Finally, although DOACs may be beneficial in vascular event reduction in patients with stable CVD (COMPASS [Cardiovascular Outcomes for People Using Antico- whether they have any role in secondary stroke prevention for patients with recent noncardioembolic stroke remains an unanswered question. In summary, further research is needed in the following areas: Optimal combination of medications, timing of initia- tion, and duration of DAPT. Effectiveness and potential harm of DAPT among specific subgroups of patients according to stroke characteristics, laboratory or genetic tests, or other factors. Effectiveness/selection of a given antiplatelet agent over another in specific subgroups of patients with noncardioembolic stroke. Benefit of switching antiplatelet agent for patients already taking 1 antiplatelet medication at the time of stroke. Effectiveness of DOACs compared with or in com- bination with antiplatelet therapy for secondary stroke prevention among patients with noncardio- embolic ischemic stroke. 6. SYSTEMS OF CARE FOR SECONDARY PREVENTION 6.1. Health Systems Based Interventions for Secondary Stroke Prevention Recommendations for Health Systems Based Interventions Referenced studies that support recommendations are summarized in online Data Supplements 60 62. COR LOE Recommendations In patients with ischemic stroke or TIA, voluntary hospital-based or outpatient-focused quality monitoring and improvement programs are recommended to improve short-term and long-term adherence to nationally accepted, evidence-based guidelines for secondary stroke prevention. In patients with ischemic stroke or TIA, a mul- tidisciplinary outpatient team-based approach (ie, care provision with active medication adjust- ment from advanced practice providers, nurses, or pharmacists) can be effective to control BP, lipids, and other vascular risk factors.810 817 In patients presenting to their primary care provider as the first contact after TIA or minor stroke, it is reasonable to use a decision sup- port tool that improves diagnostic accuracy, stratifies patients in risk categories to support appropriate triage, and prompts the initiation of medications and counseling for lifestyle modification for secondary stroke prevention to reduce the 90-day risk of recurrent stroke Synopsis Optimal treatment recommendations exist for many stroke risk factors. However, treatment targets are often unmet after ischemic stroke and TIA, thereby increasing the risk of recurrent events.819 825 Health system approaches to acute stroke management have transformed care delivery and have led to improved access to stroke treatment and improved stroke outcomes.826 828 Similar approaches to poststroke care and secondary prevention hold promise for improving risk factor control after stroke.829 Risk factor control is affected by patient, provider, and system-level factors. We define health systems-based interventions CLINICAL STATEMENTS AND GUIDELINES Kleindorfer for secondary stroke prevention as those that influence vascular risk factor treatment and control by influencing provider or patient behaviors. These are often multicom- ponent interventions that fit into categories defined by Wensing et al829 and referenced in a Cochrane review of interventions for secondary stroke prevention.830 Cat- egories include interventions that involve revision of pro- fessional roles, collaboration between multidisciplinary teams, integrated care services, knowledge management systems, and quality management systems. We review best available data here but consider that the generaliz- ability of findings may be affected by the study setting, patient access to care after an acute stroke, and other patient demographic characteristics. Recommendation-Specific Supportive Text 1. Adherence to evidence-based guidelines for secondary stroke prevention is affect by health system level, hospital-level, provider-level, and patient- and community-specific factors. Regular hospital and outpatient-based programs for adher- ence and risk factor monitoring provide the oppor- tunity to identify areas of need and to optimize strategies to improve care quality, improve risk fac- tor control, and ultimately reduce the risk of recur- rent stroke and TIA. The Get With The Guidelines registry is an example of an inpatient registry used for quality monitoring and improvement.831 2. Interventions that include a multidisciplinary team based approach to care may be beneficial for risk factor control and secondary prevention after ischemic stroke and TIA. In the ICARUSS study (Integrated Care for the Reduction of Secondary Stroke) conducted in Australia, an integrated shared-care model intervention was associated with a significant decrease in SBP at 12 months compared with usual care.810,811 Several additional studies, including NAILED Stroke (Nurse Based Age Independent Intervention to Limit Evolution of Disease After Stroke; Sweden) and PREVENTION (Preventing Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack; Canada), showed significant benefit for BP lowering when nurses or pharmacists were involved in BP man- In the SUSTAIN study (Systemic Use of Stroke Averting Interventions), investigators tested an intervention that included a nurse prac- titioner/physician assistant care manager, group clinics, self-management support, and care coordi- nation to enhance risk factor control. There was no between-group difference in the primary outcome of mean SBP; however, the intervention group was more likely to achieve LDL goals compared with the usual care group.815 Additional evidence for the benefit of team-based interventions for secondary prevention of stroke is derived from nonrandomized data. In Ontario, Canada, Stroke