AHA/ASA GUIDELINE
`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
`Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and
`Congress of Neurological Surgeons.
`Endorsed by the Society of Vascular and Interventional Neurology
`The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists.
`
`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. Williams, MD, FAHA
`Key Words: AHA Scientific Statements ◼ ischemic attack, transient ◼ secondary prevention ◼ stroke
`
`TOP 10 TAKE-HOME MESSAGES FOR
`THE SECONDARY STROKE PREVENTION
`GUIDELINE
`1. Specific recommendations for prevention strate-
`gies often depend on the ischemic stroke/tran-
`sient ischemic attack subtype. Therefore, new in
`this guideline is a section describing recommen-
`dations 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.
`2. Management of vascular risk factors remains
`extremely important in secondary stroke preven-
`tion, including (but not limited to) diabetes, smok-
`ing 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.
`
`3. Lifestyle factors, including healthy diet and physi-
`cal activity, are important for preventing a second
`stroke. Low-salt and Mediterranean diets are rec-
`ommended 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 super-
`vised and safe manner.
`4. 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.
`5. 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 sec-
`ondary stroke prevention. Dual antiplatelet therapy
`is not recommended long term, and short term, dual
`
`
`*AHA Stroke Council Scientific Statement Oversight Committee on Clinical Practice Guidelines Liaison.
`†AAN Representative.
`AHA Stroke Council Scientific Statement Oversight Committee Members, see page e436.
`© 2021 American Heart Association, Inc.
`Stroke is available at www.ahajournals.org/journal/str
`
`Stroke. 2021;52:e364–e467. DOI: 10.1161/STR.0000000000000375
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`July 2021
`
` e364
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`Stroke
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`antiplatelet therapy is recommended only in very
`specific patients, including those with early arriv-
`ing minor stroke and high-risk transient ischemic
`attack or severe symptomatic intracranial stenosis.
`6. 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 usu-
`ally recommended if no other cause of stroke is
`discovered.
`7. 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 comor-
`bidities and features of their vascular anatomy.
`8. 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 recur-
`rence. Aggressive medical management of risk
`factors and short-term dual antiplatelet therapy are
`preferred.
`9. There have been several studies evaluating sec-
`ondary 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.
`10. Patients with embolic stroke of uncertain source
`should not be treated empirically with anticoagu-
`lants or ticagrelor because it was found to be of no
`benefit.
`
`PREAMBLE
`Since 1990, the American Heart Association (AHA)/
`American Stroke Association (ASA)* have translated sci-
`entific evidence into clinical practice guidelines with rec-
`ommendations 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 mem-
`bers volunteer their time to the writing and review efforts.
`Clinical practice guidelines for stroke provide rec-
`ommendations applicable to patients with or at risk of
`
`*The American Stroke Association is a division of the American Heart Association.
`
`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’ inter-
`ests. 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 differ-
`ent 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 endors-
`ers. 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 recom-
`mendations, 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 supple-
`ment (Data Supplement) for useful but noncritical tables
`and figures.
`
`Sepideh Amin-Hanjani, MD, FAHA
`Immediate Past Chair, AHA Stroke Council Scientific
`Statement Oversight Committee
`Joseph P. Broderick, MD, FAHA
`Chair, AHA Stroke Council Scientific Statement
`Oversight Committee
`
`1. INTRODUCTION
`Each year, ≈795 000 individuals in the United States
`experience a stroke, of which 87% (690 000) are isch-
`emic 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
`
`Stroke. 2021;52:e364–e467. DOI: 10.1161/STR.0000000000000375
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`July 2021
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` e365
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`CLINICAL STATEMENTS
`
` AND GUIDELINES
`
`Kleindorfer et al
`
`2021 Guideline for the Secondary Prevention of Ischemic Stroke
`
`Downloaded from http://ahajournals.org by on January 16, 2024
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`prevention. In fact, cohort studies have shown a reduc-
`tion 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 ther-
`apy.5 The changes may have been influenced by changes
`in diagnostic criteria and differing sensitivities of diag-
`nostic tests over the years.
