT (NCCT) and offer intravenous thrombolysis as appropriate and then rapidly transfer the patient to a comprehensive stroke centre for more advanced imaging and consideration for EVT. (Refer to IV thrombolysis Section 5 for additional information).
ii. Note: If there are signs of hemorrhage on initial CT images there is no need to proceed to CTP imaging as part of initial imaging and CTA should be completed based on the clinical judgement of the treating physician.
Note: In most Canadian centres a CT approach may be more practical and more readily available than an MR approach. Choice of imaging modality should be based on most immediate availability and local resources.
Refer to Section 5 Acute Ischemic Stroke Treatment for information on administration of intravenous thrombolysis and EVT.
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- MRI as a first line for imaging can be challenging to obtain urgently in an emergency department setting. Obtaining an MRI scan should not delay decisionmaking regarding intravenous thrombolysis and EVT eligibility.
- Patients with a known allergy to contrast dye or with existing renal failure should not be excluded from consideration for EVT. 2. Routine checks of acute virtual stroke care equipment (both video-conferencing and imaging systems such as PACS) should be done to ensure the equipment will function properly in an emergency. This may be done as part of routine checks on other emergency equipment such as crash carts. Some systems may have a back-up system or alarms for malfunctioning equipment.
- Where electronic health records are available, health information sharing regulations that comply with provincial and federal privacy legislation should be developed, to allow an individual patient's record to be shared with referring and consulting facilities.
- Efforts should be made to design telestroke technology, so it is easy to use and operate, to facilitate adoption of the technology and decrease the time needed to meet educational requirements.
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extremely important, and in highly selected cases, perfusion scans with CT or MRI has the potential to identify patients with an ischemic penumbra and potentially viable brain tissue who may be appropriate for acute reperfusion therapies. Perfusion scans can be especially useful in selecting patient eligible for endovascular therapy in the 6-to-24-h window whereas in the 0-to-6-h time frame, and most cases can be selected with the use of CT and CTA alone.