Prevention Clinics evolved as an interdisciplinary approach to stroke assessment, prevention, and risk factor manage- Patients are referred to these clinics from their primary doctors after TIA or after emergency department visit for TIA or stroke. Care in these clinics has been associated with increased use of evidence-based strategies for stroke prevention and decreased risk of mortality at 1 year compared with patients who are not referred to such clinics.816 In the COMPASS pragmatic trial (United States), there was no benefit of a stroke transitional care model on secondary behavioral outcomes for risk factor control; however, implementation of the model into real-world practice was a major barrier. Additional ongoing and recently completed randomized trials are evaluating the impact of team-based interven- tions on risk factor control and secondary preven- tion after ischemic stroke and TIA.833 838 3. In the FASTEST study (Efficacy and Safety of a Transient Ischaemic Attack [TIA] Electronic Support Tool) conducted in New Zealand, use of an elec- tronic decision support tool for TIA and stroke man- agement by general practitioners was compared with usual care for patients presenting to their gen- eral practitioner as first care contact after stroke or The tool was designed to improve diagnostic accuracy, to support appropriate triage, and to guide providers in appropriate medication and nonphar- macological (lifestyle counseling) management. TIA and stroke recurrence at 90 days was significantly lower in the intervention group compared with the usual care group, and patients receiving the intervention were more likely to receive guideline- adherent care. This study provides evidence for the use of an electronic decision support tool to guide primary care providers in the management of TIA or minor stroke. Knowledge Gaps and Future Research More research is needed to determine the most effective models of postacute care to address risk factor control and secondary stroke prevention in stroke survivors. The following knowledge gaps are highlighted: Effective transitions of care from the acute setting to the community affect access to postacute care for secondary prevention. Research on the most effective transitions of care strategies for second- ary stroke prevention is needed. Many patients have multiple risk factors for recur- rent stroke. Health systems based interventions that address simultaneous control of multiple risk factors for secondary stroke prevention are needed. Patients who are uninsured and underinsured may have limited access to poststroke care. Interventions to improve care access and to mitigate the impact CLINICAL STATEMENTS AND GUIDELINES Kleindorfer of lack of insurance on poststroke risk factor con- trol and secondary stroke prevention are needed. Additional studies are needed to evaluate the impact of decision support tools on risk factor con- trol and secondary stroke prevention after stroke hospitalization. The impact of telemedicine on acute stroke care is well established.839 Although telemedicine offers many potential benefits over in-person care, patients with stroke may face multiple barriers to engaging in telemedicine, including cognitive impairment and physical disability. Research is needed to evaluate the impact of telemedicine on poststroke risk factor control and secondary stroke prevention. Once proven effective, interventions must be imple- mented across hospital and health systems in order to achieve desired outcomes. Research that exam- ines the implementation of interventions across health systems is needed. 6.2. Interventions Aimed at Changing Patient Behavior Recommendations for Behavior Change Interventions Referenced studies that support recommendations are summarized in online Data Supplements 63 and 64. COR LOE Recommendations In patients with ischemic stroke or TIA, behavior change interventions targeting stroke literacy, lifestyle factors, and medica- tion adherence are recommended to reduce In patients with ischemic stroke or TIA, teaching self-management skills or using behavior change theory (eg, motivational interviewing) can be ben- eficial in improving medication adherence.840 843 In patients with stroke or TIA, combined exercise-based and behavior change interven- tions are probably indicated in preference to behavior interventions alone, exercise interven- tions alone, or usual care to reduce physiologi- cal stroke risk factors such as SBP.111 113,829 In patients with TIA or nondisabling stroke, engagement in targeted secondary prevention programs (eg, cardiac rehabilitation programs or exercise and lifestyle counseling programs) can be beneficial to reduce risk factors and recurrent ischemic events.133,134 For patients with disabling stroke who are discharged from acute services, engaging in targeted secondary prevention programs (eg, an adapted cardiac rehabilitation program or struc- tured exercise including aerobic activity and healthy lifestyle counseling) can be beneficial to reduce vascular risk factors and mortality.111,844 Benefit B-R In patients with stroke or TIA, provision of health information or advice about stroke prevention is essential; however, information or advice alone, in the absence of a behavioral intervention, is not an effective means to change modifiable, lifestyle-related risk factors in order to reduce future ischemic events.129,829,845 Synopsis Hypertension, smoking, T2D, physical activity, diet, psy- chosocial factors, abdominal obesity, alcohol, cardiac causes, and apolipoproteins account for 91.5% of the PAR for ischemic stroke, similar across world regions, sexes, and ages.5a,846 One in 3 US citizens has at least 1 of these risk factors,847 which can be modulated