Prevention Of Recurrent Stroke Research Articles

Antiplatelet Therapy May Be Insufficient to Prevent Stroke Recurrence Before Percutaneous Patent Foramen Ovale Closure.

Antiplatelet Therapy May Be Insufficient to Prevent Stroke Recurrence Before Percutaneous Patent Foramen Ovale Closure.

Optimal extra-anatomical reconstructions of the carotid and vertebrobasilar basins (case reports)

The paper considers a case of surgical treatment of a patient with a completed stroke in the brain stem in anamnesis and with a clinical picture of chronic vertebrobasilar insufficiency caused by combined occlusion of the right vertebral artery (VA), hypoplasia of the left VA, and pathological tortuosity of the right internal carotid artery (ICA). The patient underwent extra-anatomical reconstructive surgery: simultaneous lowering of the loop of the right ICA and its resection in the middle third with redressement and reimplantation in the proximal third of the ICA with the formation of the ICA-ICA end-to-side anastomosis and the subsequent creation of an end-to-side anastomosis between the free end of the resected ICA and the V3 segment of the right VA. In addition, a case of surgical treatment of isolated bifurcation of the common carotid artery (CCA) that occurs when the proximal CCA is occluded and the blood flow is maintained in the external carotid artery (ECA) and ICA is considered. These reconstructive surgical interventions for combined lesions of the main arteries of the head are safe and reliable methods for the treatment of chronic cerebral ischemia and effective prevention of recurrent ischemic strokes.

Factors influencing recurrence after an ischemic stroke vary by sex

ABSTRACT Objectives To determine the factors that affect recurrent stroke after acute ischemic stroke, specifically between male and female groups. Methods We examined relative factors associated with recurrent stroke in Chinese patients with first-ever ischemic stroke. LASSO (least absolute shrinkage and selection operator) Cox regression were used to determine the predictors of recurrent stroke in the male and female groups. Next, We used Kaplan-Meier survival curves and interactions among these predictors to assess the association between relapse-related factors and recurrent stroke. Results During one year of follow-up, we documented 42 incidents of recurrent stroke in males and 15 in females. There was no significant difference in the overall recurrence rate between men and women. We finally identified three variables in males and one variable in females associated considerably with recurrent stroke by LASSO Cox regression. In females, good sleep appeared to be the most significant protective factor against recurrent stroke(hazard ratio [HR], 0.21; 95% CI, 0.08–0.57). In the male group, we found two risk factors: atherosclerotic burden (HR, 2.42; 95% CI, 1.30–4.51) and coronary heart disease (HR, 2.98; 95% CI, 1.16–7.66); and one protective factor: domestic/physical activities (HR, 0.45; 95% CI, 0.24–0.83). We also found an interaction between good sleep and domestic/physical activities in males (P interaction = 0.016). Discussion Our data indicate that the factors for recurrent stroke may differ by sex. Engaging in domestic/physical activities may substantially lower recurrent strokes in Chinese adult males. And good sleep in females appears to be more important in preventing stroke recurrence.