`The overwhelming majority of strokes can be pre-
`vented through BP control, a healthy diet, regular physi-
`cal activity, and smoking cessation. In fact, 5 factors—BP,
`diet, physical inactivity, smoking, and abdominal obe-
`sity—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 medi-
`cations, combined with diet modification and exercise,
`can result in an 80% cumulative risk reduction in recur-
`rent vascular events.7 Although the benefits of a healthy
`lifestyle and vascular risk factor control are well docu-
`mented,8,9 risk factors remain poorly controlled among
`stroke survivors.10–14
`
`1.1. Methodology and Evidence Review
`This 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 dissemina-
`tion of information by using concise language and for-
`matting. 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, pub-
`lished in English, and indexed in MEDLINE, PubMed,
`Cochrane Library, and other selected databases rel-
`evant 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 Sup-
`plement, which also contains the final evidence tables
`that summarize the evidence used by the guideline writ-
`ing 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.
`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 sec-
`tion material. All recommendations were fully reviewed
`and discussed among the full committee to allow diverse
`perspectives and considerations for this guideline. Rec-
`ommendations were then voted on to reach consensus.
`The systematic review has been published in conjunc-
`tion with this guideline and includes its respective data
`supplements.15
`
`1.2. Organization of the Writing Group
`The writing group consisted of neurologists, neurological
`surgeons, cardiologists, internists, and a lay/patient rep-
`resentative. The writing group included representatives
`from the AHA/ASA and the American Academy of Neu-
`rology. Appendix 1 lists writing group members’ relevant
`relationships with industry and other entities. For the pur-
`poses of full transparency, the writing group members’
`comprehensive disclosure information is available online.
`
`1.3. Document Review and Approval
`This document was reviewed by the AHA’s Stroke Coun-
`cil Scientific Statement Oversight Committee; the AHA’s
`Science Advisory and Coordinating Committee; the
`AHA’s Executive Committee; reviewers from the Ameri-
`can Academy of Neurology, from the Society of Vascu-
`lar and Interventional Neurology, and from the American
`Association of Neurological Surgeons and Congress of
`Neurological Surgeons; as well as by 55 individual con-
`tent 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.
`
`e366
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`Stroke. 2021;52:e364–e467. DOI: 10.1161/STR.0000000000000375
`
`Kleindorfer et al
`
`2021 Guideline for the Secondary Prevention of Ischemic Stroke
`
`CLINICAL STATEMENTS
`
`AND GUIDELINES
`
`Downloaded from http://ahajournals.org by on January 16, 2024
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`Table 1. Evidence Review Committee Question
`
`Question
`No.
`
`1
`
`Question
`
`In 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?
`
`Section No.
`
`5.19
`
`DAPT indicates dual antiplatelet therapy; and TIA, transient ischemic attack.
`
`1.4. Scope of the Guideline
`The aim of the present guideline is to provide clinicians
`with evidence-based recommendations for the preven-
`tion 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),
`for stroke prevention
`• Special considerations
`in women (covered in the “Guidelines for the
`Prevention of Stroke in Women”20), and
`• Cerebral venous sinus thrombosis (covered in
`“Diagnosis and Management of Cerebral Venous
`Thrombosis”22).
`In general, with very few exceptions, the literature sup-
`ports 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:
`
` 1. Diagnostic Evaluation for Secondary Stroke
`Prevention
` 2. Vascular Risk Factor Management
` 3. Management by Etiology
` 4. Systems 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 innova-
`tions 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 guide-
`lines on recommendations and patient management
`
`flow diagrams and less on extensive text and back-
`ground information; formatting guidelines so that they
`can be easily updated with guideline focused updates;
`and including “chunks” of information after each rec-
`ommendation.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 com-
`pleted 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 Chang-
`ing 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 syn-
`drome. 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, vas-
`culitis, other genetic disorders, carotid web, fibromus-
`cular 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.
`
`1.5. Class of Recommendation and Level of
`Evidence
`Recommendations are designated both a Class of Rec-
`ommendation (COR) and a Level of Evidence (LOE). The
`COR indicates the strength of recommendation, encom-
`passing the estimated magnitude and certainty of benefit
`in proportion to risk. The LOE rates the quality of scien-
`tific evidence supporting the intervention on the basis of
`the type, quantity, and consistency of data from clinical
`trials and other sources (Table 3).