by health behaviors, indicating a focus for stroke second- ary prevention and self-care.848 Changing entrenched behavior is difficult, and sustaining change over time is challenging. Several systematic reviews examine lifestyle interventions after stroke; optimal approaches to reduce recurrent stroke remain unknown.112,840,841,849 Guidance on changing behaviors associated with chronic disease at an individual level is available850 ; however, a Delphi consensus identified that interventions to self-manage lifestyle risk factors after stroke need to be contextual- ized to the capacities, needs, and personal priorities of the individual and their families.851 Lifestyle change after stroke is more attainable when the lifestyle counseling is interactive, the advantages of behavior change are perceived as beneficial, and the counselor has sufficient resources (eg, availability of healthcare professionals time; appropriate counseling materials; knowledge and skills), highlighting a training need for healthcare staff to ensure good-quality counseling and patients adherence to healthier behavior.852 Recommendation-Specific Supportive Text 1. Longer-term follow-up in behavioral interventions after stroke addressing recurrent events is lack- However, meta-analysis (from 4 iden- =0) demonstrates that multimodal interventions addressing active educa- tion about risk factors, medications, and medication compliance and interventions to modify 1 lifestyle risk factors decrease the odds of recurrent cardiac no significant difference in the odds of recurrent TIA/stroke was reported in this review.840 Two small multimodal RCTs show promise for reducing cardiovascular end points. However, the small trial numbers dictate that results must be interpreted with caution pending larger, more definitive trials. A 24-week Japanese RCT (N=70)134 compris- ing exercise, salt restriction, and nutrition advice compared with usual care terminated at a median follow-up of 2.9 years when the prespecified effi- cacy point for the intervention was reached for the primary end point (composite stroke death, cardiac death, and hospitalization for stroke recurrence, MI, angina pectoris, or peripheral artery disease; (adjusted HR, 0.194 [95% CI, 0.121 0.737]). Long-term effects (3.5 years) of an exercise and education program, compared with usual care in TIA or minor stroke patients (N=60), found that CLINICAL STATEMENTS AND GUIDELINES Kleindorfer within the intervention group, recurrent stroke, minor stroke, or TIA events were reduced com- pared with the usual care group (RR, 0.23 [95% CI, 0.07 0.72]; number needed to treat, 3) and a reduction in mortality associated with the inter- needed to treat, 8).131 2. Adhering to pharmacological secondary preven- tion strategies is an important self-care behavior in stroke secondary prevention. However, nonad- herence to medication regimens is reported in up to 40% of individuals with stroke.853 Multimodal interventions have been shown in a meta-analysis to improve compliance with antithrombotic medi- Self-management interventions have similarly shown a moder- ate effect size in adherence to prescribed sec- ondary prevention medications after stroke In the MIST phase III RCT (Motivational Interviewing in Stroke; N=386), improving adherence to secondary stroke preven- tion strategies through motivational interviewing demonstrated positive effects on self-reported medication adherence 9 months after stroke (RR, associated reduction in recurrent stroke (RR, 0.67 Assistive technology may play an emerging role. The SMS4Stroke (Short Messaging Service for Stroke) trial (N=200) showed an adjusted MD of 0.54 (95% CI, 0.22 0.85) in the Morisky Medication Adherence Scale score after 2 months of receiving short messaging service reminders for each dose of medication.843 3. Systematic reviews of lifestyle interventions com- pared with usual care after stroke identify favor- able effects on reducing BP.111,112 A mean SBP Subgroup analysis identified nonsignificant effects for behav- ior interventions alone, significant effects for cardiovascular exercise interventions (MD, 3.9 larger effects for combined exercise and lifestyle interventions (MD, 5.3 mmHg [95% CI, 9.0 to =46%; N=228). A systematic review of exercise-based interventions on cardiovascular risk factors after stroke113 reported similar reductions in SBP in addition to other physiological outcomes (fasting insulin and glucose and high-density lipoprotein cholesterol). Mean SBP reductions in exercise interventions with or without other inter- were greater than those observed with exercise A review of educational/behavioral interventions (excluding exercise) showed no effect on SBP.829 4. Cardiac rehabilitation reduces cardiovascular mortality in coronary heart disease.854 Emerging evidence supports its broad application in TIA/ nondisabling stroke populations. One small RCT (N=22) demonstrated superiority to usual care in risk profiles, perceived physical functioning, and mental health when patients with TIA/nondis- abling stroke access existing programs.133 A cohort study (N=80) of participants with TIA attending a 6-month cardiac rehabilitation program demon- strated a significant (26%) increase in the lowest mortality risk category of the Duke treadmill score and significant improvements in fitness, total cho- lesterol/high density lipoprotein ratios, waist cir- cumference, and BMI.132 Two RCTs demonstrated promising longer-term reductions in cardiovascular events. A mixed exercise program combined with education and lifestyle counseling (N=60) dem- onstrated reduced recurrent stroke or TIA events in the intervention group compared with the usual care control group (RR, 0.23 [95% CI, 0.07 0.72]) and