2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association

Abstract

HomeStrokeVol. 52, No. 72021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toSupplementary MaterialsFree AccessReview ArticlePDF/EPUB2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association Dawn O. Kleindorfer, MD, FAHA, Chair Amytis Towfighi, MD, FAHA, Vice Chair Seemant Chaturvedi, MD, FAHA Kevin M. Cockroft, MD, MSc, FAHA Jose Gutierrez, MD, MPH Debbie Lombardi-Hill, BS, FAHA Hooman Kamel, MD Walter N. Kernan, MD Steven J. Kittner, MD, MPH, FAHA Enrique C. Leira, MD, MS, FAHA Olive Lennon, PhD James F. Meschia, MD, FAHA Thanh N. Nguyen, MD, FAHA Peter M. Pollak, MD Pasquale Santangeli, MD, PhD Anjail Z. Sharrief, MD, MPH, FAHA Sidney C. Smith Jr, MD, FAHA Tanya N. Turan, MD, MS, FAHA Linda S. WilliamsMD, FAHA Dawn O. KleindorferDawn O. Kleindorfer , Amytis TowfighiAmytis Towfighi , Seemant ChaturvediSeemant Chaturvedi , Kevin M. CockroftKevin M. Cockroft , Jose GutierrezJose Gutierrez , Debbie Lombardi-HillDebbie Lombardi-Hill , Hooman KamelHooman Kamel , Walter N. KernanWalter N. Kernan , Steven J. KittnerSteven J. Kittner , Enrique C. LeiraEnrique C. Leira , Olive LennonOlive Lennon , James F. MeschiaJames F. Meschia , Thanh N. NguyenThanh N. Nguyen , Peter M. PollakPeter M. Pollak , Pasquale SantangeliPasquale Santangeli , Anjail Z. SharriefAnjail Z. Sharrief , Sidney C. Smith JrSidney C. Smith Jr , Tanya N. TuranTanya N. Turan , and Linda S. WilliamsLinda S. Williams Originally published24 May 2021https://doi.org/10.1161/STR.0000000000000375Stroke. 2021;52:e364–e467is corrected byCorrection to: 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke AssociationTOP 10 Take-Home Messages for the Secondary Stroke Prevention GuidelineSpecific recommendations for prevention strategies often depend on the ischemic stroke/transient ischemic attack subtype. Therefore, new in this guideline is a section describing recommendations for the diagnostic workup after ischemic stroke, to define ischemic stroke etiology (when possible), and to identify targets for treatment in order to reduce the risk of recurrent ischemic stroke. Recommendations are now grouped by etiologic subtype.Management of vascular risk factors remains extremely important in secondary stroke prevention, including (but not limited to) diabetes, smoking cessation, lipids, and especially hypertension. Intensive medical management, often performed by multidisciplinary teams, is usually best, with goals of therapy tailored to the individual patient.Lifestyle factors, including healthy diet and physical activity, are important for preventing a second stroke. Low-salt and Mediterranean diets are recommended for stroke risk reduction. Patients with stroke are especially at risk for sedentary and prolonged sitting behaviors, and they should be encouraged to perform physical activity in a supervised and safe manner.Changing patient behaviors such as diet, exercise, and medication compliance requires more than just simple advice or a brochure from their physician. Programs that use theoretical models of behavior change, proven techniques, and multidisciplinary support are needed.Antithrombotic therapy, including antiplatelet or anticoagulant agents, is recommended for nearly all patients without contraindications. With very few exceptions, the combination of antiplatelets and anticoagulation is typically not indicated for secondary stroke prevention. Dual antiplatelet therapy is not recommended long term, and short term, dual antiplatelet therapy is recommended only in very specific patients, including those with early arriving minor stroke and high-risk transient ischemic attack or severe symptomatic intracranial stenosis.Atrial fibrillation remains a common and high-risk condition for second ischemic stroke. Anticoagulation is usually recommended if the patient has no contraindications. Heart rhythm monitoring for occult atrial fibrillation is usually recommended if no other cause of stroke is discovered.Extracranial carotid artery disease is an important and treatable cause of stroke. Patients with severe stenosis ipsilateral to a nondisabling stroke or transient ischemic attack who are candidates for intervention should have the stenosis fixed, likely relatively early after their ischemic stroke. The choice between carotid endarterectomy and carotid artery stenting should be driven by specific patient comorbidities and features of their vascular anatomy.Patients with severe intracranial stenosis in the vascular territory of ischemic stroke or transient ischemic attack should not receive angioplasty and stenting as a first-line therapy