`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 care-
`fully reviewing the literature and discussing with AHA
`methodologists, the writing group decided that many of
`these prevention strategies were important to include
`
`Stroke. 2021;52:e364–e467. DOI: 10.1161/STR.0000000000000375
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`July 2021
`
` e367
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`CLINICAL STATEMENTS
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` AND GUIDELINES
`
`Kleindorfer et al
`
`2021 Guideline for the Secondary Prevention of Ischemic Stroke
`
`Downloaded from http://ahajournals.org by on January 16, 2024
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`Table 2. Associated AHA/ASA Guidelines and Statements
`
`Title
`
`AHA/ASA guidelines
`
`Organization
`
`Publication year
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Guideline for the Management of Patients With Valvular Heart Disease33
`
`AHA/ASA statements
`
`
`
`
`
`
`
` Diagnosis and Management of Cerebral Venous Thrombosis22
`
` Cervical Arterial Dissections and Association With Cervical Manipulative Therapy21
`
` Physical Activity and Exercise Recommendations for Stroke Survivors34
`
` Spontaneous Coronary Artery Dissection: Current State of the Science34a
`
`AHA/ASA presidential advisory
`
`
`
` Defining Optimal Brain Health in Adults35
`
` Guidelines for Carotid Endarterectomy24
`
` Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease25
`
` Guideline on Lifestyle Management to Reduce Cardiovascular Risk26
`
` Guideline for the Management of Overweight and Obesity in Adults27
`
` Guideline for the Management of Patients With Atrial Fibrillation28
`
` Guidelines for the Management of Spontaneous Intracerebral Hemorrhage17
`
` Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack9
`
` Guidelines for the Prevention of Stroke in Women20
`
` Guidelines for the Primary Prevention of Stroke18
`
` Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults29
`
` Guideline for the Management of Adults With Congenital Heart Disease30
`
` Guideline on the Management of Blood Cholesterol31
`
` Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018
`Guidelines for the Early Management of Acute Ischemic Stroke16
`
` Guideline on the Primary Prevention of Cardiovascular Disease19
`
`AHA/ASA
`
`ASA/ACCF/AHA/AANN/
`AANS/ACR/ASNR/CNS/
`SAIP/SCAI/SIR/SNIS/
`SVM/SVS
`
`AHA/ACC
`
`AHA/ACC/TOS
`
`AHA/ACC/HRS
`
`AHA/ASA
`
`AHA/ASA
`
`AHA/ASA
`
`AHA/ASA
`
`ACC/AHA/AAPA/ABC/
`ACPM/AGS/APhA/ASH/
`ASPC/NMA/PCNA
`
`AHA/ACC
`
`AHA/ACC/AACVPR/AAPA/
`ABC/ACPM/ADA/AGS/
`APhA/ASPC/NLA/PCNA
`
`AHA/ASA
`
`ACC/AHA
`
` Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation32
`
`AHA/ACC/HRS
`
`1998
`
`2011
`
`2013
`
`2013
`
`2014
`
`2014
`
`2014
`
`2014
`
`2014
`
`2017
`
`2018
`
`2018
`
`2019
`
`2019
`
`2019
`
`2020
`
`2011
`
`2014
`
`2014
`
`2018
`
`
`
`2017
`
`ACC/AHA
`
`AHA/ASA
`
`AHA/ASA
`
`AHA/ASA
`
`AHA/ASA
`
`
`
`AHA/ASA
`
`AACVPR 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 Cardiol-
`ogy; 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.
`
`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 pri-
`mary versus secondary prevention, although not studied
`within a purely secondary stroke prevention trial. There-
`fore, this writing group occasionally includes recommen-
`dations with evidence based in the primary prevention of
`atherosclerotic cardiovascular disease (ASCVD), athero-
`sclerosis, 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 down-
`graded. 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 extrapo-
`lation of the results of these studies were as follows:
`1. 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.)
`2. From a physiological perspective, the primary pre-
`vention strategy used in the study will likely be
`effective for secondary prevention.
`3. Patients with ischemic stroke were included in the
`population studied when possible.