a reduction in mortality (RR, 0.11 [95% CI, A tailored intervention of exercise, salt restriction, and nutrition advice for 24 weeks compared with usual care (N=70) was also associated with a reduction in the primary composite endpoint of cardiovascular outcome 5. The Cochrane nonpharmacological interventions (based on cardiac rehabilitation) review for pre- venting vascular events after stroke/TIA855 identi- fied 1 pilot RCT of cardiac rehabilitation compared with usual stroke care (N=48), demonstrating promising and statistically significant gains in vascular risk profiles and cardiovascular fitness. A systematic review of lifestyle interventions in stroke identified this study and 2 others broadly matching cardiac rehabilitation in their format and concluded that, although meta-analysis was not possible, all studies were associated with signifi- cant improvements in health profiles and manage- ment of risk,111 with this approach endorsed in the AHA/ASA physical activity and exercise recom- mendations for stroke survivors.34 A recent pro- spective cohort study with a matched subgroup comparison (N=609) evaluated a Stroke Recovery Programme with 3 components: physician visits, outpatient therapy, and modified cardiac rehabilita- tion consisting of group therapy of 4 to 5 patients with stroke directed by a specially trained physical therapist and physical therapy assistant compared with usual rehabilitation. Nonrandomized subgroup CLINICAL STATEMENTS AND GUIDELINES Kleindorfer analysis comparing Stroke Recovery Programme participants (n=76) and matched pairs of nonpar- ticipants (n=66), in addition to functional gains, identified an age-adjusted HR of 0.11 (SE, 1.07 [95% CI, 0.01 0.90]; P=0.039) for the effect of participant group, suggesting that nonparticipants had a 9 times higher hazard of mortality.844 6. Although acknowledging that educating patients with stroke or TIA about their condition and the causesoftheirstrokeisanimportantaspectofstroke care, evidence does not support its role in modifying health risk behaviors. The Cochrane review of inter- ventions for improving modifiable risk factor control in the secondary prevention of stroke identified that patient education alone does not lead to improve- ments in modifiable risk factor control or the pre- vention of recurrent cardiovascular events.829 The recent STANDFIRM trial (Shared Team Approach Between Nurses and Doctors for Improved Risk Factor Management for Stroke Patients; N=563) of specialist review and nurse education found no effect on attainment of cardiometabolic targets for Similarly, the ExStroke trial (N=314 ambulatory participants with stroke) identified that repeated encouragement with verbal instruction on being physically active over a 2-year period after stroke was not an effective means of increasing physical activity participation.129 Knowledge Gaps and Future Research Current knowledge gaps in this area include the following: The optimal behavior change intervention to reduce recurrent stroke is unknown at present, as is the optimal window to deliver interventions of this nature. Multiple systematic reviews of lifestyle-based behavioral interventions identify an existing knowl- edge gap relating to the potential of the inter- ventions reported to date to affect outcomes of recurrent stroke and other cardiovascular end points in the longer term, beyond the intervention Many behavioral interventions in published tri- als after stroke fail to identify whether a behavior change theory underpinned the intervention deliv- ered, making it difficult to ascertain successful and unsuccessful components of complex behavior A significant knowledge gap exists with respect to the specific or allied role of family caregivers and dyads in stroke secondary prevention in both the promotion and maintenance of health behaviors after stroke. To address these shortfalls, future prospective, multi- centered randomized controlled trials are required that consider and report the following: A clearly identified behavior change theory as a basis for intervention A documented time point after stroke for targeted intervention delivery A detailed intervention description that identifies the frequency and duration of the intervention, the personnel required to deliver the intervention, the intervention setting (eg, subacute care, commu- nity care, mixed), and the skill level and training in behavioral counseling of the interventionist Data collection that permits disaggregation by sex and other relevant characteristics to identify responders/nonresponders to intervention. 6.3. Health Equity Recommendations for Health Equity Referenced studies that support recommendations are summarized in online Data Supplement 65. COR LOE Recommendations In patients with stroke or TIA, evaluating and addressing social determinants of health (eg, literacy level, language proficiency, medica- tion affordability, food insecurity, housing, and transportation barriers) when managing stroke risk factors is recommended to reduce healthcare disparities. In patients with stroke or TIA, monitoring the achievement of nationally accepted, evidence- based performance measures is recommended to allow inequities to be identified and addressed. In patients with stroke or TIA, systematic adoption of the Agency for Healthcare Research and Quality Universal Precautions Toolkit for Health Literacy is recommended to integrate health literacy into the secondary prevention of stroke. In patients from urban, predominantly minority, or low-socioeconomic-status groups with stroke or TIA, the optimal intervention model for improving stroke risk factor control and reducing disparities is unknown.815,856 859 Synopsis Certain populations have documented inequities in recurrent stroke risk and vascular risk factor control after stroke. Many of these inequities are caused and perpetuated by structural racism, defined as the normal- ization and legitimization of an array of dynamics (histori- cal, cultural, institutional and interpersonal) that routinely advantage White people while producing cumulative and chronic adverse outcomes for people of color. 