# Section 5: Acute Ischemic Stroke Treatment
While the weight of evidence clearly indicates that treatment with intravenous alteplase, administered within 4.5 h of symptom onset, improves functional outcomes and reduces the risks of death or disability, 44,45 there are limited data on the benefit of treatment beyond this window. The most recent trials of thrombolytic therapy in the extended time window include EXTEND 46 and WAKE-UP, 47 in which patients presenting with symptoms beyond 4.5 h or with unknown time of onset were selected for treatment on the basis of advanced imaging. In both trials, patients receiving alteplase were more likely to achieve an excellent outcome (mRS 0-1) at 90 days, relative increase 44% 46 % and 61%, 47 symptomatic ICH and death were higher in the intervention group.
The results from several recent trials indicate that tenecteplase, a newer thrombolytic agent that has pharmacokinetic advantages over alteplase, is non-inferior to alteplase. Among the completed trials to date, the AcT trial 48 was the first to report that tenecteplase at a dose of 0.25 mg/kg (maximum 25 mg) is non-inferior to standard dose alteplase. At 90 days, 36.9% of patients in the tenecteplase group achieved the primary outcome (mRS score of 0-1) versus 34.8% in the alteplase group (unadjusted difference = 2.1%, 95% CI -2.6% to 6.9%; adjusted relative risk  = 11, 95% CI 10 to 12), meeting the non-inferiority threshold (the lower bound 95% CI of which was set at greater than -5%). There was no significant difference between groups in terms of mortality at 90 days (15.3% vs. 15.4%), or in the proportion with symptomatic ICH at 24 h (3.4% vs. 3.2%). In contrast to these findings, the NOR-TEST 2 49 trial of alteplase versus tenecteplase 0.4 mg/kg was halted early due to safety concerns, which included an increased risk of intracranial hemorrhage and mortality; however, the dose in the tenecteplase group was higher (0.4 mg/kg) than is currently recommended (0.25 mg/kg). In the EXTEND-IA TNK, 50 where patients with LVO received treatment with both thrombolysis and EVT, a significantly higher number of patients receiving tenecteplase 0.25 mg/kg achieved substantial reperfusion (22% vs. 10%, p = 0.02 for superiority), although the percentage of patients who were functionally independent at 90 days or who had achieved an excellent outcome did not differ between groups. Several clinical trials comparing tenecteplase with alteplase (ATTEST2 NCT0281440) and tenecteplase with placebo, or best medical management (TIMELESS NCT03785678, TWIST NCT0318 1360, and TEMPO-2 NCT02398656) are ongoing.
A 2021 Cochrane review 51 that included the results of 19 trials adds to the growing body of evidence indicating that EVT performed within 6 h of symptom onset is an extremely effective treatment for patients with LVO in the anterior circulation. Treatment with EVT was associated with a significantly higher likelihood of favorable outcome (RR = 1.61, 95% CI 1.42 to 1.82) with a high certainty of evidence, without a significantly increased risk of symptomatic intracranial hemorrhage (RR = 1.46, 95% CI 0.91 to 2.36) compared with usual care, which in many cases included the use of alteplase. For selected patients, the treatment window for EVT may be even longer. A pooled analysis of six randomized controlled trials 52 including patients who received treatment between 6 and 24 h after the onset of symptoms also found significantly better outcomes in patients in the intervention group. There was a significant shift in the ordinal analysis of mRS scores favoring less disability in the thrombectomy group (adjusted OR =254, 95% CI 183-354). The odds of achieving an mRS score of 0-1 or 0-2 at 90 days were both significantly higher in the EVT group (adjusted OR = 241, 95% CI 107-543 and adjusted OR = 388, 95% CI 194-778, respectively). The number needed to treat for one more patient to be independent with EVT was 2.6. Presence of a small to moderate ischemic core on non-contrast CT or MRI, usually consistent with an ASPECTS score of 6 for the anterior circulation.
a. Patients presenting with an intracranial artery occlusion and large core, such as those with an ASPECT score <6, may be considered for EVT based on expected risks and benefits, after consultation with a physician with stroke expertise and with the treating neurointerventionalist, along with the patient and/or family and/or substitute decision-makers.
4B.2 For posterior circulation: Imaging Criteria for Consideration of Endovascular Thrombectomy for Patients Arriving Within 6 Hours of Stroke Onset 1. Patients presenting with an intracranial occlusion of the posterior circulation (e.g., the basilar artery) may be considered for EVT based on expected risks and benefits, after consultation with a physician with stroke expertise and with the treating neurointerventionalist, along with the patient and family or substitute decision-maker.
Note: Randomized trials are ongoing, and this recommendation will be reviewed once the results become available.
Refer to online Supplemental Materials for additional information. iii. Alteplase dose: If using alteplase, the dose of 0.9 mg/kg to a maximum of 90 mg total dose should be administered, with 10% (0.09 mg/kg) given as an intravenous bolus over one minute and the remaining 90% Caution: The dosing of alteplase and tenecteplase for stroke is NOT the same as the dose protocols for administration of these medications for myocardial infarction or massive pulmonary embolism. a. The benefits and risks of providing intravenous thrombolysis to a patient who is being treated with the combination of antiplatelet and low-dose DOAC (i.e., COMPASS trial protocol) are unclear. Treatment may be considered in consultation with a stroke expert.
b. Anticoagulation is not a contraindication for EVT, and the decision to treat should be based on individual patient factors and assessment of benefit and risk.
c. Patients who present with stroke who are taking a DOAC may be considered for rapid reversal if otherwise eligible for IV thrombolysis and if a reversal agent is readily available. Consultation with an expert in stroke care in strongly advised for these cases.
- The use of epinephrine in angioedema or refractory hypotension should be reserved for life-threatening emergencies due to increased risk of hypertension post-medication administration.
- There are some situations where clinical trial data to support the use of intravenous thrombolytic therapy is more limited. In these situations, urgent consultation with a stroke expert is recommended along with the clinical judgment of the treating physician and discussion with the patient or substitute decision-makers.
a. For example, this may apply to pediatric patients with stroke (newborn to age 18 years); and pregnant women who experience an acute ischemic stroke. Refer to Canadian Stroke Best Practices Management of Acute Stroke During Pregnancy Consensus Statement for additional information. 53 5. (NEW FOR 2022) Evidence for the use of intravenous thrombolysis and EVT is derived from randomized trials that enrolled patients who were functionally independent at baseline. The use of intravenous thrombolysis and/or EVT in patients who are not functionally independent may be considered, based on careful review of risks and benefits for the patient. The patient's goals of care should be discussed in consultation with a physician with stroke expertise, and/or a neurointerventionalist, and the patient and/or family and/or substitute decision-makers.

