Vertebrobasilar dolicho- ectasia is associated with traditional ischemic stroke risk factors such as increasing age, hypertension, and male sex. However, its relationship to atherosclerotic disease is less clear.765 767 Although many patients may be asymptomatic, others may present with a variety of CLINICAL STATEMENTS AND GUIDELINES Kleindorfer clinical syndromes, including cranial nerve or brainstem compression, obstructive hydrocephalus, subarachnoid hemorrhage, and ischemia.760,764,768 Ischemic events may be related to thromboembolic phenomenon but may also result from the disruption of small perforat- Asymptomatic patients have the most whereas those presenting with compressive symptoms or demonstrating progressive enlargement have a worse prognosis.760,768,770 The rate of recurrent ischemic stroke may be quite high,761,771,772 with 1 study reporting a rate of 19% at just under 2 Increasing basilar artery diameter, diffuse intracranial dolichoectasia, and associated ischemic heart disease increased the risk of recurrent events.761 Many patients with vertebrobasilar dolichoectasia are treated medically with antithrombotic medication, but high-quality evidence on the management strategies for patients with vertebrobasilar dolichoectasia, par- ticularly in the setting of a prior ischemic stroke or TIA, is lacking. Several case series describe endovas- and various surgical interven- ; however, there is little evidence that such treatments reduce the risk of additional ischemic events in patients who present with an ischemic stroke or TIA. The literature on dolichoectasia of the anterior circulation in patients with prior ischemic stroke or TIA is even more sparse; therefore, this topic is not addressed in this guideline. Recommendation-Specific Supportive Text 1. There are no prospective RCTs comparing anti- thrombotic therapies with observation alone. However, case series tend to suggest that anti- thrombotic therapy lowers the risk of recurrent ischemic events compared with the natural his- There are also no prospective RCTs comparing antiplatelet strategies (either aspirin or second-generation antiplatelet drugs) with anticoagulation.


However, case series tend to suggest that anti- thrombotic therapy lowers the risk of recurrent ischemic events compared with the natural his- There are also no prospective RCTs comparing antiplatelet strategies (either aspirin or second-generation antiplatelet drugs) with anticoagulation. The case series reviewed dem- onstrated no clear or consistent benefit for 1 form of antithrombotic therapy over another.760 763 Although 1 small case series favored anticoagu- lation, not all of the patients in that series pre- sented with ischemic symptoms, and the series consisted of patients with fusiform aneurysms rather than true vertebrobasilar dolichoecta- Although the risks of hemorrhage appear to be low in patients presenting with ischemic there are insufficient data to pro- vide a recommendation for anticoagulation over antiplatelet therapy. Knowledge Gaps and Future Research Many important issues about the management of patients with vertebrobasilar dolichoectasia remain unclear. Some of these include the following: Development of an agreed-on definition for ver- tebrobasilar dolichoectasia that is distinguishable from the definition of a fusiform aneurysm. Accumulation of more robust natural history data with detailed clinical outcomes. Clarification of the type, dosing regimens, and efficacy of antiplatelet therapy versus anticoagu- lation for primary and secondary ischemic stroke prevention. Improved understanding of the role of reconstruc- tive procedures, whether endovascular or open surgical, in the management of patients with verte- brobasilar dolichoectasia. 5.18. Embolic Stroke of Undetermined Source Recommendations for ESUS Referenced studies that support recommendations are summarized in online Data Supplement 56. COR LOE Recommendations Benefit B-R In patients with ESUS, treatment with direct oral anticoagulants is not recommended to reduce risk of secondary stroke.779,780 Benefit B-NR In patients with ESUS, treatment with ticagre- lor is not recommended to reduce the risk of Synopsis ESUS is an evolving stroke subtype commonly defined as a nonlacunar cryptogenic ischemic stroke.


COR LOE Recommendations Benefit B-R In patients with ESUS, treatment with direct oral anticoagulants is not recommended to reduce risk of secondary stroke.779,780 Benefit B-NR In patients with ESUS, treatment with ticagre- lor is not recommended to reduce the risk of Synopsis ESUS is an evolving stroke subtype commonly defined as a nonlacunar cryptogenic ischemic stroke. Lack of a standard definition has complicated studies of ESUS, with 1 review finding that many studies use variable diagnostic criteria, including type and duration of car- diac rhythm monitoring.782 This complexity in defining ESUS is one of the reasons proposed for the nega- tive clinical trials of anticoagulation compared with antiplatelet medication for stroke prevention779,780 and fuels much of the ongoing research to further define the association between markers of atrial cardiopathy and methods of assessing cardiac rhythm disorders and risk of recurrent stroke. Subgroup analyses of the NAVIGATE ESUS study (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Sys- temic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) suggest that patients with left atrial diameter >4.6 cm may benefit from anticoagula- but those with PFO did not.784 A post hoc analysis of patients with ESUS enrolled in the SOCRATES trial (Soluble Guanylate Cyclase Stimulator in Heart Failure Studies) did not find an association between ticagrelor treatment and reduced vascular event risk.781 Ongoing randomized trials that may provide additional informa- tion about the efficacy of treatments to prevent recur- rent stroke among patients with ESUS include studies using prolonged rhythm monitoring to identify patients, studies that select patients with various markers of and trials that include MRI-defined CLINICAL STATEMENTS AND GUIDELINES Kleindorfer new ischemic events (silent strokes) as clinical trial Recommendation-Specific Supportive Text 1.


Subgroup analyses of the NAVIGATE ESUS study (Rivaroxaban Versus Aspirin in Secondary Prevention of Stroke and Prevention of Sys- temic Embolism in Patients With Recent Embolic Stroke of Undetermined Source) suggest that patients with left atrial diameter >4.6 cm may benefit from anticoagula- but those with PFO did not.784 A post hoc analysis of patients with ESUS enrolled in the SOCRATES trial (Soluble Guanylate Cyclase Stimulator in Heart Failure Studies) did not find an association between ticagrelor treatment and reduced vascular event risk.781 Ongoing randomized trials that may provide additional informa- tion about the efficacy of treatments to prevent recur- rent stroke among patients with ESUS include studies using prolonged rhythm monitoring to identify patients, studies that select patients with various markers of and trials that include MRI-defined CLINICAL STATEMENTS AND GUIDELINES Kleindorfer new ischemic events (silent strokes) as clinical trial Recommendation-Specific Supportive Text 1. The NAVIGATE ESUS and RESPECT ESUS (Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source) randomized trials found no reduction in secondary stroke risk among patients with ischemic stroke or TIA who were treated with a direct oral anticoagulant.779,780 2. A post hoc subgroup analysis of subjects with ESUS enrolled in the SOCRATES trial (4329 subjects, 32.8%) found no treatment effect by ESUS category of ticagrelor on recurrent vascu- lar event risk.781 Knowledge Gaps and Future Research Although ongoing trials may help address some of the questions about ESUS, knowledge gaps persist related to the definition of ESUS and optimal treatment for sec- ondary stroke prevention: What markers of atrial dysfunction are most strongly associated with recurrent stroke risk? Are there clinical factors that help identify patients with ESUS who may benefit from anticoagulation rather than antiplatelet treatment for secondary prevention?


Are there clinical factors that help identify patients with ESUS who may benefit from anticoagulation rather than antiplatelet treatment for secondary prevention? One of the primary challenges in identifying treat- ments to reduce the risk of second stroke in patients with ESUS is the difficulty of clearly defining criteria for ESUS diagnosis. Future trials should address these topics: The use of different strategies for long-term arrhyth- mia detection and their impact on ESUS diagnosis criteria. The use of additional cardiac markers of atrial pathology, including atrial size, and their impact on ESUS diagnosis criteria, secondary stroke risk, and response to anticoagulation. 5.19. Use of Antithrombotic Medications in Secondary Stroke Prevention As described in prior sections of this guideline, recom- mendations for secondary stroke prevention have been constructed on the basis of the best evidence among patients with a specific cause of their initial ischemic stroke. For patients with noncardioembolic ischemic stroke who do not have a specific identified cause, ques- tions about optimal antithrombotic medication use for secondary prevention may thus arise. In general, when those specific antithrombotic recommendations vary slightly from the general recommendations that follow in this section, the most specific recommendation should be prioritized. Recommendations for Antithrombotic Medications Referenced studies that support recommendations are summarized in online Data Supplements 57 59. COR LOE Recommendations In patients with noncardioembolic ischemic stroke or TIA, antiplatelet therapy is indicated in preference to oral anticoagulation to reduce the risk of recurrent ischemic stroke and other cardiovascular events while minimizing the risk For patients with noncardioembolic ischemic stroke or TIA, aspirin 50 to 325 mg daily, clopidogrel 75 mg, or the combination of aspi- rin 25 mg and extended-release dipyridamole 200 mg twice daily is indicated for secondary prevention of ischemic stroke.


COR LOE Recommendations In patients with noncardioembolic ischemic stroke or TIA, antiplatelet therapy is indicated in preference to oral anticoagulation to reduce the risk of recurrent ischemic stroke and other cardiovascular events while minimizing the risk For patients with noncardioembolic ischemic stroke or TIA, aspirin 50 to 325 mg daily, clopidogrel 75 mg, or the combination of aspi- rin 25 mg and extended-release dipyridamole 200 mg twice daily is indicated for secondary prevention of ischemic stroke.*791 794 For patients with recent minor (NIHSS score 3) noncardioembolic ischemic stroke or high-risk TIA (ABCD2 score 4), DAPT (aspirin plus clopidogrel) should be initiated early (ideally within 12 24 hours of symptom onset and at least within 7 days of onset) and continued for 21 to 90 days, followed by SAPT, to reduce the risk of recurrent ischemic For patients with recent (< 24 hours) minor to moderate stroke (NIHSS score 5), high-risk score 6), or symptomatic intra- cranial or extracranial 30% stenosis of an artery that could account for the event, DAPT with ticagrelor plus aspirin for 30 days may be considered to reduce the risk of 30-day recur- rent stroke but may also increase the risk of serious bleeding events, including ICH.797 For patients already taking aspirin at the time of noncardioembolic ischemic stroke or TIA, the effectiveness of increasing the dose of aspirin or changing to another antiplatelet medication is not well established.410,798 800 3: Harm ASR For patients with noncardioembolic ischemic stroke or TIA, the continuous use of DAPT (aspirin plus clopidogrel) for >90 days or the use of triple antiplatelet therapy is associated with excess risk of hemorrhage.381,382,801 SR indicates systematic review.


*791 794 For patients with recent minor (NIHSS score 3) noncardioembolic ischemic stroke or high-risk TIA (ABCD2 score 4), DAPT (aspirin plus clopidogrel) should be initiated early (ideally within 12 24 hours of symptom onset and at least within 7 days of onset) and continued for 21 to 90 days, followed by SAPT, to reduce the risk of recurrent ischemic For patients with recent (< 24 hours) minor to moderate stroke (NIHSS score 5), high-risk score 6), or symptomatic intra- cranial or extracranial 30% stenosis of an artery that could account for the event, DAPT with ticagrelor plus aspirin for 30 days may be considered to reduce the risk of 30-day recur- rent stroke but may also increase the risk of serious bleeding events, including ICH.797 For patients already taking aspirin at the time of noncardioembolic ischemic stroke or TIA, the effectiveness of increasing the dose of aspirin or changing to another antiplatelet medication is not well established.410,798 800 3: Harm ASR For patients with noncardioembolic ischemic stroke or TIA, the continuous use of DAPT (aspirin plus clopidogrel) for >90 days or the use of triple antiplatelet therapy is associated with excess risk of hemorrhage.381,382,801 SR indicates systematic review. *The subgroup of patients with noncardioembolic stroke who meet clinical cri- teria for DAPT have a more specific recommendation for antiplatelet therapy as described in Recommendation 3. Synopsis Patients with stroke/TIA not attributable to other stroke causes related to specific antithrombotic rec- ommendations (eg, AF, intracranial stenosis) should receive antithrombotic therapy for the prevention of recurrent stroke.


Synopsis Patients with stroke/TIA not attributable to other stroke causes related to specific antithrombotic rec- ommendations (eg, AF, intracranial stenosis) should receive antithrombotic therapy for the prevention of recurrent stroke. If patients with mild stroke or high- risk TIA are evaluated early after the onset of their stroke, starting short-term DAPT followed by long-term SAPT is preferred compared with SAPT according to the reduction of risk of early recurrent stroke.384,410 Beyond 90 days after stroke, DAPT is associated with increased risk of bleeding and no benefit in long-term reduction of recurrent stroke risk.381,382 For patients not treated until later after their stroke event, use of any SAPT is indicated to reduce long-term recurrent CLINICAL STATEMENTS AND GUIDELINES Kleindorfer stroke risk. Although the optimal time to switch from DAPT to SAPT to maximize benefit and reduce risk is not entirely clear, benefit in stroke reduction with DAPT may be maximized as early as the first 21 days after the event.802 This treatment approach is summa- rized in Figure 6, with consideration of clinical event criteria, DAPT versus SAPT, and length of therapy. Tri- ple therapy with aspirin, clopidogrel, and dipyridamole and use of anticoagulation in this population are not recommended on the basis of increased bleeding risk and no benefit in stroke reduction.790,801 Recommendation-Specific Supportive Text 1. The WARSS study randomized 2206 patients with stroke not attributable to cardioembolism or high- grade carotid stenosis to adjusted-dose warfarin The pri- mary end point of 2-year recurrent ischemic stroke or death was no different between the 2 groups (17.8% warfarin versus 16% acetylsalicylic acid; HR, 1.13 [95% CI, 0.92 1.38]).


The WARSS study randomized 2206 patients with stroke not attributable to cardioembolism or high- grade carotid stenosis to adjusted-dose warfarin The pri- mary end point of 2-year recurrent ischemic stroke or death was no different between the 2 groups (17.8% warfarin versus 16% acetylsalicylic acid; HR, 1.13 [95% CI, 0.92 1.38]). Similarly, a sub- sequent meta-analysis of 8 other trials of VKA among 5762 patients with TIA or nondisabling noncardioembolic stroke found no benefit in sec- ondary stroke prevention with the use of oral anti- coagulation of various intensities compared with antiplatelet agents (medium-intensity anticoagula- both medium-intensity anticoagulation and high- intensity anticoagulation were associated with a significantly increased risk of bleeding.789 2. A series of single antiplatelet trials conducted in patients with noncardioembolic stroke did not use clinical eligibility criteria in the same man- ner as the more recent DAPT trials. Thus, some patients in the general noncardioembolic stroke pathogenesis group may qualify for the more Figure 6. Antiplatelet therapy for noncardioembolic stroke and transient ischemic attack (TIA). Note: Algorithm does not apply to patients who receive acute thrombolysis. Note: Please see Section 5.1.1 for recommendations related to severe symptomatic intracranial large vessel stenosis. Early ischemic stroke (IS), <24 hours from onset; high-risk TIA, ABCD2 score 4; low-risk TIA, score <4; dual antiplatelet, acetylsalicylic acid (ASA)+clopidogrel. Colors correspond to Class of Recommendation in Table 3. NIHSS indicates National Institutes of Health Stroke Scale. Data from Brown et al,15 Pan et al,409 and Wang et al.410 CLINICAL STATEMENTS AND GUIDELINES Kleindorfer specific recommendation for early DAPT. For those who do not meet DAPT clinical criteria, SAPT is recommended.


For those who do not meet DAPT clinical criteria, SAPT is recommended. The PRoFESS trial found no dif- ference in secondary stroke prevention after noncardioembolic stroke for aspirin-dipyridamole The ESPRIT trial (European/ Australasian Stroke Prevention in Reversible suggested that aspirin-dipyri- damole may be slightly more effective than aspi- rin alone for vascular event prevention, as did the ESPS2 trial (Second European Stroke Prevention ESPS2 also showed that aspirin alone is more effective than placebo in reducing recur- rent stroke. The CAPRIE trial (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events) was not focused strictly on secondary prevention but found fewer events among patients treated with clopidogrel compared with those treated with aspirin, although no benefit was seen in stroke reduction among the stroke subgroup. A pooled analysis of trials in patients with lacunar stroke suggested that any of the evaluated antiplatelet agents were similarly effective compared with pla- Aspirin dosing may be guided by a recent patient-level pooled analysis of data from primary prevention RCTs that showed weight-based dos- ing (eg, aspirin 75 100 mg for patients weighing <70 kg and higher doses for those >70 kg) is more effective for the prevention of vascular events.803 However, similar studies have not been performed for secondary stroke prevention. 3. Recommendations for the short-term (21 90 days) use of DAPT with aspirin and clopidogrel are informed by 2 major RCTs,384,410 and a systematic review by an AHA Evidence Review Committee.15 Both the CHANCE and POINT trials compared DAPT with SAPT with aspirin initiated early after onset (<24 and <12 hours, respectively) of minor stroke (NIHSS score 3) or high-risk TIA (ABCD2 score 4) but varied in duration of DAPT treatment (21 and 90 days, respectively).


Recommendations for the short-term (21 90 days) use of DAPT with aspirin and clopidogrel are informed by 2 major RCTs,384,410 and a systematic review by an AHA Evidence Review Committee.15 Both the CHANCE and POINT trials compared DAPT with SAPT with aspirin initiated early after onset (<24 and <12 hours, respectively) of minor stroke (NIHSS score 3) or high-risk TIA (ABCD2 score 4) but varied in duration of DAPT treatment (21 and 90 days, respectively). DAPT dosing was also slightly differ- ent in the 2 trials: POINT used a 600-mg clopido- grel load (then 75 mg daily) and an aspirin regimen of 50 to 325 mg daily, whereas CHANCE used a 300-mg clopidogrel load (then 75 mg daily) and an aspirin load of 75 to 300 mg followed by 75 mg daily. Both trials demonstrated a reduction in recurrent ischemic stroke at 90 days. Further anal- yses of POINT revealed that the benefit of DAPT was seen primarily in the first 21 days.365 Meta- analyses that included other DAPT trials also have shown a reduction in recurrent stroke from DAPT compared with aspirin monotherapy, but the ben- efit is limited if not started early (<7 days) after the index event. Although most studies showed some increase in bleeding risk with DAPT, this was offset by the stroke prevention benefit if limited to short- 4.


Although most studies showed some increase in bleeding risk with DAPT, this was offset by the stroke prevention benefit if limited to short- 4. The use of ticagrelor (180-mg loading dose, then 90 mg twice daily) plus aspirin (300- to 325- mg loading does, then 75 100 mg daily) for 30 days was shown in the THALES trial to be slightly superior to aspirin alone in preventing recurrent stroke (recurrent stroke rate, 5% versus 6.3%; P=0.004) but was also associated with signifi- cantly increased risk of severe bleeding (0.5% ver- ICH was also significantly increased among the DAPT group (0.4% versus 0.1%; P=0.01), and significantly more patients in the DAPT group discontinued treatment because number needed to treat to prevent 1 primary out- come event was 92, and the number needed to harm was 263 for severe bleeding. Further study of this DAPT combination is needed to fully evaluate benefit and risk and to determine whether there is a specific subgroup most likely to benefit. The use of ticagrelor alone compared with aspirin was not associated with any reduction in cardiovascu- The use of ticagrelor plus aspirin for the subgroup of patients with ipsilateral carotid artery stenosis and intracranial stenosis is dis- cussed in Section 5.1.1, Intracranial Large Artery 5. No randomized trials have focused on the ques- tion of changing long-term antiplatelet therapy for the prevention of recurrent stroke. A meta-analysis suggested that, among the 4 studies that exam- ined stroke outcomes, there was a reduced risk of among patients who switched from 1 antiplatelet agent to another or to DAPT.800 However, both of the RCTs that specifically examined recur- rent stroke used DAPT rather than switching antiplatelets.


A meta-analysis suggested that, among the 4 studies that exam- ined stroke outcomes, there was a reduced risk of among patients who switched from 1 antiplatelet agent to another or to DAPT.800 However, both of the RCTs that specifically examined recur- rent stroke used DAPT rather than switching antiplatelets. In a subgroup analysis of the SPS3 trial, there was no benefit from the addition of clopidogrel to aspirin among patients with isch- emic stroke who were already taking aspirin (risk of recurrent stroke, 3.1% versus 3.3%; HR, 0.91 In a subgroup of patients already on aspirin in the CHANCE trial, there was a reduction in recurrent stroke among patients with clopidogrel added to aspirin versus aspirin alone A prospective registry study found that maintaining aspirin therapy was associated with higher recur- rent stroke rates (8.0%) compared with switching to another antiplatelet (6.9%) or adding another 6. Long-term use of DAPT with aspirin and clopi- dogrel has been shown in 2 secondary stroke CLINICAL STATEMENTS AND GUIDELINES Kleindorfer to have no benefit over SAPT for recurrent stroke prevention and to have a significantly increased risk of ICH and major bleeding. The exact duration of DAPT at which the risk of hemorrhage begins to outweigh the benefit of stroke prevention is unknown, but meta-analyses report as early as 21,802 or and those with more appear to be at higher risk of ICH with DAPT.


The exact duration of DAPT at which the risk of hemorrhage begins to outweigh the benefit of stroke prevention is unknown, but meta-analyses report as early as 21,802 or and those with more appear to be at higher risk of ICH with DAPT. Triple antiplatelet therapy with aspirin, clopidogrel, and dipyridamole was compared with standard antiplatelet therapy in the TARDIS trial (Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke), which found no difference in stroke outcomes and a significantly increased risk of bleeding with triple antiplatelet therapy.801 There may be other non stroke-related indica- tions for DAPT beyond 90 days after stroke (eg, recent drug-eluting cardiac stent placement), but these indications should be clarified to ensure that DAPT is not continued indefinitely beyond the clinically recommended time frame. Knowledge Gaps and Future Research To date, most DAPT trials have used aspirin and clopi- dogrel in combination for 21 to 90 days, but whether the duration of treatment should be 21 days, 90 days, or some other amount of time is not fully established. Similarly, whether other combinations of medications are equally or more beneficial is not known. The risk of DAPT among patients with stroke who may be more likely to experience hemorrhagic transformation of the ischemic stroke or other bleeding complication such as those with large stroke or microhemorrhages remains uncertain. Pharmacological responsiveness to antiplatelet ther- apy has been studied most extensively in patients with acute CVD, but the utility of such tests for guiding adjust- ment of antiplatelet medications for long-term prevention remains unclear. Relatively few head-to-head compari- sons of antiplatelet medications have been evaluated for the prevention of recurrent stroke, and in the existing trials, the benefit of 1 medication over another is small.


Relatively few head-to-head compari- sons of antiplatelet medications have been evaluated for the prevention of recurrent stroke, and in the existing trials, the benefit of 1 medication over another is small. Despite the common practice of changing antiplate- let medications in patients already taking 1 medication at the time of stroke, there is relatively little evidence from RCTs to support the benefit of this practice. 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.


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.


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.


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.


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.


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.


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.


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.


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.


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]).


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.


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.


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.


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.


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.


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, 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.


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.


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.


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.


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.


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.


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.


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.


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.


*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.


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.


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.


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.


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.


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