860,861 Non- White populations have higher recurrent stroke risk,862,863 are less likely to receive guideline-recommended sec- ondary stroke prevention interventions,864 and have poorer risk factor control after stroke.10,13,819,865,866 Other populations at risk for inequities in risk factor control after stroke include women, rural dwellers, the elderly, immigrants, individuals with low socioeconomic status, and lesbian, gay, bisexual, transgender, and queer or Although standardizing CLINICAL STATEMENTS AND GUIDELINES Kleindorfer care and increasing the consistency of care have been shown to reduce race/ethnic inequities in care,874 special approaches may be required to actively reduce recur- rent stroke risk in populations at risk for inequities and to address the underlying structural determinants of ineq- uities. Several RCTs have tested secondary stroke pre- vention interventions in predominantly Black, Hispanic, and low-socioeconomic-status populations.815,856 859 The optimal approaches for reducing recurrent stroke risk in high-risk populations are unclear; however, key strate- gies include evaluating and addressing social determi- nants of health, implementing evidence-based protocols, monitoring adherence to evidence-based guidelines on a population level, enhancing health and stroke literacy and self-management skills, and using the Agency for Healthcare Research and Quality Universal Precautions Toolkit of Health Literacy. Recommendation-Specific Supportive Text 1. Socioeconomic inequalities are strong predictors of Interventions should be tailored to patients socioeconomic and educational status, as well as cultural, work, and home environments.19,875 Examples of upstream social determinants of health that affect treatment adherence and ASCVD health outcomes include comorbid mental illness, lack of health literacy, exposure to adversity (eg, home/com- munity violence, trauma exposures, safety concerns), financial strain, inadequate housing conditions, lack of food security (ie, access to affordable and nutritious food), structural and individual discrimination, and inad- equate social support.876 The Centers for Medicare & Medicaid Services has developed a screening tool to assess 5 domains of non health-related measures that affect health outcomes: housing instability, food insecurity, transportation difficulties, utility assistance needs, and interpersonal safety.877 and Stroke convened an expert panel to provide rec- ommendations on key priorities for health disparities research in stroke. One recommendation was to use population-based surveillance to assess achievement of evidence-based guidelines.878 Alliances with the federal government through the National Institute of Neurological Disease and Stroke, Centers for Disease Control and Prevention, nonprofit organiza- tions such as the AHA/ASA, and medical specialty groups such as the American Academy of Neurology and the Brain Attack Coalition are needed to coor- dinate, develop, and optimize implementation of evi- dence-based stroke prevention recommendations.9 3. The AHRQ Universal Precautions Toolkit for Health is a publicly available document that includes a 21-step approach to ensuring that writ- ten and oral instructions to patients are clear, under- standable, and sensitive to health literacy. Healthcare providers who listen, speak slowly, use nonmedical language, encourage questions, apply teach-back methods, address language differences, are culturally competent, and incorporate graphics in their teach- ing promote a culture sensitive to health literacy.880 4. Several RCTs have tested secondary stroke pre- vention interventions in predominantly Black, Hispanic, and/or low-socioeconomic-status pop- In all trials, primary outcomes improved in the intervention and control groups without significant differences between the 2 arms. A few of the trials showed improvement in second- ary outcomes or subpopulations. The SUSTAIN trial (Systemic Use of Stroke Averting Interventions) of a culturally tailored Chronic Care Model based inter- vention (incorporating advance practice provider delivery of evidence-based care, protocols, real- time decision support, self-management support, and education) in a multiracial/multiethnic popula- tion in a safety-net setting showed better LDL con- trol (secondary outcome) in the intervention arm; intervention participants were more likely to lower LDL <100 md/dL compared with control subjects In the PRAISE trial (Prevent Recurrence of All Inner-City Strokes Through Education) of peer-led community-based poststroke self-management workshops in the inner city, the primary composite outcome of BP, LDL, and antithrombotic use at 6 months was not different in the intervention and control arms, but a higher proportion of those randomized to the inter- vention had controlled BP at 6 months (76% ver- Finally, a subgroup analysis of Hispanic individuals enrolled in the DESERVE trial (Discharge Educational Strategies for Reduction of Vascular Events), evaluating the efficacy of a cul- turally tailored skills-based intervention, revealed a 9.9 mmHg greater reduction in SBP compared Knowledge Gaps and Future Research Numerous RCTs of culturally tailored complex secondary stroke prevention interventions in populations at high risk for inequities have failed