# (NEW FOR 2022) Hypertension with symptomatic ICH:
In patients with symptomatic ICH who are hypertensive (>185/110 mm HG), blood pressure should be lowered, however, the specific target and duration of therapy are unknown at this time. Note: When an inpatient has a stroke while in hospital, all other sections of the CSBP modules apply to these patients for assessment, diagnosis, management, and recovery.

# Stroke While Already in Hospital
- "Admitted to hospital" is defined as any person admitted to an emergency department, inpatient unit, or outpatient clinic or rehabilitation service in a hospital setting.

# Endovascular Thrombectomy for Acute Ischemic Stroke
Refer to Section 4.2 and to online Supplemental Materials Boxes 4A, 4B, and 4C for detailed recommendations on neuroimaging-based selection criteria. 2. Device selection should be at the discretion of the interventionalists based on clinical and technical factors during the procedure.
- There should be a process at EVT centres to activate anesthesia without delay when deemed necessary.
- Patients with stroke discovered on awakening or with unknown last known well time should be considered for EVT if eligible based on imaging findings and clinical presentation. Refer to online Supplemental Materials Box 5C for more information.
- For patients undergoing EVT following administration of thrombolysis, there should not be a delay in proceeding to EVT to determine clinical effectiveness of thrombolysis.
- (NEW FOR 2022) When a patient who is eligible for both intravenous thrombolysis and EVT presents DIRECTLY TO AN EVT-CAPABLE HOSPITAL, a decision not to administer intravenous thrombolysis and proceed straight to EVT must balance both the patient-related and operational factors in play at that moment, for that patient. The overarching focus is to improve patient outcomes while safely reducing door-to-needle and door-to-puncture times. The main driver for an excellent outcome remains "time is brain".
Note: Clinical consideration 6 is controversial. It will be updated as additional evidence becomes available. In the meantime, clinicians involved in acute stroke care should focus on improving patient outcomes while safely reducing door-to-needle and door-to-puncture times. The main driver for excellent outcomes remains "time is brain".

# Seizure Management
i. Seizure in the presence of suspected acute stroke is not a contraindication for revascularization and could be treated using appropriate short-acting medications (e.g., lorazepam IV) if the seizures are not self-limited . While these criteria are designed to guide clinical decision-making, the decision to use thrombolysis should be based on the clinical judgment of the treating physician. The relative benefits of thrombolysis versus potential risks or contraindications should be weighed on an individual basis.

# Inclusion Criteria
Patients should be considered eligible for intravenous thrombolysis and/or EVT if they fulfill the following clinical criteria:
- Diagnosed with an acute ischemic stroke.
- The stroke is disabling (i.e., significantly impacting function), usually defined as National Institutes of Health Stroke Scale (NIHSS)>4.
- The risks and benefits of thrombolysis are within the patient's goals of care and take into consideration their functional status prior to stroke.
- Life expectancy of 3 months or more.
- Age 18 years. (Refer to pediatric guidelines for treatment <18 years of age).
 For adolescents, a decision to administer intravenous thrombolysis should be based on clinical judgment; presenting symptoms; patient age; and, if possible, consultation with a pediatric stroke specialist.
- Time from last known well (onset of stroke symptoms) is 4.5 hours refer to Section 5.1 for additional information.

# Absolute Exclusion Criteria
- Any source of active hemorrhage or any condition that could increase the risk of major hemorrhage after intravenous thrombolysis administration.
- Any hemorrhage on brain imaging.
Relative Exclusion Criteria (requiring clinical judgement based upon the specific situation. Consult Stroke Specialist at Comprehensive Stroke Centre if there are any questions or concerns about these criteria)

# Historical
- History of intracranial hemorrhage.
- Stroke or serious head or spinal trauma in the preceding 3 months.
- Major surgery (e.g., cardiac, thoracic, abdominal, or orthopedic) in the preceding 14 days. Risk varies according to the procedure.
- Arterial puncture at a non-compressible site in the previous 7 days.