for preventing recurrence. Aggressive medical management of risk factors and short-term dual antiplatelet therapy are preferred.There have been several studies evaluating secondary stroke prevention of patent foramen ovale closure since the previous guideline in 2014. It is now considered reasonable to percutaneously close patent foramen ovale in patients who meet each of the following criteria: age 18–60 years, nonlacunar stroke, no other identified cause, and high risk patent foramen ovale features.Patients with embolic stroke of uncertain source should not be treated empirically with anticoagulants or ticagrelor because it was found to be of no benefit.PreambleSince 1990, the American Heart Association (AHA)/American Stroke Association (ASA)* have translated scientific evidence into clinical practice guidelines with recommendations to improve cerebrovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a foundation for the delivery of quality cerebrovascular care. The AHA/ASA sponsor the development and publication of clinical practice guidelines without commercial support, and members volunteer their time to the writing and review efforts.Clinical practice guidelines for stroke provide recommendations applicable to patients with or at risk of developing cerebrovascular disease. The focus is on medical practice in the United States, but many aspects are relevant to patients throughout the world. Although it must be acknowledged that guidelines may be used to inform regulatory or payer decisions, the core intent is to improve quality of care and to align with patients’ interests. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment; furthermore, the recommendations set forth should be considered in the context of individual patient values, preferences, and associated conditions.The AHA/ASA strive to ensure that guideline writing groups contain requisite expertise and are representative of the broader medical community by selecting experts from a broad array of backgrounds, representing different sexes, races, ethnicities, intellectual perspectives, geographic regions, and scopes of clinical practice and by inviting organizations and professional societies with related interests and expertise to participate as endorsers. The AHA/ASA have rigorous policies and methods for development of guidelines that limit bias and prevent improper influence. The complete policy on relationships with industry and other entities can be found at https://professional.heart.org/-/media/phd-files/guidelines-and-statements/policies-devolopment/aha-asa-disclosure-rwi-policy-5118.pdf?la=en.Beginning in 2017, numerous modifications to the guidelines have been implemented to make guidelines shorter and to enhance “user friendliness.” Guidelines are written and presented in a modular knowledge chunk format, in which each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text, and, when appropriate, flow diagrams or additional tables. Hyperlinked references are provided for each modular knowledge chunk to facilitate quick access and review. Other modifications to the guidelines include the addition of Knowledge Gaps and Future Research segments in some sections and a web guideline supplement (Data Supplement) for useful but noncritical tables and figures.Sepideh Amin-Hanjani, MD, FAHAImmediate Past Chair, AHA Stroke Council Scientific Statement Oversight CommitteeJoseph P. Broderick, MD, FAHAChair, AHA Stroke Council Scientific Statement Oversight Committee1. INTRODUCTIONEach year, ≈795 000 individuals in the United States experience a stroke, of which 87% (690 000) are ischemic and 185 000 are recurrent.1 Approximately 240 000 individuals experience a transient ischemic attack (TIA) each year.2 The risk of recurrent stroke or TIA is high but can be mitigated with appropriate secondary stroke prevention. In fact, cohort studies have shown a reduction in recurrent stroke and TIA rates in recent years as secondary stroke prevention strategies have improved.3,4 A meta-analysis of randomized controlled trials (RCTs) of secondary stroke prevention therapies published from 1960 to 2009 showed a reduction in annual stroke recurrence from 8.7% in the 1960s to 5.0% in the 2000s, with the reduction driven largely by improved blood pressure (BP) control and use of antiplatelet therapy.5 The changes may have been influenced by changes in diagnostic criteria and differing sensitivities of diagnostic tests over the years.The overwhelming majority of strokes can be prevented through BP control, a healthy diet, regular physical activity, and smoking cessation. In fact, 5 factors—BP, diet, physical inactivity, smoking, and