to show a clear improvement in primary outcomes compared with usual care. Further research is needed to determine optimal strategies for reducing inequities in risk factor control after stroke. Key populations at risk for inequities include those from Black, Hispanic, and indigenous backgrounds; women; the elderly; immigrants; lesbian, gay, bisexual, transgen- der, and queer or questioning individuals; and those with low income, low educational attainment, limited English proficiency, unstable housing, inadequate social sup- port, concurrent substance abuse, comorbid psychiatric illness, or history of incarceration. Although epidemio- logical studies have elucidated race/ethnicity , age-, and sex-specific disparities in risk factor control after stroke, less is known about risk factor control among other CLINICAL STATEMENTS AND GUIDELINES Kleindorfer vulnerable populations at risk for inequities. Specific gaps and areas for future research include the following: A more thorough understanding of which populations have inequities in risk factor control after stroke. A more nuanced understanding of the drivers of inequities in risk factor control after stroke, including social determinants of health and structural racism. Strategies for improving risk factor control among groups at risk for inequities. Strategies for addressing social determinants of health among stroke survivors. AHA STROKE COUNCIL SCIENTIFIC STATEMENT OVERSIGHT COMMITTEE Joseph P. Broderick, MD, FAHA, Chair; Jose Romano, MD, FAHA, Vice Chair; Sepideh Amin-Hanjani, MD, FAHA, Immediate Past Chair; Terrie Black, DNP, FAHA*; Joan Breen, MD; Cheryl Bushnell, MD, FAHA; Mandip Dhamoon, MD, DPh, FAHA; Justin Fraser, MD, FAHA; Karen L. Furie, MD, MPH, FAHA*; Philip B. Gorelick, MD, MPH, FAHA; Kama Guluma, MD; Richard Harvey, MD, FAHA; George Howard, DPH, FAHA; Walter N. Kernan, MD; Charles Kircher, MD, FAHA; Nerissa Ko, MD; William Mack, MD, FAHA ; Jason Mackey, MD, FAHA*; Norma McNair, RN, MSN, PhD, FAHA; Peter Panagos, MD, BA, FAHA; Kevin N. Sheth, MD, FAHA ; Gregory Zipfel, MD, FAHA* PRESIDENT AND STAFF American Heart Association/American Stroke Association Mitchell S. V. Elkind, MD, MS, FAAN, FAHA, President Nancy Brown, Chief Executive Officer MariellJessup,MD,FAHA,ChiefScienceandMedicalOfficer Radhika Rajgopal Singh, PhD, Senior Vice President, Office of Science and Medicine Jody Hundley, Production and Operations Manager, Sci- entific Publications, Office of Science Operations AHA/ASA Stroke Guidelines Staff Prashant Nedungadi, PhD, Director, Stroke Guidelines, Office of Science, Medicine and Health Melanie Stephens-Lyman, MS, Guideline Advisor, Stroke, Office of Science, Medicine and Health Anne Leonard, MPH, RN, FAHA, CCRC, Senior Science and Medicine Advisor, Office of Science, Medicine and Health Katherine Sheehan, PhD, Evidence Review Committee Staff Lead, Science and Medicine Advisor, Office of Science, Medicine and Health ARTICLE INFORMATION The American Heart Association makes every effort to avoid any actual or poten- tial conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Spe- cifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This guideline was approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee on January 19, 2021, and the American Heart Association Executive Committee on April 12, 2021. A copy of the document is available at https://professional.heart.org/statements by using either Search for Guidelines & Statements or the Browse by Topic area. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@ wolterskluwer.com. Supplemental materials are available with this article at https://www.ahajournals. org/doi/suppl/10.1161/STR.0000000000000375. The American Heart Association requests that this document be cited as follows: Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Associa- tion/American Stroke Association. Stroke. 2021;52:e364 e467. doi: 10.1161/ The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Se- lect the Guidelines & Statements drop-down menu, then click Publication Development. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the Copyright Permissions Re- quest Form appears in the second paragraph (https://www.heart.org/en/about- us/statements-and-policies/copyright-request-form). *Former Stroke Scientific Statement Oversight Committee Member, current member during the writing effort. AANS/CNS Liaison. AAN Liaison. CLINICAL STATEMENTS AND GUIDELINES Kleindorfer Appendix 1. Writing Group Relationships With Industry and Other Entities (Relevant): 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack Writing group member Employment Research grant Other research support Speakers bureau/ honoraria Expert witness Ownership interest Consultant/ advisory board Other Dawn O. Kleindorfer University of Michigan NIH (epidemiology of stroke) None None None None None None Amytis Towfighi University of Southern California NIH/NINDS (secondary stroke prevention trial) None None None None None None Seemant Chaturvedi School of Medi- cine, University of Maryland Boehringer-Ingelheim (grant support)* None None None None None NINDS (executive committee Kevin M. Cockroft (AANS/CNS WG Represen- tative) Penn State Hershey Medical Center Medtronic (PI for multi-institution study) ; Nico Corp (PI for multi-institu- tion study) Intersocietal Accreditation Commission (Board of Directors)* None None Actuated Medical* Medtronic ; Minnetronix* None Jose Gutierrez Columbia University Medical Center NIH (PI in research grant) None None Hanna, Campbell & Powell, LLP*; Heidell, Pittoni, Murphy & Bach, LLP*; Aaronson Rappaport*; Johnson, Graffe, Keay, Moniz & Wick*; Luca Law, PLLC* None None None Hooman Kamel Weill Cornell Medical College BMS (BMS provides in-kind