# Clinical
- Stroke symptoms due to another non-ischemic acute neurological condition such as seizure with post-ictal Todd's paralysis or focal neurological signs due to severe hypo-or hyperglycemia.
- Hypertension refractory to aggressive hyperacute antihypertensive treatment such that target blood pressure <180/105 cannot be both achieved and maintained.
(Continued)

# Section 6: Acute Antiplatelet Therapy
Early antiplatelet therapy, provided soon after ischemic stroke, is known to improve outcomes. Acetylsalicylic acid (ASA) is the most commonly used agent. Results from two of the largest trials of ASA from several decades ago, the Chinese Acute Stroke Trial (CAST) 54 and the International Stroke Trial (IST) 55 represent the majority of the evidence base. In CAST, there were 5.4 fewer deaths and 4.7 fewer recurrent strokes per 1000 patients treated with daily aspirin of 160 mg after 4 weeks. In the aspirin arm of the factorial IST, patients with a suspected acute ischemic stroke received 300 mg/day of aspirin and a similar number avoided aspirin for 14 days. The risk of recurrent ischemic stroke was significantly lower in the aspirin arm, with a number needed to treat of 91, with no significant difference between groups in the frequency of symptomatic ICH. Short-term DAPT, for up to 21 days following ischemic stroke, with either clopidogrel or ticagrelor is more effective than ASA alone in reducing the risk of recurrent ischemic stroke in selected patients. In the POINT trial, Johnston et al. 56 estimated that for every 1,000 patients treated with 75 mg clopidogrel plus 81 mg aspirin for 90 days, 15 ischemic strokes would be prevented but 5 major hemorrhages would result. The greatest protection from treatment was seen in the first 21 days during which the risk of a major ischemic event was lowered by 35%. Although the antiplatelet regimen in the CHANCE trial 57 was slightly different than in the POINT trial, the results were similar, in that the risk of recurrent ischemic stroke was reduced by 33% in the DAPT group. 

# Acute Ischemic Stroke Treatment Recommendations 2022
- Currently prescribed and taking a direct non-vitamin K oral anticoagulant. Refer to Section 5.2 Clinical Considerations for additional information.

# CT or MRI Findings
- CT showing early signs of extensive infarction (e.g., >1/3 of middle cerebral artery  territory, or ASPECTS score <6).

# Laboratory
- Blood glucose concentration 22.2 mmol/L.
- Elevated activated partial-thromboplastin time.
- International Normalized Ratio >1.7.
- Platelet count <100,000 per cubic millimetre.