abdominal obesity—accounted for 82% and 90% of the population-attributable risk (PAR) for ischemic and hemorrhagic stroke in the INTERSTROKE study (Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries).5a Similarly, the Global Burden of Disease Study showed that 90.5% (95% uncertainty interval, 88.5–92.2) of the global burden of stroke was attributable to modifiable risk factors.6 A modeling study showed that targeting multiple risk factors has additive benefits for secondary prevention; specifically, aspirin, statin, and antihypertensive medications, combined with diet modification and exercise, can result in an 80% cumulative risk reduction in recurrent vascular events.7 Although the benefits of a healthy lifestyle and vascular risk factor control are well documented,8,9 risk factors remain poorly controlled among stroke survivors.10–141.1. Methodology and Evidence ReviewThis guideline provides a comprehensive yet succinct compilation of practical guidance for the secondary prevention of ischemic stroke or TIA (ie, prevention of ischemic stroke or TIA in individuals with a history of stroke or TIA). We aim to promote optimal dissemination of information by using concise language and formatting. The recommendations listed in this guideline are, whenever possible, evidence based and supported by an extensive evidence review. A search for literature derived from research involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline was conducted between July 2019 and February 2020. Additional trials published between February and June 2020 that affected the guideline recommendations were also included. For specific search terms used, please see the Data Supplement, which also contains the final evidence tables that summarize the evidence used by the guideline writing group to formulate recommendations. References selected and published in the present document are representative and not all inclusive.An independent Evidence Review Committee was commissioned to perform a formal systematic review of a critical clinical question (Table 1) related to secondary stroke prevention, the results of which were considered by the writing group for incorporation into the present guideline. Concurrently with this process, writing group members evaluated study data relevant to the rest of the guideline. The results of these evidence reviews were evaluated by the writing group for incorporation into the present guideline.Table 1. Evidence Review Committee QuestionQuestion No.QuestionSection No.1In patients with an ischemic stroke or TIA, what are the benefits and risks of DAPT compared to single antiplatelet therapy within 5 y for prevention of recurrent stroke?5.19DAPT indicates dual antiplatelet therapy; and TIA, transient ischemic attack.Each topic area was assigned a primary author and a primary, and sometimes secondary, reviewer. Author assignments were based on the areas of expertise of the members of the writing group members and their lack of any relationships with industry related to the section material. All recommendations were fully reviewed and discussed among the full committee to allow diverse perspectives and considerations for this guideline. Recommendations were then voted on to reach consensus. The systematic review has been published in conjunction with this guideline and includes its respective data supplements.151.2. Organization of the Writing GroupThe writing group consisted of neurologists, neurological surgeons, cardiologists, internists, and a lay/patient representative. The writing group included representatives from the AHA/ASA and the American Academy of Neurology. Appendix 1 lists writing group members’ relevant relationships with industry and other entities. For the purposes of full transparency, the writing group members’ comprehensive disclosure information is available online.1.3. Document Review and ApprovalThis document was reviewed by the AHA’s Stroke Council Scientific Statement Oversight Committee; the AHA’s Science Advisory and Coordinating Committee; the AHA’s Executive Committee; reviewers from the American Academy of Neurology, from the Society of Vascular and Interventional Neurology, and from the American Association of Neurological Surgeons and Congress of Neurological Surgeons; as well as by 55 individual content reviewers. The individual reviewers’ relationships with industry information is available in Appendix 2.This document was approved for publication by the governing bodies of the ASA and the AHA. It was reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, was endorsed by the Society of Vascular and Interventional Neurology, and