Younger Women’s Experiences of Stroke: A Qualitative Study

The incidence of stroke in younger adults is rising, especially among women. This study aims to explore the experiences of younger women who have had a stroke to understand their experience and support needs. This study used a qualitative description approach, recruiting eligible women through a snowball method. A focus group discussion was conducted to collect data, which was then analysed using thematic analysis. The five participants were 18 to 64 years old when they experienced their stroke and six to 18 years post-stroke when they participated in a focus group discussion in 2021. Four themes and 11 sub-themes emerged during the data analysis: 1) impacts of stroke (stroke onset and early experiences, physical and psychosocial effects, and changes to their roles and careers); 2) women’s reproductive health (pregnancy, on the contraceptive pill, and effect of anticoagulants on menstruation); 3) self-management (being a woman, healthcare monitoring, and self-care); and 4) support (internal and external support). The younger woman’s burden after stroke is complex due to their risk factors, symptoms, and recovery needs. Therefore, developing specific long-term rehabilitation strategies for younger women are needed for more effective stroke rehabilitation and recurrent stroke prevention. TE REO MĀORI TRANSLATION Ngā wheako o ngā wāhine taitamariki o te roro ikura: He rangahau whakaahua kounga Ngā Ariā Matua E piki haere ana te pānga o te roro ikura i waenga i ngā pakeke āhua taitamariki, otirā he tino pērā mō te wahine. E whai ana tēnei rangahau kia tūhuratia ngā wheako o ngā wāhine taitamariki kua pāngia e te roro ikura kia mārama kē atu ō rātou wheako me ō rātou hiahia tautoko. I whakamahia e tēnei rangahau tētahi ara whakamārama whakaahua kounga, nā te rapu haere i ngā wāhine āhei mā tētahi huarahi torotoro tangata. I whakahaeretia tētahi hui whakawhiti kōrero hei kohikohi raraunga, ā, ka tātaritia i muri mā te tātari ā-tāhuhu. Ko te pakeke o te hunga whakauru kei waenga i te 18 ki te 64 tau i te pānga o tō rātou roro ikura, ā, e ono ki te tekau mā waru tau i muri i te roro ikura ka whai wāhi ki te hui whakawhiti kōrero, i te tau 2021. E whā ngā tāhuhu, 11 hoki ngā tāhuhu whāiti i puta i roto i te tātaritanga raraunga: 1) ko ngā pānga o te roro ikura (te ekenga mai o te roro ikura me ngā wheako tuatahi, ngā pānga ā-tinana, ā-wairua, ā-hinengaro hoki, ngā panonitanga ki ō rātou tūranga mahi, ara mahi hoki); 2) te hauora whakaputa uri o ngā wāhine (te hapūtanga, te pire ārai hapū, te pānga o ngā rongoā whakakūtere toto ki te ikura wahine); 3) te whakahaere i a ia anō (te noho hei wahine, te aroturuki manaakitanga hauora, te taurima a te tangata i a ia anō); me te 4) tautoko (whakaroto, whakawaho anō hoki). He matatini ngā āhuatanga o ngā kawenga mō te wahine taitamariki i muri i te ikura, nā ngā āhuatanga tūraru, ngā tohu o te mate, me ngā hiahia mātūtū. Nā reira, me whakatupu rautaki whakamātūtū mō te wā roa mō ngā wāhine taitamariki, e kaha ake ai te whai hua o ngā mahi whakaora i muri i te roro ikura, me te ārainga i te pānga anō o te roro ikura. Ngā kupu matua: ngā wheako roro ikura; ngā pānga roro ikura; te whakamātūtūtanga i muri i te roro ikura; ngā tūraru roro ikura; mōrehu nō te roro ikura; ngā wāhine taitamariki

A CROSS SECTIONAL ANALYTICAL STUDY ON ADHERENCE AND PERSISTENCE OF CONTINUING SECONDARY PREVENTIVE MEDICINES FOR STROKE AT THE END OF 3 MONTHS IN A TERTIARY CARE CENTRE IN SOUTH INDIA

Prevalence of stroke in India is 90-222/100000 population. It causes so much morbidity to patient and family. Several classes of drugs are effective in preventing stroke recurrence by modifying the risk factors. There is limited data on long-term use of secondary prevention medications following stroke. Persistence is dened as the continuation of all medications patient was last prescribed at the end of 3 months. Adherence is dened as taking modied medications as per needs as per doctor's advice. A Methodology: ll patients with stroke both is chaemic and haemorrhagic and age more than 18 years , sustained in the one year when study is conducted as from the records of neurology department and attending the department for follow up are taken for study. A semi structured interview is done with them or their care givers to get information on their background characteristics, aetiology of stroke, comorbidities, cost of medication and affordability, various classes of medications administered and whether they are persistent in taking drugs, are they adherent to drugs, if not adherent/persistent ,reason for the same by open ended questions. A total of 260 patients were included, mean age was 58.5 years. Result: 78.5% had 3-month persistence and 3 month adherence 35.6%. Independent predictors of 3 month medication persistence included age more than 60 years, marital status, fewer medications prescribed at discharge and patients taking anti hypertensives . Most common reason for non-persistence was because the patients did not know why medication is being taken by them. Various factors play a role in persistence and adherenc Conclusion: e of medications in stroke. A multifactorial intervention including patient and health care providers are warranted, because of morbidity and mortality associated with every episode of stroke.

PO-03-135 LEFT ATRIAL APPENDAGE OCCLUSION VERSUS STANDARD OF CARE IN PATIENTS WITH ATRIAL FIBRILLATION AND A PRIOR THROMBO-EMBOLIC EVENT DESPITE ORAL ANTICOAGULANT THERAPY: A PROPENSITY SCORE MATCHED COMPARISON

Patients with atrial fibrillation (AF) that suffer from ischemic stroke despite oral anticoagulant (OAC) therapy have a very high risk of recurrent stroke and better prevention strategies are needed. Left atrial appendage occlusion (LAAO) is a promising secondary prevention strategy that may provide mechanical protection. However, evidence showing effectiveness of LAAO in this population is scarce and the current international guidelines only consider LAAO in patients with a contra-indication for OAC. To compare percutaneous LAAO to standard-of-care including continuing/switching OAC therapy for secondary stroke prevention in patients with AF and a prior thrombo-embolic event and/or LAA thrombus under OAC therapy. The STR-OAC LAAO cohort is an international collaboration of multiple LAAO registries (21 participating centers). All patients that underwent percutaneous LAAO because of a thrombo-embolic event and/or LAA thrombus on OAC were included. Propensity score matching with a previously published multi-center dataset of patients continuing/switching OAC therapy after a thrombo-embolic event was performed to compare the occurence of ischemic stroke between groups.Time-to-event analysis was performed with Kaplan-Meier curves and Cox-proportional-hazard regression analyses. A total of 425 patients underwent LAAO between 2010-2021 and were included in the STR-OAC LAAO cohort. Mean age was 72±9 years; 45% was female and mean CHA2DS2-VASc and HAS-BLED score were 4.8±1.5 and 2.8±1.2, respectively. Oral anticoagulation was discontinued after LAAO at discharge or after confirmation of adequate LAA closure at 1-3 months follow-up in most patients, the remaining 30% of patients continued OAC after LAAO as an adjunctive strategy. All LAAO patients were propensity-score matched and included in the primary outcome analysis. During follow up including 1450 patient-years a total of 59 patients experienced ischemic stroke: 1.9% per patient-year in LAAO group versus 9.2% per patient-year in the control group. LAAO was associated with a significantly lower risk of ischemic stroke (HR 0.3, 95%CI [0.2-0.5], p<0.001) compared to standard-of-care. In this propensity-score matched study, LAAO was associated with a lower risk of ischemic stroke compared to standard-of-care in patients with a thrombo-embolic event and/or LAA thrombus despite OAC treatment. Randomized controlled trial data may further confirm the effectiveness of LAAO in this very high-risk population.

Therapeutic Strategies for Ischemic Stroke

Ischemic stroke therapy consists of acute phase and preventive treatment strategies. Acute-phase ischemic stroke treatment includes systemic thrombolysis (rt-PA) and mechanical thrombectomy (endovascular therapy). Rt-PA is a very potent thrombolytic agent but its effectiveness is time-dependent. For the prevention of stroke recurrence (secondary stroke prevention) according to the TOAST classification, antiplatelet therapy (aspirin, clopidogrel, and cilostazol) is used for atherothrombotic and lacuna strokes, while anti-coagulant therapy (warfarin and direct oral anticoagulants [DOACs]) are used for cardiogenic cerebral embolism. Additionally, neuroprotective therapy using edaravone, a free radical scavenger, has recently been introduced to minimize brain tissue damage. Recently, neuronal regenerative therapies using stem cells have also been developed.

Gut microbiota and stroke: new avenues to improve prevention and outcome.

Despite major recent therapeutic advances, stroke remains a leading cause of disability and death. Consequently, new therapeutic targets need to be found to improve stroke outcome. The deleterious role of gut microbiota alteration (often mentioned as "dysbiosis") on cardiovascular diseases, including stroke and its risk factors, has been increasingly recognized. Gut microbiota metabolites, such as Trimethylamine-N-Oxyde (TMAO), Short Chain Fatty Acid (SCFA), and tryptophan, play a key role. Evidence of a link between alteration of the gut microbiota and cardiovascular risk factors exists, with a possible causality link supported by several pre-clinical studies. Gut microbiota alteration also seems to be implicated at the acute phase of stroke, with observational studies showing more non-neurological complications, higher infarct size and worse clinical outcome in stroke patients with altered microbiota. Microbiota targeted strategies have been developed, including prebiotics/probiotics, fecal microbiota transplantation, SCFA and TMAO inhibitors. Research teams have been using different time windows and endpoint for their studies, with various results. Considering the available evidence, we believe that studies focusing on microbiota targeted strategies in association with conventional stroke care should be conducted. Such strategies should be considered according to three therapeutic time windows: first, at the pre-stroke (primary prevention) or post-stroke (secondary prevention) phases, to enhance the control of cardiovascular risk factors. Secondly, at the acute phase of stroke, to limit the infarct size and the systemic complications and enhance the overall clinical outcome. Thirdly, at the subacute phase of stroke, to prevent stroke recurrence and promote neurological recovery.

Safety and Efficacy of Patent Foramen Ovale Device Closure: Evaluation of Outcomes in a Tertiary Referral Center

Abstract Aim and Objectives: Recent randomized controlled trials have demonstrated the benefit of patent foramen ovale (PFO) device closure over medical therapy alone for secondary prevention of cryptogenic stroke in carefully selected patients. In the current study, we sought to investigate the outcomes and complications of PFO device closure in our referral tertiary cardiovascular center. Materials and Methods: In this retrospective study, 155 adult patients who underwent PFO device closure between 2006 and 2021 were included. Patient characteristics, recurrent neurologic events, and procedure-related complications were evaluated. Results: The follow-up period was 2.3 ± 1.2 years. The average age of the participants was 41.3 ± 10 years, and 59.4% were male. Six patients (3.9%) suffered recurrent cerebrovascular events in the follow-up. No procedure-related complications were reported in our study population. Two patients (1.3%) with recurrent stroke had developed newly diagnosed atrial fibrillation (AF). Conclusion: PFO device closure is a safe and effective method for the prevention of recurrent ischemic stroke in patients with no other detectable etiology. Patients, particularly those with cardiovascular risk factors, should be meticulously investigated for the asymptomatic episodes of AF as the contributing factor with prolonged Holter monitoring or use of loop recorders.

Diagnostic Evaluation of Stroke Etiology.

Precise therapies require precise diagnoses. This article provides an evidence-based approach to confirming the diagnosis of ischemic stroke, characterizing comorbidities that provide insights into the pathophysiologic mechanisms of stroke, and identifying targets for treatment to optimize the prevention of recurrent stroke. Identifying the presence of patent foramen ovale, intermittent atrial fibrillation, and unstable plaque is now routinely included in an increasingly nuanced workup in patients with stroke, even as ongoing trials seek to clarify the best approaches for treating these and other comorbidities. Multicenter trials have demonstrated the therapeutic utility of patent foramen ovale closure in select patients younger than age 60 years. Insertable cardiac monitors detect atrial fibrillation lasting more than 30 seconds in about one in ten patients monitored for 12 months following a stroke. MRI of carotid plaque can detect unstable plaque at risk of being a source of cerebral embolism. To optimize the prevention of recurrent stroke, it is important to consider pathologies of intracranial and extracranial blood vessels and of cardiac structure and rhythm as well as other inherited or systemic causes of stroke. Some aspects of the stroke workup should be done routinely, while other components will depend on the clinical circumstances and preliminary testing results.

Ginkgo biloba extract EGb 761® improves cognition and overall condition after ischemic stroke: Results from a pilot randomized trial.

Background: Patients who experienced an ischemic stroke are at risk for cognitive impairment. Quantified Ginkgo biloba extract EGb 761® has been used to treat cognitive dysfunction, functional impairment and neuropsychiatric symptoms in mild cognitive impairment and dementia. Objectives: To assess the cognitive-related effects of EGb 761® treatment in patients after acute ischemic stroke, as well as the feasibility of patient selection and outcome measures. Methods: We conducted a randomized, multicentric, open-label trial at 7 centers in China. Patients scoring 20 or lower on the National Institutes of Health Stroke Scale were enrolled between 7 and 14days after stroke onset and randomly assigned to receive 240mg per day of EGb 761® or no additional therapy for 24weeks in a 1:1 ratio. Both groups received standard treatments for the prevention of recurrent stroke during the trial. General cognitive function and a battery of cognitive tests for sub-domains were evaluated at 24weeks. All patients were monitored for adverse events. Results: 201 patients ≥50years old were included, with 100 assigned to the EGb 761® group and 101 to the reference group. The mean change from baseline on the global cognitive function as assessed by the Montreal Cognitive Assessment score was 2.92 in the EGb 761® group and 1.33 in the reference group (between-group difference: 1.59 points; 95% confidence interval [CI], 0.51 to 2.67; p < 0.005). For cognitive domains, EGb 761® showed greater effects on the Hopkins Verbal Learning Test Total Recall (EGb 761® change 1.40 vs. reference -0.49) and Form 1 of the Shape Trail Test (EGb 761® change -38.2 vs. reference -15.6). Potentially EGb 761®-related adverse events occurred in no more than 3% of patients. Conclusion: Over the 24-week period, EGb 761® treatment improved overall cognitive performance among patients with mild to moderate ischemic stroke. Our findings provide valuable recommendations for the design of future trials, including the criteria for patient selection. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN11815543.

Detection of Atrial Fibrillation in Patients Admitted with Ischaemic Stroke: A Non-systematic Review of the Asian Population

Stroke with AF is often associated with high recurrence rates. However, many patients with ischaemic stroke do not have a history of AF and show sinus rhythm and the absence of AF on their admission ECG. The detection of AF remains challenging due to its intermittent nature. Therefore, the ultimate goal of cardiac monitoring after cerebral ischaemic events is to detect AF so that oral anticoagulants can be prescribed to prevent the recurrence of a second, more debilitating or fatal stroke. In this article, AF detection in hospitalised patients with ischaemic stroke is discussed, with a focus on the Asian population. The AF detection rates in Asian cohorts are compared with those of major studies in the Western population; the utility and limitations of various cardiac monitoring modalities in Asian populations and healthcare systems and emerging technologies that could potentially detect AF in the stroke population are summarised and clinical practice and evidence gaps in detecting AF to prevent stroke recurrence are discussed.

Absence of susceptibility vessel sign and hyperdense vessel sign in patients with cancer-related stroke.

Identification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients. SVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression. Of the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45-6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73-13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54-2.11). The absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care.

Isolated Insular Stroke: An Interesting Report of Two Cases.

Isolated Insular Stroke: An Interesting Report of Two Cases.

Dual Antiplatelet Therapy Role in Acute Ischemic Stroke

Stroke is the second greatest cause of mortality and one of the top causes of long-term disability. The fatality rate and age-adjusted prevalence of stroke have decreased globally over the past quarter-century. However, the absolute number of stroke cases has climbed, as populations have grown older. Initiating antiplatelet medications early in patients with acute ischemic stroke (AIS) is essential for preventing stroke recurrence. Aspirin, clopidogrel, and dipyridamole are the most commonly used antiplatelet medications worldwide. Combining antiplatelet drugs is associated with an increased risk of bleeding when used for long-term prophylaxis. The use of Dual antiplatelet treatment (DAPT) for a shorter duration is associated with a lower risk than long-term usage. The best period of treatment for transient ischemic attack (TIA) and mild ischemic stroke appears to be between 21 and 30 days.

Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Abstract TP101: Reduced Left Atrial Strain In Embolic Stroke Of Undetermined Source Is Associated With Atrial Fibrillation Detected On Mobile Cardiac Monitoring

Recent studies have failed to reveal benefit of anticoagulation over antiplatelet therapy in the prevention of recurrent stroke in Embolic Stroke of Undetermined Source (ESUS) patients. This is attributed to significant heterogeneity in underlying mechanisms of ESUS. Atrial fibrillation (AF) is a potential cause of ESUS, and evaluating left atrial (LA) function by measuring LA strain by speckle tracking echocardiography (STE) is an emerging technique to assess LA biomechanics. Our study investigates the relationship between LA strain and AF detection in ESUS patients. We included hospitalized patients with ESUS subtype who underwent STE. LA function by assessing three phases of LA strain (reservoir, conduit and contractile) were retrospectively quantified and evaluated. Several patients were discharged with mobile cardiac telemetry that was retrospectively reviewed for AF detection. Descriptive statistical methods and both unadjusted and adjusted regression models were used. Among 325 ESUS patients, mean age was 66.5±15.0, 49% were male, 49% had outpatient cardiac monitoring, and 25% had AF detected. LA reservoir (25.17±13.4 vs 32.43±18.13), LA contractile (11.95±9.66 vs 16.67±10.94) and LA conduit (13.08±6.47 vs 17.20±12.21) strains were significantly lower in patients with AF detected compared to patients without AF detected. In the unadjusted binary logistic regression analysis, patients with AF detected had significantly lower LA reservoir (OR 0.967, 95% CI 0.941-0.994), LA contractile (OR 0.957, 95% CI 0.918-0.997) and LA conduit (OR 0.961, 95% CI 0.925-0.998) strains. This significance was lost after adjusting for age. Our study demonstrates that reduced LA strain is associated with subsequent detection of AF in ESUS patients. We believe that routine LA strain measurement can aid clinicians in identifying ESUS patients with high AF prevalence and thereby appropriately target patients for anticoagulation therapy to prevent subsequent strokes.

PS-BPB07-1: DEVELOPMENT OF ANTI-THROMBOTIC VACCINE AGAINST HUMAN S100A9

Background &amp; Purposes: In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we have reported that a newly designed antiplatelet vaccine against S100A9 could prevent thrombosis in the middle cerebral artery in mice by inhibiting S100A9/CD36 signaling in platelets. However, the difference in amino acid sequences in epitopes between mice and humans might be problematic for clinical use. In the present study, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys. Methods: First, we screened several candidate epitopes in mice and the selected epitope in human S100A9, which is common in monkey S100A9, was conjugated to Keyhole limpet hemocyanin. A mixture of the vaccine and Alum adjuvant was subcutaneously injected into 4 cynomolgus monkeys, three times every two weeks. Antibody production against human S100A9 was examined by ELISA or western blotting. Anti-thrombotic effects in collagen-induced thrombosis were examined in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey using an automated microchip flow-chamber system. Bleeding time was evaluated in two monkeys. Results: Based on results of computed epitope prediction, we first assessed whether 2 to 11, 97–106, or 104–113 amino acids, where the amino acid sequence is approximately similar between humans and monkeys, could raise antibodies against S100A9 in mice. Compared with the vaccine for the 2–11 amino acids epitopes, 97–106 amino acids and 104–113 amino acids demonstrated higher antigenicity, indicating that epitopes in the C-terminus are stronger than those in the N-terminus. Based on this result, we selected 102 to 112 amino acids as the epitope for the human S100A9 vaccine. When the monkeys were vaccinated, antibody titers against human S100A9 were significantly increased. Western blotting analysis showed that the produced antibody recognized human S100A9. Although the addition of pre-vaccinated serum into fresh whole blood did not affect thrombus formation, post-vaccination serum inhibited collagen-induced thrombosis formation in two monkeys. Anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects by vaccination. Notably, prolongation of bleeding time was not observed in vaccinated monkeys. Conclusions: Anti-human S100A9 vaccine revealed anti-thrombotic effects in some monkeys without affecting bleeding time. Although further studies are necessary to increase the effects and warrant the safety aspects, this vaccine could clarify the use of an anti-thrombotic vaccine in clinical settings.

Cancer-Associated Stroke and Acute Endovascular Reperfusion Therapy.

Since stroke is often associated with cancer, acute stroke patients with cancer undergoing endovascular therapy (EVT) are not uncommon. Reportedly, the proportion of such cases is approximately 6%-7% of all stroke EVT cases. Ischemic stroke in patients with active cancer (cancer-associated stroke) includes not only strokes caused by cancer-related hypercoagulability but also coincident strokes due to common etiologies, strokes associated with tumor emboli, direct tumor invasion of blood vessels, and strokes associated with cancer therapy. Stroke caused by cancer-related hypercoagulability itself encompasses various entities, including paradoxical embolism, stroke due to nonbacterial thrombotic endocarditis, and in situ arterial occlusion due to disseminated intravascular coagulation or thrombotic microangiopathy. Thus, diverse mechanisms contribute to cancer-associated stroke, emphasizing the need to consider individualized treatment strategies for acute cases involving large vessel occlusion. Observational studies have shown that EVT for cancer-associated stroke results in poorer clinical outcomes, but with comparable rates of successful reperfusion and symptomatic intracranial hemorrhage when compared with stroke patients without cancer. This suggests that denying patients EVT solely on the basis of comorbid active cancer is inappropriate, and decision-making should be shared with the patients and their families, preferably through a multidisciplinary team approach. Thrombi retrieved from patients with stroke caused by cancer-related hypercoagulability have unique characteristics, being predominantly platelet rich and difficult to retrieve. Preprocedural imaging and serum biomarkers, including the hyperdense vessel sign on non-contrast CT, susceptibility vessel sign on T2* or susceptibility-weighted MRI, three-territory sign on MRI, and D-dimer levels, are valuable in evaluating the stroke subtype and thrombus features. Thrombectomy techniques, such as contact aspiration and stent retriever monotherapy, have shown varying degrees of effectiveness for stroke caused by cancer-related hypercoagulability, warranting further study. After reperfusion therapy, appropriate treatment for the prevention of stroke recurrence should be initiated, considering the specific stroke subtypes. In conclusion, cancer-associated stroke encompasses diverse subtypes, and thrombi associated with stroke caused by cancer-related hypercoagulability present various challenges for thrombectomy. Individualized treatment approaches based on underlying mechanisms are essential for improving outcomes in acute stroke patients with active cancer. Optimization of preprocedural diagnosis, EVT techniques, and secondary prevention of stroke caused by cancer-related hypercoagulability will lead to better management of these patients and enhance their quality of life.

PS-P04-10: IMPACT OF BLOOD PRESSURE VARIABILITY ON THE RISK OF STROKE AND PREMATURE DEATH

Objective: Visit-to-visit blood pressure variability (BPV) has been identified in several recent studies as a risk factor for stroke, independently of the level of BP. If true, this finding could help to identify patients at higher risk of stroke and to develop new preventive strategies. However, studies on BPV are exposed to important methodological challenges including conditioning on the future, which violates the assumption of the Cox model, using endogenous variables like the expected BP and its variance, and not handling properly the measurement error. Our objective was to address these issues by designing a joint model with heterogeneous variance for the repeated measures of BP, allowing us to analyze the association between BPV and the risk of stroke and the competing risk of death. Design and Method: We used data from PROGRESS (Perindopril Protection against Stroke Study), a placebo-controlled BP-lowering randomized trial for the prevention of stroke recurrence in 6105 patients with a previous history of stroke or TIA. During 5 years of follow-up, BP was measured 12 times, and 727 strokes and 438 non-stroke deaths were observed. We designed an innovative and dedicated joint model combining a linear mixed model, including a subject-specific random effect for the residual variance and two proportional hazard models for the two competing risks of stroke and death. In this model, the risk of each event may depend on the current value and current slope of the individual expected trajectory of BP as well as the intra-subject residual variance. Results: In separate analysis of each arm of the trial, we found that the risk of stroke increased with the current level of BP (HR = 1.13 per 5 mmHg, 95%CI = [1.08; 1.17], p-value &lt; 0.001) but was not associated with its intra-individual variability (HR = 0.89, 95%CI = [0.71; 1.12], p-value = 0.317). Conversely, the risk of non-stroke death increased with the intra-individual variability of BP (HR = 1.43, 95%CI = [1.08; 1.88], p-value = 0.011) but not with its current level (HR = 1.03, 95%CI = [0.97; 1.09], p-value = 0.317). Results were similar on the complete sample adjusting for the randomized treatment. Conclusion: Using appropriate modeling accounting for measurement error and limiting selection and other potential biases, we found a differential effect of expected BP and BPV on the risk of stroke and of death. These results, if confirmed and enlarged to other populations, would have important consequences to design efficient and individualized preventive strategies.