study drug [apixaban/aspirin/placebo] for ARCADIA trial, of which he is co-PI) ; Boehringer Ingelheim (Endpoint Adjudication Committee for a trial of empagliflozin) ; Medtronic (unpaid Steering Committee member of STROKE AF Trial)*; NIH/ NINDS (co-PI of ARCADIA trial, PI of LANTERN observational study of atrial cardiopathy and racial disparities in stroke, coinvestigator of a stroke policy simula- tion model project) ; Roche Diagnostics (Roche Diagnostics provides in-kind study assay kits [NT-proBNP] for ARCADIA trial, of which he is co-PI) ; Clinical Endpoint Adjudication Committee for an RCT related to empagliflozin, a diabetes drug. The trial sponsor is Boehringer- Ingelheim. I am contracted to do this through Quintiles None None None None None None Walter N. Kernan Yale School of Medicine None None None None None None None Steven J. Kittner Veterans Affairs Maryland Health Care System; University of Maryland School of Medicine R01NS100178 (analysis grant of SiGN, an established ischemic stroke genetics consortium) ; R01NS105150 (establishes a new consortium for the study of the genetics of early-onset ischemic stroke) ; 2U01NS036695- 15A1 (genetic and environmental risk factors for hemorrhagic stroke) ; automated pipeline for extracting MRI brain imaging phenotypes and mapping genes associated with varia- tion in these traits)*; Regeneron (no personal research support at present but discussing joint research involving exome sequencing of ischemic strokes in young adults internationally)* None None None None None None (Continued) Disclosures CLINICAL STATEMENTS AND GUIDELINES Kleindorfer Enrique C. Leira University of Iowa, Hospitals and Clinics NIH/NINDS salary support through U24 and R21 grant mechanisms) ; Keystone Heart (performed local neurological assessments as a local co-PI in a cardiology trial)*; Edwards Lifesciences (performed local neurological assess- ments as a local co-PI in a cardiology trial)*; Bayer AG and Jansen LLC (was the local PI for the NAVIGATE-ESUS trial)*; ZZ Biotech (consulting in the RHAPSODY acute trial proposal that will be submitted to NIH)*; NIH-Fred Hutchinson Research Center (adjudicate stroke events for the WHI NIH Study)* None None None None None None Olive Lennon University College Dublin, School of Public Health, Phys- iotherapy and Sports Science, Health Sciences Centre (Ireland) EU MSCA (research exchange pro- gramme grant)*; UCD (seed funding dissemination grant)* None None None Cft Recruit- ment Ltd registration Cft Recruit- ment Ltd registration (immedi- ate family members) None None Debbie Lombardi-Hill (patient representative) Self-employed Vanderbilt University Medical Center (consultant to a PCORI-funded Com- parative Effectiveness Trial for Stroke Post-Acute Care)* None None None Lombardi Hill Consult- ing Group, LLP ; Stroke Challenges, LLC* None Lombardi Hill Consulting Group, LLP (owner/ principal) ; Stroke Chal- lenges, LLC (cofounder/ co-owner)* James F. Meschia Mayo Clinic NINDS (Crest-2 Trial; he is one of 3 co-PIs for this trial that compares revascularization with and without intensive medical management. The trial is funded by NINDS. His support is funding for salary substitution to devote 30% of his effort to the trial) None None None None None None Thanh N. Nguyen Boston Medical Center Medtronic (PI Clear Study)* None None None None None None Peter M. Pollak Mayo Clinic None None None None None None None Pasquale Santangeli Hospital of the University of Pennsylvania None None Abbott Medical*; Biosense Webster*; Biotronik*; Medtronic* None None Abbott Medi- cal*; Baylis Medical*; Biosense Webster* None Anjail Z. Sharrief University of Texas Medical School at Houston None Omron (donation of blood pressure machines for clinical care and research)* None None None None None Sidney C. Smith Jr University of North Carolina None None None None None None None Tanya N. Turan (AAN WG Representa- tive) Medical Univer- sity of South Carolina Sanofi-Regeneron (alirocumab is donated to the CREST2, for which she is the director of medical management) None None None None Boehringer Ingelheim*; Gore*; Pfizer None Linda S. Wil- liams Roudebush VA Medical Center VHA (VA HSR&D PI) None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (a) the person receives $5000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Appendix 1. Continued Writing group member Employment Research grant Other research support Speakers bureau/ honoraria Expert witness Ownership interest Consultant/ advisory board Other CLINICAL STATEMENTS AND GUIDELINES Kleindorfer Appendix 2. Peer Reviewer Relationships With Industry and Other Entities (Comprehensive): 2021 Guideline for the Preven- tion of Stroke in Patients With Stroke and Transient Ischemic Attack Peer reviewer Employment Research grant Other research support Speakers bureau/ honoraria Expert witness Ownership interest Consultant/advisory board Other Mary Amatangelo Massaschusetts General None None None None None None None Hugo Aparicio Boston University School of Medicine American Academy of Neurol- ogy Career Development Award Alzheimer s Association Research grant None None None None None Negar Asdaghi University of Miami None None None None None None None Devin Brown University of Michi- gan NIH None Grand Rounds Honorarium The Ohio State University* None None None AHA* Askiel Bruno Medical College of Georgia at Augusta University NINDS ; Georgia Rehabilitation Foundation None Abbott Pharma* None None None None Cheryl Bushnell Wake Forest Baptist Health None None None None Care Directions, LLC* ZZ Biotech, Clinical Advisory Committee for RHAPSODY II trial* None Dominique Cadilhac Monash University Amgen (paid to Institution) None None None None None Med- tronic (donation