the American Academy of Neurology affirmed the value of the guideline.1.4. Scope of the GuidelineThe aim of the present guideline is to provide clinicians with evidence-based recommendations for the prevention of future stroke among survivors of ischemic stroke or TIA. It should be noted that this guideline does not cover the following topics, which have been addressed elsewhere:Acute management decisions (covered in the “2019 Update to the 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke”16),Intracerebral hemorrhage (ICH; covered in the “Guidelines for the Management of Spontaneous Intracerebral Hemorrhage”17),Primary prevention (covered in the “Guidelines for the Primary Prevention of Stroke”18 and “2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease”19),Special considerations for stroke prevention in women (covered in the “Guidelines for the Prevention of Stroke in Women”20), andCerebral venous sinus thrombosis (covered in “Diagnosis and Management of Cerebral Venous Thrombosis”22).In general, with very few exceptions, the literature supports the concept that patients with TIA and those with ischemic stroke should be treated the same in terms of secondary prevention.This guideline is divided into 4 sections:Diagnostic Evaluation for Secondary Stroke PreventionVascular Risk Factor ManagementManagement by EtiologySystems of Care for Secondary Ischemic Stroke Prevention.The structure and scope of this guideline differ from those of the 2014 Guidelines for the prevention of stroke in patients with stroke and TIA9 in several ways. First, the current guideline reflects numerous innovations and modifications that were incorporated into the AHA clinical practice guideline format. Introduced in 2017, modifications to AHA guidelines included making the text shorter and more user friendly; focusing guidelines on recommendations and patient management flow diagrams and less on extensive text and background information; formatting guidelines so that they can be easily updated with guideline focused updates; and including “chunks” of information after each recommendation.23 Second, the Diagnostic Evaluation and Systems of Care for Secondary Prevention sections are new. The Diagnostic Evaluation for Secondary Stroke Prevention section focuses on the evidence base for laboratory and imaging studies for guiding secondary stroke prevention decisions. Often these tests are completed in the inpatient setting. The Systems of Care for Secondary Prevention section contains 3 subsections: (1) Health Systems–Based Interventions for Secondary Stroke Prevention, (2) Interventions Aimed at Changing Patient Behavior, and (3) Health Equity. The Health Equity subsection is a refocus of the 2014 guideline’s section guiding management of high-risk populations. Third, this guideline does not include a separate section on metabolic syndrome because there are no unique recommendations for metabolic syndrome aside from managing each of the individual components of the syndrome. Fourth, the section on alcohol use was expanded to include the use of other substances. Finally, several additional conditions were included in the Management by Etiology section: congenital heart disease, cardiac tumors, moyamoya disease, migraine, malignancy, vasculitis, other genetic disorders, carotid web, fibromuscular dysplasia, dolichoectasia, and embolic stroke of undetermined source (ESUS).In developing the 2021 secondary stroke prevention guideline, the writing group reviewed prior published AHA/ASA guidelines and scientific statements. Table 2 contains a list of these other guidelines and statements deemed pertinent to this writing effort and is intended for use as a reader resource, thus reducing the need to repeat existing guideline recommendations.Table 2. Associated AHA/ASA Guidelines and StatementsTitleOrganizationPublication yearAHA/ASA guidelines Guidelines for Carotid Endarterectomy24AHA/ASA1998 Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease25ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS2011 Guideline on Lifestyle Management to Reduce Cardiovascular Risk26AHA/ACC2013 Guideline for the Management of Overweight and Obesity in Adults27AHA/ACC/TOS2013 Guideline for the Management of Patients With Atrial Fibrillation28AHA/ACC/HRS2014 Guidelines for the Management of Spontaneous Intracerebral Hemorrhage17AHA/ASA2014 Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack9AHA/ASA2014 Guidelines for the Prevention of Stroke in Women20AHA/ASA2014 Guidelines for the Primary Prevention of Stroke18AHA/ASA2014 Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults29ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA2017 