`
`e368
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` July 2021
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`Stroke. 2021;52:e364–e467. DOI: 10.1161/STR.0000000000000375
`
`Kleindorfer et al
`
`2021 Guideline for the Secondary Prevention of Ischemic Stroke
`
`CLINICAL STATEMENTS
`
`AND GUIDELINES
`
`Downloaded from http://ahajournals.org by on January 16, 2024
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`1.6. Abbreviations
`Abbreviation
`Meaning/Phrase
`
`ACC
`ACS
`ACTIVE W
`
`AF
`AHA
`AHI
`ARCH
`ARISTOTLE
`
`ASA
`ASAP
`ASTRO-APS
`
`ASCVD
`BMI
`BP
`BUST-Stroke
`CADISS
`CARDIA
`CAP
`CAPRIE
`
`CAS
`CATHARSIS
`
`CEA
`CHANCE
`
`CICAS
`CLAIR
`CLOSE
`
`CNS
`COMMANDER
`HF
`
`COMPASS
`
`COR
`COSS
`CPAP
`CREST
`
`CSPS
`CT
`CTA
`CVD
`DAPT
`DASH
`DCCT
`DESERVE
`
`American College of Cardiology
`acute coronary syndrome
`Atrial Fibrillation Clopidogrel Trial With Irbesartan for
`Prevention of Vascular Events
`atrial fibrillation
`American Heart Association
`apnea-hypopnea index
`Aortic Arch Related Cerebral Hazard Trial
`Apixaban for Reduction in Stroke and Other Thrombo-
`embolic Events in Atrial Fibrillation
`American Stroke Association
`Addressing Sleep Apnea Post Stroke/TIA
`Apixaban for Secondary Prevention of Thromboembo-
`lism Among Patients With Antiphospholipid Syndrome
`atherosclerotic cardiovascular disease
`body mass index
`blood pressure
`Breaking Up Sitting Time After Stroke
`Cervical Artery Dissection in Stroke Study
`Coronary Artery Risk Development in Young Adults
`Continued Access Registry
`Clopidogrel Versus Aspirin in Patients at Risk of
`Ischaemic Events
`carotid artery stenting
`Cilostazol-Aspirin Therapy Against Recurrent Stroke
`With Intracranial Artery Stenosis
`carotid endarterectomy
`Clopidogrel in High-Risk Patients With Acute Non-
`Disabling Cerebrovascular Events
`Chinese Intracranial Atherosclerosis
`Clopidogrel Plus Aspirin for Infarction Reduction
`Patent Foramen Ovale Closure or Anticoagulants Ver-
`sus Antiplatelet Therapy to Prevent Stroke Recurrence
`central nervous system
`A 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 Failure
`Cardiovascular Outcomes for People Using Anticoagu-
`lation Strategies
`Class of Recommendation
`Carotid Occlusion Surgery Study
`continuous positive airway pressure
`Carotid Revascularization Endarterectomy versus
`Stenting Trial
`Cilostazol for Prevention of Secondary Stroke
`computed tomography
`computed tomographic angiography
`cardiovascular disease
`dual antiplatelet therapy
`Dietary Approaches to Stop Hypertension
`Diabetes Control and Complication Trial
`Discharge Educational Strategies for Reduction of
`Vascular Events
`
`Abbreviation
`
`Meaning/Phrase
`
`DHA
`DiRECT
`DOAC
`ECST
`EF
`ENGAGE
`AF-TIMI 48
`
`EPA
`EPIC-CVD
`
`ESH-CHL-SHOT
`
`ESPRIT
`
`ESPS2
`ESUS
`ExStroke
`FASTEST
`FMD
`FOURIER
`
`GELIA
`GLP-1
`HbA1c
`HR
`ICA
`ICARUSS
`ICAS
`ICH
`IE
`IMPROVE-IT
`
`INR
`INSPiRE-TMS
`
`IPE
`IRIS
`JAM
`JELIS
`LDL
`LDL-C
`LOE
`LV
`LVAD
`MACE
`MD
`MI
`MIST
`MRA
`MRI
`NAILED Stroke
`
`docosahexaenoic acid
`Diabetes Remission Clinical Trial
`direct-acting oral anticoagulant
`European Carotid Surgery Trial
`ejection fraction
`Global Study to Assess the Safety and Effective-
`ness of Edoxaban (DU-176b) vs Standard Practice
`of Dosing With Warfarin in Patients With Atrial
`Fibrillation
`eicosapentaenoic acid
`European Prospective Investigation into Cancer and
`Nutrition-CVD case-cohort study
`European Society of Hypertension and Chinese
`Hypertension League Stroke in Hypertension Optimal