paid to Institu- tion)* Clay Cauthen University of Texas None None Novartis* None None None None Tiffany Chen University of Penn- sylvania None None None None None None None Ephraim Church Penn State Health None None None None None None None John Cole University of Mary- land NIH/NINDS None None None None None None Gioacchino Curiale Boston University Neurology Associ- ates None None None National Medical Consultants PC* None None None Mary Cushman None None None None None None None None Alexandra Czap McGoven Medical School, University of Texas NIH None None None None None None Colin Derdeyn University of Iowa None None None None None None None Marco R. Di Tullio Columbia University NIH/NINDS None None None None None None Kenneth Gaines Vanderbilt University Medical Center National PI ; USDA Distance Learning and Telemedicine Grant None None Expert witness for medical malpractice* Stroke Link Health None None (Continued) CLINICAL STATEMENTS AND GUIDELINES Kleindorfer Philip B. Gorelick Michigan State Local Site PI for C3FIT recurrent stroke prevention trial funded by PCORI None None None None None Bayer*; Novartis* Virginia Howard University of Alabama at Birmingham NIH None None None None None None Judy Huang Johns Hopkins University None None None Weber Gal- lagher* Longeviti* None None Silvio Inzuccchi Yale School of Medicine None None None None None Boehringer Ingelheim*; AstraZeneca ; Novo Nordisk ; Merck* None Ashutosh Jadhav Barrow Brain and Spine Institute None None None None None None None Salomeh Keyhani University of Califor- nia, San Francisco None None None None None None None Anthony Kim University of Califor- nia San Francisco SanBio None None Consultant* None None None Christopher Kramer University of Virginia Regeneron None None None None None None Sandeep Kumar Beth Israel Deacon- ess Medical Center; Harvard Medical School NIH/NINDS None None None None None None Lester Y. Leung Tufts Medical Center NIH None None None None None None Helmi Lutsep Oregon Health & Science University None None None None None BMS*; Axiomatic SSP trial*; Coherex Medical Physician Advisory Board for Wavecrest*; NINDS/ Mayo Stroke Adjudi- cation Committee for Neurology* Modest* Alice Ma Royal North Shore Hospital None None None None None None None Prachi Mehndiratta University of Mary- land None None None None None None None J. Mocco Mount Sinai Health System Microvention ; Penumbra ; Stryker None None None BlinkTBI ; Cere- brotech ; Corin- dus ; Echovate ; Endostream ; Imperative Care ; Medtronic ; NTI ; Rebound Thera- peutics ; RIST ; Serenity ; Spi- naker ; Synchron ; Truvic ; Vastrax Cerebrotech ; Corin- dus ; Endostream ; Imperative Care ; Rebound Therapeu- tics ; Synchron ; Vastrax ; Viseon DePuy Synthes (F&B)* Sara Partington University of Pennsylvania None None None None None None None Aman Patel Massachusetts General Hospital Siemens None None None None Microvention ; Medtronic*; Penumbra* None Sabrina Phillips Mayo Clinic None None None None None None None Aleksandra Pikula University of Toronto Canadian Insti- tute of Health Research* Canadian Stroke Consortium* None None None None None Appendix 2. Continued Peer reviewer Employment Research grant Other research support Speakers bureau/ honoraria Expert witness Ownership interest Consultant/advisory board Other (Continued) CLINICAL STATEMENTS AND GUIDELINES Kleindorfer Raymond Reichwein Penn State Health Athersys None None None None None None Gustavo Rodriguez Texas Tech School of Medicine None None None None None None None Christianne Roumie VA Tennessee Valley Healthcare System; Vanderbilt University VA ; CSRD ; NIH/NHLBI ; AHRQ ; PCORI None None None None None None Julie Shulman Boston University Medical Center NIH None None None None None None Jason Sico Yale University VA None None None None None None James Siegler Cooper University Hospital None None None None None Ceribell None Brian Silver University of Mas- sachusetts Medical School None None None Law firms for expert review None Women s Health Initiative review and committee work*; Best Doctors, Inc. case reviews* Hono- raria for reviews for Ebix, MedLink, Med- scape* Eric Smith University of Cal- gary Canadian Insti- tutes of Health Research ; Brain Canada University of Ottawa Heart Institute ; McMaster University None None None Bayer*; Biogen*; Cyclerion*; Javelin* UpTo- Date* Farzaneh Sorond Feinberg School of Medicine Northwest- ern University None None None None None None None Barney Stern Johns Hopkins University None None None None None None None Jeffrey Switzer Augusta University None None None None None None None Stavropoula Tjoumakaris Thomas Jefferson University None None None None None None None Stanley Tuhrim Mount Sinai Hospital None None None None None None None David Wang Barrow Neurological Institute None None Boehringer Ingelheim* None None None None Babu Welch University of Texas Southwestern Medi- cal Center None None Stryker Neuro- vascular* None None Medtronic; Microven- tion*; Stryker Neuro- vascular* Peter Lazic* Deborah J. Wexler Massachusetts Hospital and Harvard Medical School NIDDK None None None None None Novo Nordisk* Daniel Woo University of Cincinnati NIH None None None None None None Bradford Worrall American Academy of Neurology NIH None None None None None None Henry Klar Yaggi Yale School of Medicine None None None None None None None Richard Zweifler Tulane University None None None None None None None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Ques- tionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (a) the person receives $5000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $5000 or more of the fair market value of the entity. 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