Guideline for the Management of Adults With Congenital Heart Disease30AHA/ACC2018 Guideline on the Management of Blood Cholesterol31AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke16AHA/ASA2019 Guideline on the Primary Prevention of Cardiovascular Disease19ACC/AHA2019 Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation32AHA/ACC/HRS2019 Guideline for the Management of Patients With Valvular Heart Disease33ACC/AHA2020AHA/ASA statements Diagnosis and Management of Cerebral Venous Thrombosis22AHA/ASA2011 Cervical Arterial Dissections and Association With Cervical Manipulative Therapy21AHA/ASA2014 Physical Activity and Exercise Recommendations for Stroke Survivors34AHA/ASA2014 Spontaneous Coronary Artery Dissection: Current State of the Science34aAHA/ASA2018AHA/ASA presidential advisory Defining Optimal Brain Health in Adults35AHA/ASA2017AACVPR indicates American Association of Cardiovascular and Pulmonary Rehabilitation; AANN, American Association of Neuroscience Nurses; AANS, American Association of Neurological Surgeons; AAPA, American Academy of Physician Assistants; ABC, Association of Black Cardiologists; ACC, American College of Cardiology; ACCF, American College of Cardiology Foundation; ACPM, American College of Preventive Medicine; ACR, American College of Radiology; ADA, American Diabetes Association; AGS, American Geriatrics Society; AHA, American Heart Association; ASA, American Stroke Association; APhA, American Pharmacists Association; ASH, American Society of Hypertension; ASNR, American Society of Neuroradiology; ASPC, American Society for Preventive Cardiology; CNS, Congress of Neurological Surgeons; HRS, Heart Rhythm Society; NLA, National Lipid Association; NMA, National Medical Association; PCNA, Preventive Cardiovascular Nurses Association; SAIP, Society of Atherosclerosis Imaging and Prevention; SCAI, Society for Cardiovascular Angiography and Interventions; SIR, Society of Interventional Radiology; SNIS, Society of NeuroInterventional Surgery; SVM, Society for Vascular Medicine; SVS, Society for Vascular Surgery; and TOS, The Obesity Society.1.5. Class of Recommendation and Level of EvidenceRecommendations are designated both a Class of Recommendation (COR) and a Level of Evidence (LOE). The COR indicates the strength of recommendation, encompassing the estimated magnitude and certainty of benefit in proportion to risk. The LOE rates the quality of scientific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 3).Table 3. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)*Table 3. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care (Updated May 2019)*Numerous studies have evaluated strategies for stroke prevention in individuals without a history of stroke/TIA (ie, primary prevention studies) or included individuals with a history of stroke/TIA mixed into the pools of patients studied in smaller numbers. After carefully reviewing the literature and discussing with AHA methodologists, the writing group decided that many of these prevention strategies were important to include in any guideline on the prevention of recurrent stroke. There is often no reason to think that the mechanism of stroke prevention and benefits would be different in primary versus secondary prevention, although not studied within a purely secondary stroke prevention trial. Therefore, this writing group occasionally includes recommendations with evidence based in the primary prevention of atherosclerotic cardiovascular disease (ASCVD), atherosclerosis, or combined end points of cardiac disease and stroke in this guideline.To acknowledge that some studies were not performed in a purely ischemic stroke population, the LOE was downgraded. In this way, the writing group agreed that this would provide the best and most complete recommendations to the clinician about important strategies for secondary stroke prevention. Principles guiding inclusion and extrapolation of the results of these studies were as follows:The quality of the trial/trials was acceptable.