# Box 5C Inclusion Criteria for Endovascular Thrombectomy
Refer to Section 4.2 and Boxes 4B and 4C for detailed recommendations on neuroimaging-based selection criteria.
Patients should be considered eligible for endovascular thrombectomy if they fulfill the following clinical criteria:
- Diagnosed with an acute ischemic stroke.
- The stroke is disabling (i.e., significantly impacting function), usually defined as National Institutes of Health Stroke Scale (NIHSS)>4.
- There is a proven, clinically relevant (symptomatic), intra-or extracranial acute arterial occlusion that is amenable to endovascular intervention.
- The risks and benefits of endovascular thrombectomy are within the patient's goals of care and take into consideration their functional status prior to stroke.
- Age 18 years. (Refer to pediatric guidelines for treatment <18 years of age).
a. Currently, there is no evidence for EVT in pediatric populations and the decision to treat should be based on the potential benefits and risks of the therapy, made by a physician with pediatric stroke expertise in consultation with the EVT provider and the patient and/or family or substitute decision-makers.
- Intravenous thrombolysis: If intravenous thrombolysis is given in conjunction with endovascular thrombectomy, refer to Box 5B for additional inclusion criteria. 8. Imaging: Patients must qualify for imaging criteria in early and late windows as described in Boxes 4B and 4C.
- Time to treatment: The decision to proceed with EVT should be shared by the physician with clinical stroke expertise and the neuro-interventionalist, who will use the available imaging information as is indicated.
a. Specifically:
i. Patients should have immediate neurovascular imaging (see above) to determine eligibility. Patients can be considered for imaging within a 24-hour window from stroke symptom onset or last known well. ii. For patients presenting <6 hours from stroke symptom onset or last known well to initiation of treatment (i.e., arterial puncture), all patients who meet eligibility criteria should be treated. iii. For patients presenting between 6 and 24 hours from last known well, selected patients may be treated if they meet clinical and imaging criteria and based on local protocols and available expertise in EVT. Patients who are at a very high risk for TIA or minor ischemic stroke caused by high-grade carotid stenosis who are candidates for urgent carotid endarterectomy or carotid stenting should be reviewed with the surgeon or interventionalist to determine the appropriate timing and selection of antiplatelet agent(s).
- For patients on dual antiplatelet therapy, gastrointestinal protection may be considered for those at higher risk of gastrointestinal bleeding.
- For patients with acute stroke or TIA and non-valvular atrial fibrillation, anticoagulation should be initiated; however, there is a lack of randomized evidence to guide specific timing. According to expert consensus, a general approach to the target timing of initiation of DOAC therapy post-stroke is as follows:
a. For patients with a brief TIA and no visible infarct or hemorrhage on imaging, anticoagulation may be started within the first 24 hours post-TIA.
b. For patients with a minor clinical stroke/small non-hemorrhagic infarct on imaging, anticoagulation may be started 3 days post-stroke.
(Continued)
In the THALES trial, 1 patients with minor acute ischemic stroke treated with 90 mg ticagrelor twice a day  75-100 aspirin mg/ day also experienced fewer recurrent strokes and death within 30 days (5.5% vs. 6.6%, HR = 0.83, 95% CI 0.71-0.96, number needed to treat =92), compared with patients treated with aspirin alone. 1 However, these benefits were accompanied by a 3.5 to 4 times increased risk of severe or fatal bleeding and intracranial hemorrhage.

# Section 7: Hemicraniectomy
Due to higher risks of cerebral edema, increased intracranial pressure, and subsequent cerebral herniation, mortality is higher for patients with malignant MCA stroke. For these patients, decompressive hemicraniectomy may be a surgical option. In persons under the age of 60 years, early decompressive hemicraniectomy increases the odds of a reasonable functional outcome (mRS score of 0-3) at 1 year.  The data are limited for patients over the age of 60 years. In the DESTINY 2 trial, 61 82 patients with a median age of 70 years were randomized to hemicraniectomy or standard care: a significantly higher proportion of patients in the surgical group were alive and living without severe disability (mRS score of 0-4) at 6 months (38% vs.18%, OR = 2.91, 95% CI 1.06-7.49) compared with patients in the medical management group. However, no patients in either the surgical or medical care groups had overall good outcomes (mRS score of 0-2) at 6 or 12 months and most of the survivors required assistance with most bodily needs. In a recent systematic review, which included the results from seven trials, including DESTINY 2, as well as six trials of patients aged <60 years (DESTINY, 59 DESTINY II, 61 DECIMAL, 60 and HAMLET), 62 the odds of a favorable outcome (mRS 0-3) at 1 year were significantly higher in the surgical group (adjusted OR = 2.95, 95% CI 1.55-5.60) and the odds of death at 1 year were significantly lower (adjusted OR = 0.16; 95% CI 0.10-0.24).
(Continued )
- Acute Antithrombotic Therapy Recommendations 2022 c. For patients with a moderate clinical stroke/moderate-sized infarct on imaging (without hemorrhage on CT), anticoagulation may be started 6 to 7 days post-stroke.
d. For patients with a severe clinical stroke/large-sized infarct on imaging (without hemorrhage on CT), anticoagulation may be started 12 to 14 days post-stroke.
e. Antiplatelet therapy may be used prior to initiating anticoagulation.
Refer to CSBPR Secondary Prevention of Stroke module Sections 6 and 7 for additional information on management of atrial fibrillation and choice of therapeutic agents. 13 4. For patients who experience a stroke while receiving one antiplatelet agent, stroke etiology should be reassessed and addressed, and all other vascular risk factors aggressively managed. Continuing the current antiplatelet agent or switching to a different agent are reasonable options. At the time of writing, evidence is lacking to make more specific recommendations. i. For patients aged 18 -60 years old, hemicraniectomy should be considered as a life-saving measure for patients in the early stages of extensive (malignant) middle cerebral artery (MCA) territory ischemic stroke (defined as infarction size >50% MCA territory on visual inspection, or an ischemic lesion volume >150 cm 3 and concomitant clinical features) if patients or their substitute decision-makers are willing to accept a significant risk of living with a degree of disability that may leave them dependent on others for their activities of daily living.  Patients who are admitted to stroke units are more likely to survive, return home, and regain their independence compared to patients who are admitted to non-specialized units. The most recent update of the Stroke Unit Trialists' Collaboration 63 identified 29 randomized and quasi-randomized trials, including 5,902 participants, comparing stroke unit care with alternative, less organized care (e.g., an acute medical ward). Compared to less organized forms of care, stroke unit care was associated with a significant reduction in the odds of death (OR = 0.76, 95% CI 0.66 to 0.88), a poor outcome (OR = 0.77, 95% CI 0.69 to 0.87), and death or dependency (OR = 0.75, 95% CI 0.66 to 0.85) at a median follow-up of 1 year. These results were based on moderate quality evidence. Stroke unit care was superior regardless of age, sex, initial stroke severity, stroke type, trial quality, and duration of follow-up.
In Canada, access to stroke unit care varies by region. A survey conducted in 2013/14 identified 32 stroke units within the province of Ontario, of which 21 were acute stroke units, 10 were integrated stroke units, and 1 which was classified as a rehabilitation stroke unit. 64 The estimated average number of stroke patients served per stroke unit was 604 with large variation across centers. iii. Patients with suspected elevation in intracranial pressure may be managed according to institutional protocols (e.g., administration of hyperosmolar therapy, head of bed elevation) .
Section 7 Clinical Considerations:
- Global disability and quality of life outcomes are similar regardless of whether the hemicraniectomy was for right or left sided MCA infarction. 2. Whereas age alone is not a reason to forego hemicraniectomy, the DESTINY II trail reported that for 0% of patients over 60 years had mild or no disability (mRS of 0 -2), and only 7% could function independently (mRS 0-3) after hemicraniectomy surgery.

# Section 9: Inpatient Prevention and Management of Complications Following Stroke 2022
Medical complications are relatively common following stroke and may negatively impact the recovery process, with the potential to result in poorer outcomes. 65 Estimates of the percentage of patients who experience at least one medical complication during hospitalization vary widely from 25% 66 to 85%. 67 Some of the most commonly cited complications include urinary tract infections, fever, pneumonia, and deep vein thrombosis (DVT). Examples of measures that can be taken to reduce the risks of these complications include pharmacological venous thromboembolism prophylaxis, 68 and the use of thigh-high intermittent pneumatic compression (IPC) devices, 69 to prevent thromboembolism, dysphagia screening to reduce the risk of pneumonia, 70 and the avoidance of the use of indwelling catheters to prevent urinary tract infections. 71 Early mobilization post-stroke can reduce the length of hospitalization and is associated with greater ability to perform activities of daily living at 3 months. 72 Cardiac investigations should also be conducted to identify previously undetected or paroxysmal atrial fibrillation, or other cardiac abnormalities. 73,74 (Continued ) Advance care planning (ACP) is a process of reflection and communication in which individuals reflect on their wishes and values to make decisions regarding their healthcare in consultation with healthcare providers, should they become incapable of participating in decision-making at a later date. 76 While there is evidence supporting ACP in the primary care setting, there are limited data on ACP in acute care in general, and even less following stroke. Green et al. 77 used participant observation and semi-structured interviews to gather information related to the communication process regarding ACP from 14 patients, recruited from an acute stroke unit and 2 rehabilitation units, and 4 HCPs. Four key themes emerged as to why or why not participants engaged in the ACP process. First, there was a perceived lack of urgency by participants, many of whom felt the physician and/or family members would make decisions in accordance with their wishes; second, there was a lack of initiation by HCPs to discuss issues around ACP; third, HCPs expressed hesitation about initiating discussions related to ACP, and uncertainty as the best timing for such discussions. Fourth, there was also a lack of understanding of ACP, especially as compared to advance directives, designation of care, and living wills. Although no stroke-specific studies have been published that examine the effectiveness of ACP, several studies included patients with stroke. Results from a small number of studies suggest that interventions aimed at increasing ACP have been successful in significantly increasing the likelihood that end-of-life wishes are known and respected. 78,79 (Continued )  Palliative care is an approach that aims to reduce suffering and improve the quality of life for people who are living with life-limiting illness through the provision of pain and symptom management, psychological, social, emotional, spiritual, and practical support, and support for caregivers during the illness and after the death of the person they are caring for. 80 Palliative care provides comprehensive care throughout a person's illness trajectory and is not solely limited to end-of-life care. The role of palliative care may be complicated as prognosis in the earliest phase of stroke can be unclear. 81 There is currently no integrated model of palliative care in stroke care addressing the appropriate moment to initiate palliative care discussions 82 or which healthcare provider(s) should raise the topic; however, there is agreement that the approach should be interdisciplinary and patient-and familycentered. The palliative care needs of patients following stroke are typically related to the management of common symptoms such as dyspnea, pain, and xerostomia. 83 While palliative care pathways have been developed to ensure that patients receive the most appropriate care possible in the last days of life, there is an absence of high-quality evidence to suggest that current pathways are effective, highlighting the need for additional research in this area. 84 In terms of specific interventions designed to address many common palliative care issues, a systematic review by Cowey et al. 85 concluded that there was insufficient evidence to recommend the best and most effective approaches to this important and essential component of care. iii. Advance care planning may include identifying a substitute decision-maker (proxy, agent, or power of attorney), and discussing the patient's personal values and preferences to be applied in future if the need arises to make healthcare decisions or provide consent on behalf of the patient Challenges and Future Directions
The 7 th update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management provides a detailed series of recommendations applicable to the care of all adults in Canada who have sustained an ischemic stroke or TIA. These guidelines have been developed through a rigorous process; efforts must now turn to their rapid implementation, especially of the new recommendations, based on emerging high-quality evidence, so as to increase equitable access to timely acute stroke care for all people in Canada. This edition of the guidelines has incorporated Tenecteplase 0.25 mg/kg as an alternate thrombolytic for acute ischemic stroke based on the landmark Canadian AcT trial. It is expected that the knowledge of the clinical applications of tenecteplase will continue to advance, particularly as it pertains to its use in the setting of patients with intracranial arterial occlusions who may or may not be candidates for thrombectomy.
Thrombectomy with or without thrombolysis is the topic of several recent randomized trials; this issue will likely be settled by the time the next edition of these guidelines is ready for publication. At present, trials that most closely reflect Canadian practice suggest that thrombolysis should NOT be withheld for patients who are also candidates for thrombectomy; all eligible patients should receive thrombolysis, regardless of whether they also may receive thrombectomy. We acknowledge the possibility that further refinement in the understanding of the risks and benefits of combination therapy could alter these recommendations. Specifically, it is anticipated that further experience with tenecteplase may impact this calculus in important ways.
We are also excited about the prospect of further developments in the evidence to support EVT for patients with acute ischemic stroke of the posterior circulation. These patients were excluded from the landmark thrombectomy trials published between 2014 and 2018, and upon which current recommendations are based. With the advent of data from high-quality randomized trials, we expect to be able to provide more specific recommendations about thrombectomy for patients suffering strokes of the posterior circulation in the next edition of these guidelines.
The field of neuroprotection is also likely to advance in the coming years. The ESCAPE NA-1 trial suggested that nerinetide could be an effective neuroprotectant in patients with acute ischemic stroke not receiving thrombolysis, and that hypothesis is currently being tested in the Canadian-led ESCAPE NEXT trial. If that trial should be successful, it will be the first instance in the history of clinical neuroscience that a neuroprotectant agent has been found to be clinically effective in humans. Such a discovery could have significant ramifications for the management of acute ischemic stroke and may also influence the care of patients with ICH, subarachnoid hemorrhage, traumatic brain injury, and cardiac arrest.