`Treatment Trial
`European/Australasian Stroke Prevention in Reversible
`Ischaemia Trial
`Second European Stroke Prevention Study
`embolic stroke of undetermined source
`Physical Exercise After Acute Ischaemic Stroke
`Efficacy and Safety of a TIA/Stroke Electronic Support Tool
`fibromuscular dysplasia
`Further Cardiovascular Outcomes Research With
`PCSK9 Inhibition in Subjects With Elevated Risk
`German Experience With Low Intensity Anticoagulation
`glucagon-like protein 1
`hemoglobin A1c
`hazard ratio
`internal carotid artery
`Integrated Care for the Reduction of Secondary Stroke
`intracranial atherosclerotic stenosis
`intracerebral hemorrhage
`infective endocarditis
`Improved Reduction of Outcomes: Vytorin Efficacy
`International Trial
`international normalized ratio
`Intensified Secondary Prevention Intending a Reduction
`of Recurrent Events in TIA and Minor Stroke Patients
`icosapent ethyl
`Insulin Resistance Intervention After Stroke
`Japan Adult Moyamoya
`Japan EPA Lipid Intervention Study
`low-density lipoprotein
`low-density lipoprotein cholesterol
`Level of Evidence
`left ventricular
`left ventricular assist devices
`major adverse cardiovascular event
`mean difference
`myocardial infarction
`Motivational Interviewing in Stroke
`magnetic resonance angiography
`magnetic resonance imaging
`Nurse Based Age Independent Intervention to Limit
`Evolution of Disease After Stroke
`
`Stroke. 2021;52:e364–e467. DOI: 10.1161/STR.0000000000000375
`
`July 2021
`
` e369
`
`CLINICAL STATEMENTS
`
` AND GUIDELINES
`
`Kleindorfer et al
`
`2021 Guideline for the Secondary Prevention of Ischemic Stroke
`
`Downloaded from http://ahajournals.org by on January 16, 2024
`
`Novo Nordisk Exhibit 2099
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00006
`
`

`

`Abbreviation
`
`Meaning/Phrase
`
`Abbreviation
`
`Meaning/Phrase
`
`NASCET
`
`NIHSS
`ODYSSEY
`OUTCOMES
`OMEMI
`
`OR
`OSA
`OXVASC
`PAR
`PAST-BP
`PCSK9
`PFO
`PODCAST
`POINT
`
`PRAISE
`
`PREDIMED
`PREVAIL
`
`North American Symptomatic Carotid Endarterectomy
`Trial
`NAVIGATE ESUS Rivaroxaban Versus Aspirin in Secondary Prevention
`of Stroke and Prevention of Systemic Embolism in
`Patients With Recent Embolic Stroke of Undetermined
`Source
`National Institutes of Health Stroke Scale
`Evaluation of Cardiovascular Outcomes After an Acute
`Coronary Syndrome During Treatment With Alirocumab
`Omega-3 Fatty Acids in Elderly Patients With Acute
`Myocardial Infarction
`odds ratio
`obstructive sleep apnea
`Oxford Vascular Study
`population-attributable risk
`Prevention After Stroke–Blood Pressure
`proprotein convertase subtilisin/kexin type 9
`patent foramen ovale
`Prevention of Decline in Cognition after Stroke Trial
`Platelet-Oriented Inhibition in New TIA and Minor
`Ischemic Stroke
`Prevent Recurrence of All Inner-City Strokes Through
`Education
`Prevención con Dieta Mediterránea
`Prospective Randomised Evaluation of the Watchman
`LAA Closure Device in Patients With Atrial Fibrillation
`Versus Long Term Warfarin Therapy
`Preventing Recurrent Vascular Events in Patients With
`Stroke or Transient Ischemic Attack
`Prevention Regimen for Effectively Avoiding Second
`Strokes
`Watchman Left Atrial Appendage System for Embolic
`Protection in Patients With Atrial Fibrillation
`percutaneous transluminal angioplasty and stenting
`randomized controlled trial
`Randomized, Phase II Study to Evaluate the Safety
`and Pharmacokinetics of Oral Dabigatran Etexilate in
`Patients After Heart Valve Replacement
`Ran