(Ideally, stroke or TIA occurrence or recurrence was a prespecified end point, with clear protocols for assessing stroke end points.)From a physiological perspective, the primary prevention strategy used in the study will likely be effective for secondary prevention.Patients with ischemic stroke were included in the population studied when possible.1.6. AbbreviationsAbbreviationMeaning/PhraseACCAmerican College of CardiologyACSacute coronary syndromeACTIVE WAtrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular EventsAFatrial fibrillationAHAAmerican Heart AssociationAHIapnea-hypopnea indexARCHAortic Arch Related Cerebral Hazard TrialARISTOTLEApixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial FibrillationASAAmerican Stroke AssociationASAPAddressing Sleep Apnea Post Stroke/TIAASTRO-APSApixaban for Secondary Prevention of Thromboembolism Among Patients With Antiphospholipid SyndromeASCVDatherosclerotic cardiovascular diseaseBMIbody mass indexBPblood pressureBUST-StrokeBreaking Up Sitting Time After StrokeCADISSCervical Artery Dissection in Stroke StudyCARDIACoronary Artery Risk Development in Young AdultsCAPContinued Access RegistryCAPRIEClopidogrel Versus Aspirin in Patients at Risk of Ischaemic EventsCAScarotid artery stentingCATHARSISCilostazol-Aspirin Therapy Against Recurrent Stroke With Intracranial Artery StenosisCEAcarotid endarterectomyCHANCEClopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular EventsCICASChinese Intracranial AtherosclerosisCLAIRClopidogrel Plus Aspirin for Infarction ReductionCLOSEPatent Foramen Ovale Closure or Anticoagulants Versus Antiplatelet Therapy to Prevent Stroke RecurrenceCNScentral nervous systemCOMMANDER HFA Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart FailureCOMPASSCardiovascular Outcomes for People Using Anticoagulation StrategiesCORClass of RecommendationCOSSCarotid Occlusion Surgery StudyCPAPcontinuous positive airway pressureCRESTCarotid Revascularization Endarterectomy versus Stenting TrialCSPSCilostazol for Prevention of Secondary StrokeCTcomputed tomographyCTAcomputed tomographic angiographyCVDcardiovascular diseaseDAPTdual antiplatelet therapyDASHDietary Approaches to Stop HypertensionDCCTDiabetes Control and Complication TrialDESERVEDischarge Educational Strategies for Reduction of Vascular EventsDHAdocosahexaenoic acidDiRECTDiabetes Remission Clinical TrialDOACdirect-acting oral anticoagulantECSTEuropean Carotid Surgery TrialEFejection fractionENGAGE AF-TIMI 48Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs Standard Practice of Dosing With Warfarin in Patients With Atrial FibrillationEPAeicosapentaenoic acidEPIC-CVDEuropean Prospective Investigation into Cancer and Nutrition-CVD case-cohort studyESH-CHL-SHOTEuropean Society of Hypertension and Chinese Hypertension League Stroke in Hypertension Optimal Treatment TrialESPRITEuropean/Australasian Stroke Prevention in Reversible Ischaemia TrialESPS2Second European Stroke Prevention StudyESUSembolic stroke of undetermined sourceExStrokePhysical Exercise After Acute Ischaemic StrokeFASTESTEfficacy and Safety of a TIA/Stroke Electronic Support ToolFMDfibromuscular dysplasiaFOURIERFurther Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated RiskGELIAGerman Experience With Low Intensity AnticoagulationGLP-1glucagon-like protein 1HbA1chemoglobin A1cHRhazard ratioICAinternal carotid arteryICARUSSIntegrated Care for the Reduction of Secondary StrokeICASintracranial atherosclerotic stenosisICHintracerebral hemorrhageIEinfective endocarditisIMPROVE-ITImproved Reduction of Outcomes: Vytorin Efficacy International TrialINRinternational normalized ratioINSPiRE-TMSIntensified Secondary Prevention Intending a Reduction of Recurrent Events in TIA and Minor Stroke PatientsIPEicosapent ethylIRISInsulin Resistance Intervention After StrokeJAMJapan Adult MoyamoyaJELISJapan EPA Lipid Intervention StudyLDLlow-density lipoproteinLDL-Clow-density lipoprotein cholesterolLOELevel of EvidenceLVleft ventricularLVADleft ventricular assist devicesMACEmajor adverse cardiovascular eventMDmean differenceMImyocardial infarctionMISTMotivational Interviewing in StrokeMRAmagnetic resonance angiographyMRImagnetic resonance imagingNAILED StrokeNurse Based Age Independent Intervention to Limit Evolution of Disease After StrokeNASCETNorth American Symptomatic Carotid Endarterectomy TrialNAVIGATE ESUSRivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Systemic Embolism in Patients With Recent Embolic Stroke of Undetermined SourceNIHSSNational Institutes of Health Stroke ScaleODYSSEY OUTCOMESEvaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With AlirocumabOMEMIOmega-3 Fatty Acids in Elderly Patients With Acute Myocardial InfarctionORodds ratioOSAobstructive sleep apneaOXVASCOxford Vascular StudyPARpopulation-attributable riskPAST-BPPrevention After Stroke–Blood PressurePCSK9proprotein convertase subtilisin/kexin type 9PFOpatent foramen ovalePODCASTPrevention of Decline in Cognition after Stroke TrialPOINTPlatelet-Oriented Inhibition in New TIA and Minor Ischemic StrokePRAISEPrevent Recurrence of All Inner-City Strokes Through EducationPREDIMEDPrevención con Dieta MediterráneaPREVAILProspective Randomised Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrill