Rate Of Recurrent Stroke Research Articles

Non-vitamin K Oral Anticoagulants and Anti-seizure Medications: A Retrospective Cohort Study.

Purpose: Concerns of drug–drug interactions (DDIs) between anti-seizure medications (ASMs) and non-vitamin K oral anticoagulants (NOACs) have emerged in recent case reports and guidelines. Theoretically, the induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme and permeability glycoprotein (P-GP) efflux transporter protein systems may reduce the effect of NOACs. We aimed to investigate whether such DDIs are clinically relevant in a real-world situation.Methods: We retrospectively reviewed 320 ischemic stroke patients with atrial fibrillation (Af) and grouped them according to different potential interactions with CYP3A4 and P-GP. Ischemic stroke events, transient ischemic attack (TIA) events, follow-up duration, baseline characteristics, concomitant ASMs, and stroke risk factors were collected. Statistical analysis included Kaplan–Meier survival curves and the log-rank test.Results: Overall, 320 ischemic stroke with Af patients received NOACs. Among the NOAC users, 75 also took ASMs, including 56 that have potential DDIs: 43 (13.4%) were categorized as potential CYP and P-GP DDIs and 13 (4.1%) as P-GP-only DDIs. The remaining 264 (82.5%) patients were used as controls including 19 exposed to nonsignificant DDI ASMs and 245 patients without ASM exposure. The incidence rates of recurrent stroke/TIA events in both CYP3A4 and P-GP DDIs, P-GP DDIs only, and no DDIs were 7.5, 2.1, and 8.4/100 person-years, respectively. Kaplan–Meier survival curves and the log-rank test did not show significant differences among the groups.Conclusions: The recurrent stroke rate of NOAC users with potential DDIs was not higher than in those without potential DDIs in this single-institute study. Our results suggest that theoretical interactions between ASMs and NOACs may not be as severe as previously thought in a real-world situation.

Two-State Kinetic Model of Rates of Stroke Recurrence in the POINT Study Population.

Following an acute ischemic stroke or transient ischemic attack, 2 rates of stroke recurrence are suggested by data from trials of acute secondary prevention treatments: a transient rapid rate followed by a persisting slower rate of stroke. A kinetic model was constructed based on underlying vulnerable and stabilized states of patients following acute ischemic events related by fixed transition rates. Its predictions were fitted by nonlinear regression to the observed timing of outcome events in patients in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). The modeled survivor function produced a close fit to the observed data. The model's predicted kinetic rates suggest that, among subjects in the control group, the event rate was 100-fold higher in the vulnerable state than in the stabilized state. Active treatment halved this rapid rate and had little effect on event rates in the stabilized state. If at least one-tenth of the study population began in the vulnerable state, the rate of transition from the vulnerable to the stabilized state was still faster, with a half-life of only 1 to 2 days. Examination of kinetics of stroke occurrence, and of the rates associated with modeled state transitions, may provide insights into the underlying pathophysiological events that are targets for acute secondary prevention of stroke.

Cilostazol for secondary stroke prevention: systematic review and meta-analysis

BackgroundStroke is one of the leading causes of death worldwide. Cilostazol, an antiplatelet and phosphodiesterase 3 inhibitor, has not been clearly established for ischaemic stroke use. We aim to determine...

Risk factor control after ischemic stroke or transient ischemic attack.

We aimed to estimate the status of risk factor control after ischemic stroke or transient ischemic attack (IS/TIA), and the influence on recurrent stroke in rural communities of northeastern China. This population-based, prospective cohort study enrolled adults aged ≥35years residing in rural northeastern China. We conducted cardiovascular health examinations in 2012-2015 and followed up in 2018 to record any cardiovascular event. Control of risk factors after IS/TIA was determined through a baseline survey. The Cox proportional hazard model was used to evaluate the relationship between uncontrolled risk factors and stroke recurrence. Of the 10,700 participants, 575 were diagnosed with IS/TIA and were included in the analysis. At baseline, the rates of control of risk factors were as follows: fasting plasma glucose (FPG), 81.6%; not currently smoking, 65.7%; and achieving physical activity targets, 61%. Blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI) were poorly controlled (28.3%, 26.3%, and 37.4%, respectively). The rate of stroke recurrence was 12% during a median follow-up of 4.43years. After adjusting for age, sex, ethnicity, family history of stroke, and current drinking, uncontrolled BP and not achieving physical exercise targets were associated with an increased risk of recurrence (hazard ratios: 2.081, 1.685, respectively; p<.05). Uncontrolled FPG, BMI, or LDL-C and current smoking did not significantly influence recurrent risk (p>.05). Control of risk factors after IS/TIA needs to be improved in rural communities of northeastern China to prevent recurrence and thus alleviate the public health and economic burden of stroke.

Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention.

Background and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk. Methods Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months. Results Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk. Conclusions There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

Long-term outcomes of postoperative atrial fibrillation following non cardiac surgery: A systematic review and metanalysis

BackgroundNew-onset atrial fibrillation (AF) in non-cardiac postoperative setting is common and is associated with a high risk of in-hospital mortality and morbidity. The long-term risks of stroke, mortality and AF recurrence rate in patients with postoperative AF (POAF) are unclear. MethodsWe performed a systematic literature review in electronic databases from inception to March 5th, 2020 of studies reporting the incidence of stroke, mortality and AF recurrence in patients with POAF. We confined our analysis to studies with a cohort of at least 150 patients with POAF and with a median follow-up of 12 months as a minimum. Odds Ratios (OR) were pooled using a random-effects model. ResultsQualitative analysis included 8 studies (7 observational cohort studies and 1 randomized controlled trial) enrolling 3,718,587 patients. Six studies underwent metanalysis comprising 17,684 postoperative patients with POAF and 2,169,248 postoperative patients without POAF. The development of POAF conferred a four-fold increased risk of stroke in the long-term [OR 4.05; 95% confidence interval (CI) 2.91–5.62]. Mortality in the two studies reporting long-term data was higher in patients with POAF compared to those without POAF (OR 3.59; CI 95% 2.84–4.53). Data about recurrence were too heterogeneous to undergo metanalysis. ConclusionsPOAF is associated with a greater risk of stroke and mortality over the long-term period. Studies focusing on AF recurrence are needed to address the perception of POAF as a benign transient entity. The increased mortality risk following POAF should encourage systematic detection and prevention of this arrhythmia.

The Effects of Preoperative Coronary Collateral Circulation on Cardiac-Related Events after Coronary Artery Bypass Graft Surgery.

IntroductionThis study aimed to evaluate the effects of coronary collateral circulation (CCC) in patients who had undergone coronary artery bypass grafting (CABG).MethodsA total of 127 patients who had undergone CABG (2011-2013) were enrolled into this study and follow-up was obtained by phone contact. Patients were categorized into two groups according to preoperative CCC using the Rentrop method. Percutaneous coronary intervention (PCI), recurrent myocardial infarction (MI), stroke, heart failure (HF), and mortality rates were compared between groups. Clinical outcome was defined as combined end point including death, PCI, recurrent MI, stroke, and HF.ResultsSixty-two of 127 patients had poor CCC and 65 had good CCC. There were no differences in terms of PCI, recurrent MI, and HF between the groups. Stroke (seven of 62 [11.3%] and one of 65 [1.5%], P=0.026) and mortality (19 of 62 [30.6%] and 10 of 65 [15.4%], P=0.033) rates were significantly higher in poor CCC group than in good CCC group. In Kaplan-Meier analysis, survival time was not statistically different between the groups. Presence of poor CCC resulted in a significantly higher combined end point incidence (P=0.011).ConclusionStroke, mortality rates, and combined end point incidence were significantly higher in poor CCC patients than in the good CCC group.

Diagnostic and Prognostic Value of Novel Echocardiographic Biomarkers in Identification of Cardioembolism and Prediction of Outcomes in Patients with Stroke of Undetermined Source

Strokes of undetermined source, commonly termed cryptogenic stroke (CS), account for a significant proportion of ischaemic stroke aetiology and have high rates of stroke recurrence. The heterogeneous aetiology of CS makes decisions regarding treatment for such patients challenging. We sought to evaluate the diagnostic and prognostic value of novel measures of left atrial (LA) function in identification of cardioembolism and prediction of outcomes in patients with CS.

Efficacy of aspirin, clopidogrel, and ticlopidine in stroke prevention: A population-based case-cohort study in Taiwan.

In real-world practice settings, there is insufficient evidence on the efficacy of antiplatelet drugs, including clopidogrel, aspirin, and ticlopidine, in stroke prevention. To compare the efficacies between aspirin and clopidogrel and aspirin and ticlopidine in stroke prevention. This population-based case-cohort study utilized the data obtained from a randomized sample of one million subjects in the Taiwan National Health Insurance Research Database. Patients who were hospitalized owing to the primary diagnosis of ischemic stroke from January 1, 2000 to December 31, 2010 and treated with aspirin, ticlopidine, or clopidogrel were included in the study. Propensity score matching with a 1:4 ratio was performed to compare aspirin with ticlopidine and clopidogrel. The criteria for inclusion were the use of one of the three antiplatelet drugs for more than 14 days within the first month after the stroke and then continued use of the antiplatelet drugs until the study endpoint of recurrent stroke. During the 3-year follow-up period, the recurrent stroke rates were 1.62% (42/2585), 1.48% (3/203), and 2.55% (8/314) in the aspirin, ticlopidine, and clopidogrel groups, respectively. Compared with the patients treated with aspirin, those treated with clopidogrel and ticlopidine showed competing risk-adjusted hazard ratios of recurrent stroke of 2.27 (1.02-5.07) and 0.62 (0.08-4.86), respectively. Compared with the patients treated with aspirin, those treated with clopidogrel were at a higher risk of recurrent stroke. For stroke prevention, aspirin was superior to clopidogrel whereas ticlopidine was not inferior to aspirin.

Ефективність противірусної терапії у вторинній профілактиці ішемічного інсульту на тлі маніфестації вірусної інфекції

Recurrent stroke remains the key health issue in the world. A higher three-year recurrence rate of stroke in patients with persistence of the genome of herpes viruses, and with presence in the blood of the genome of at least 2 types of viruses was identified. These investigations demonstrate the importance of further research into the role of antiviral therapy in improving the rehabilitation and secondary prevention of stroke in patients with persistent viral infection The purpose of the study was to evaluate the effectiveness of antiviral therapy in the secondary ischemic stroke prevention on the viral infection manifestation background. Material and methods. The study included 105 patients with moderate to severe ischemic stroke with a viral manifestation confirmed by the detection of herpes virus’s DNA (HSV1, HSV2, EBV, CMV, HHV6) and Flu RNA. Patients who were additionally prescribed antiviral drugs on the background of traditional therapy were in the main group (n = 35). Patients who received only traditional, recommended by the modern stroke treatment guidelines, therapy and secondary stroke prevention measures were included in the comparison group (n = 70). Results and discussion. We found that the effectiveness of the proposed preventive treatment depended on the viral load of the patient. In the presence of three or more types of viruses, the proposed therapy provided a significantly lower ischemic stroke recurrence rate, compared to the patients who did not receive antiviral therapy 11.1% vs. 49.8%, p = 0.042. Prevention of recurrent ischemic stroke, which should have started as soon as possible after the development of the first stroke or transient ischemic attack occurrence, F. Rincon and R. L. Sacco (2008) consider the most relevant in this group of patients. Herewith, as emphasized by D. G. Hackam and J. D. Spence (2007), comprehensive prevention has reduced the risk of recurrent ischemic stroke by almost 80%, thus preventing 4 out of 5 possible disorders. However, both native and world literature still has a lack of systematic data of the problem of antiviral therapy using in patients with acute disorders of cerebral circulation, although it has been proven that infectious and inflammatory complications are an important pathogenetic factor of its unfavorable and severe outcome. M. S. Elkind et al. (2016) consider that antiviral drugs such as acyclovir may play an appropriate role in the prevention of recurrent ischemic stroke in children if their causal relation is confirmed. Conclusion. The use of acyclovir in complex rehabilitation therapy and secondary stroke prevention in patients with viral infection manifestation provided an increase in the average score of Bartel index after 1 year, p = 0.017. In the case of antiviral therapy using in the complex prevention of recurrent vascular events in patients with viral infection manifestation, the three-year recurrence rate of stroke is lower (p = 0.042)

Conventional Angiography in the Assessment of Recently Symptomatic Patients with Ipsilateral Carotid Stenosis

Background and PurposeBenefits of revascularization for moderate and severe (≥50%) carotid stenosis were established based on digital subtraction angiography (DSA). We aimed to assess the discrepancy between invasive and non-invasive angiography in a consecutive, prospective cohort of patients with recent stroke and non-invasive imaging suggesting ≥50% ipsilateral carotid stenosis. Materials and MethodsWe reviewed prospectively-collected data for consecutive patients admitted with recent stroke/TIA and ≥50% ipsilateral carotid stenosis on non-invasive imaging over 28 months. All patients underwent DSA to confirm the degree of stenosis per NASCET criteria. All patients with <50% stenosis by DSA were treated with medical therapy only and their recurrent event rates were assessed at 6 months. Results148 symptomatic patients with ≥50% ipsilateral carotid stenosis on CTA (82%) and MRA (18%) underwent DSA to confirm degree of stenosis. Median age was 73 years and 64% were male. DSA demonstrated <50% stenosis in 28 patients (19%). Median presenting NIHSS was 1 (IQR 0-3). Median carotid stenosis evaluated by non-invasive imaging was 70% (IQR 60-85%) and by DSA was 40% (IQR 30-45%). One of 28 patients (4%) experienced recurrent nondisabling stroke (NIHSS 1) after stopping dual antiplatelet therapy. ConclusionIn nearly one-in-five cases with recent stroke due to ipsilateral carotid stenosis deemed to be candidates for revascularization based on CTA or MRA, DSA led to institution of medical therapy only due to insufficiently severe stenosis. In patients treated with medical therapy based on the findings of <50% stenosis on DSA, the rate of recurrent stroke is low.

Economic evaluation of extended electrocardiogram monitoring for atrial fibrillation in patients with cryptogenic stroke.

Timely identification of occult atrial fibrillation following cryptogenic stroke facilitates consideration of oral anticoagulation therapy. Extended electrocardiography monitoring beyond 24 to 48 h Holter monitoring improves atrial fibrillation detection rates, yet uncertainty remains due to upfront costs and the projected long-term benefit. We sought to determine the cost-effectiveness of three electrocardiography monitoring strategies in detecting atrial fibrillation after cryptogenic stroke. A decision-analytic Markov model was used to project the costs and outcomes of three different electrocardiography monitoring strategies (i.e. 30-day electrocardiography monitoring, three-year implantable loop recorder monitoring, and conventional Holter monitoring) in acute stroke survivors without previously documented atrial fibrillation. The lifetime discounted costs and quality-adjusted life years were $206,385 and 7.77 quality-adjusted life years for conventional monitoring, $207,080 and 7.79 quality-adjusted life years for 30-day extended electrocardiography monitoring, and $210,728 and 7.88 quality-adjusted life years for the implantable loop recorder strategy. Additional quality-adjusted life years could be attained at a more favorable incremental cost per quality-adjusted life year with the implantable loop recorder strategy, compared with the 30-day electrocardiography monitoring strategy, thereby eliminating the 30-day strategy by extended dominance. The implantable loop recorder strategy was associated with an incremental cost per quality-adjusted life year gained of $40,796 compared with conventional monitoring. One-way sensitivity analyses indicated that the model was most sensitive to the rate of recurrent ischemic stroke. An implantable loop recorder strategy for detection of occult atrial fibrillation in patients with cryptogenic stroke is more economically attractive than 30-day electrocardiography monitoring compared to conventional monitoring and is associated with a cost per quality-adjusted life year gained in the range of other publicly funded therapies. The value proposition is improved when considering patients at the highest risk of recurrent ischemic stroke. However, the implantable loop recorder strategy is associated with increased health care costs, and the opportunity cost of wide scale implementation must be considered.

Patent Foramen Ovale Closure: State of the Art.

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people, it is a benign finding; however, in some people, the PFO can open widely to enable paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of the PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised control trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this article considers the evidence for PFO closure in cryptogenic stroke. The article also addresses other potential indications for closure, including systemic arterial embolisation, decompression sickness, platypnoea–orthodeoxia syndrome and migraine with aura. The article lays out the pre-procedural investigations and preparation for the procedure. Finally, the article gives an overview of the procedure itself, including discussion of closure devices.

Abstract 13293: Detection of Atrial Fibrillation by Implantable Loop Recorders Following Cryptogenic Stroke: A Retrospective Study of Predictive Factors and Outcomes

Introduction: Cryptogenic strokes account for up to 40% of ischemic strokes. Atrial fibrillation (AF) is a known cause of ischemic stroke. Current data shows that occult AF can be detected by implantable devices at higher rates than conventional cardiac rhythm monitoring. There are, however, limited data available on risk factors and outcomes associated with AF detection by implantable loop recorders (ILRs). Objective: To investigate the risk factors and outcomes associated with occult AF detected by ILR in patients with cryptogenic stroke. Methods: We conducted a retrospective chart review of patients admitted with cryptogenic stroke at Ascension St John Hospital and Ascension Macomb-Oakland Hospital in Michigan who had ILRs placed from 1/1/2016 to 1/31/2020. Data were collected on demographics, comorbidities, treatment and outcomes. AF detection was defined as continuous AF for 30 seconds. Data were analyzed using Student’s t-test, the χ2 test and logistic regression. Results: We reviewed 172 patients, 52.3% male, 56.4% white, mean age 62.7 ± 13.6 years. The incidence of AF detection by ILR was 14% (24/172) over a mean follow-up of 12.75 ± 10.71 months. The mean duration of monitoring prior to AF detection was 4.5 months (range:1 day to 14 months). The median duration of AF was 6 minutes (range: 37.2 seconds to 11.3 hours). From univariable analysis, older age (p=0.03), male sex (p=0.09), embolic stroke pattern on imaging (p=0.06), and lack of AF symptoms (p=0.001) were associated with AF detection by ILR. From multivariable analysis, patients with detected AF were more likely to be older (OR=1.04, p=0.04), male (OR=3.6, p=0.03), asymptomatic (OR=6.3, p=0.01), and have an embolic stroke pattern on imaging (OR=3.3, p=0.04). 95.7% of patients with confirmed AF were started on anticoagulation for secondary stroke prevention. There was no difference in the incidence of stroke post-hospitalization between those with AF detection and those without (16% vs. 16.4%, p=0.96). Conclusions: In patients with cryptogenic stroke, age, gender, stroke pattern, and lack of AF symptoms are independent predictors of occult AF detection by ILR. Most patients with confirmed AF were started on anticoagulation for secondary stroke prevention and had low stroke recurrence rates.

Anticoagulation and Risk of Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source Having No Potential Source of Embolism

Background: This study aimed to determine whether use of oral anticoagulants (OACs) was associated with a reduced risk of recurrent stroke compared with use of antiplatelets (APs) in patients with embolic stroke of undetermined source (ESUS) having no potential source of embolism. Methods: Of 8,790 patients with acute ischemic stroke registered at 7 centers in the Fukuoka Stroke Registry from June 2007 to May 2017, we included 681 patients (mean age 69.7 [SD 14.1] years, 48.3% men) who experienced ESUS without a potential source of embolism and received OAC alone or AP alone. We estimated hazard ratios (HRs) and 95% confidential intervals (CIs) of recurrent ischemic stroke or any stroke after discharge using a Cox proportional hazards model and Fine and Gray model. Results: During a mean follow-up of 3.4 (SD 1.7) years, event rates of recurrent ischemic stroke were 4.4 per 100 person-years in 489 patients treated with AP and 2.0 per 100 person-years in 192 patients treated with OAC. OAC use was associated with a reduced risk of recurrent ischemic stroke, even after adjusting for potential confounding factors (multivariable-adjusted HR [95% CI], 0.42 [0.23–0.80]) and when additionally considering death as a competing risk (0.45 [0.24–0.85]). The reduced risk of recurrent ischemic stroke was still observed in patients treated with OAC (0.32 [0.15–0.67]) in reference to propensity score-matched patients treated with AP. These associations were maintained for all types of stroke, including ischemic and hemorrhagic stroke. Conclusions: This nonrandomized observational study suggests that anticoagulation therapy might be associated with a reduced risk of recurrent stroke compared with antiplatelet therapy in patients with ESUS in whom no potential source of embolism was identified. Further study should be performed in consideration of a potential source of embolism even in patients with ESUS.

Clinical Presentation and Stroke Incidence Differ by Moyamoya Etiology.

Moyamoya arteriopathy, which can be idiopathic or associated with sickle cell disease, neurofibromatosis, Down syndrome, or cranial radiation therapy, is a progressive cerebral arteriopathy associated with high rates of incident and recurrent stroke. Little is known about how these subgroups differ with respect to clinical presentation, radiographic findings, stroke risk, and functional outcomes. Using ICD codes, we identified children ages 28 days to 18 years treated for moyamoya arteriopathy at our tertiary care center between 2003 and 2019. Demographic, clinical, and radiographic data were extracted from the medical record. The Pediatric Stroke Recurrence and Recovery Questionnaire was administered to consenting participants. Sixty-nine patients met inclusion criteria (33 idiopathic, 18 sickle cell disease, 11 neurofibromatosis, 6 Down syndrome, 1 cranial radiation therapy). Median follow-up time was 7.7 years; 24 patients had at least 5 years of follow-up data. Frequency of stroke at presentation differed by subgroup (P < .001). Of patients with at least 2 years of follow-up, 33 (55%) experienced stroke. The proportion of patients experiencing stroke differed by subgroup (50% of idiopathic cases, 72% of sickle cell disease, 11% of neurofibromatosis, and 100% of Down syndrome, P = .003). The frequency of bilateral versus unilateral disease (P = .001) and stroke-free survival following presentation (P = .01) also differed by subgroup. In this single-center cohort, moyamoya subgroups differed with respect to clinical and radiographic characteristics, with neurofibromatosis-associated moyamoya syndrome having a milder phenotype and Down syndrome-associated moyamoya portending a more aggressive course. These findings need confirmation in a larger, multi-center cohort with longer duration of follow-up.

Risk of Recurrence of Symptomatic Intracranial Atherosclerosis in Posterior Circulation Seen to Be Higher Than That in Anterior Circulation in Long-Term Follow-Up.

Background: Intracranial atherosclerotic stenosis (ICAS) is an important cause of ischemic stroke. In Asians, intracranial atherosclerotic disease leads to 33–50% of ischemic events. At present, treatment with medication vs. endovascular therapy (EVT) for symptomatic ICAS (sICAS) patients is still debatable. The clinical prognosis of patients who are not completely free of stroke symptoms despite regular medication and are not eligible for EVT for various reasons, is not yet investigated.Aim: To report the long-term recurrence rate of stroke in a cohort of symptomatic ICAS patients who intended to undergo EVT upon admission but could not for various reasons after digital subtraction angiography (DSA) evaluation.Method: This is a retrospective analysis of consecutive sICAS patients in a single center from January 1, 2016 to August 31, 2017 who underwent DSA assessment alone and were not eligible for further EVT. Demographic information, risk factors related to cerebrovascular disease, clinical comorbidities, medication, imaging data, and long-term outcomes were reported.Results: A total of 218 patients were included in the study; 42 (19.2%) patients had recurrence of stroke/transient ischemic attack (TIA) at the 1-year follow up. Patients were divided into two groups according to lesions in anterior circulation (n = 120) or posterior circulation (n = 98). There was a higher stroke/TIA recurrence rate in the posterior circulation than anterior circulation group (25.5 vs. 14.2%, p = 0.035). Given the advanced age, higher prevalence of coronary heart disease, larger stenosis length, and poorer collateral circulation, the posterior circulation group showed a higher risk of recurrent stroke/TIA and death than the anterior circulation group [HR = 3.092, 95% CI (1.335–7.164), p = 0.0084], after adjusting for all confounding factors in the COX regression model. Kaplan–Meier analysis showed that sICAS recurrence and mortality risk in the posterior circulation group was consistently higher than that in the anterior circulation group (log-rank-test, p = 0.033).Conclusions: Patients with posterior circulation sICAS have higher recurrence risk than those with anterior circulation managed with medication alone. Further, posterior circulation lesion is an independent risk factor for recurrence in sICAS patients.

Low- Versus Moderate-Dose Hydroxyurea for Secondary Stroke Prevention in Children with Sickle Cell Disease in Sub-Saharan Africa: Final Results of a Randomized Controlled Trial, Sprint Trial

Introduction Strokes are a preventable cause of neurological morbidity and premature death, particularly in children with sickle cell anemia (SCA) living in low-resource countries. If untreated, 50% of children with SCA their first overt ischemic stroke will have a recurrent stroke within two years of the event. In high-income countries, ASH 2020 guidelines recommend indefinite regular blood transfusion therapy for secondary stroke prevention (Blood Adv. 2020). Unfortunately, regular blood transfusion therapy is not a feasible option for children with SCA in sub-Saharan Africa due to the high cost of monthly blood transfusion, limited blood supply, and unsafe transfusion practices. Also, children who receive regular blood transfusions will ultimately require daily iron chelation at a cost that is prohibitive to most families in low-income settings. One randomized controlled trial provided evidence that HU therapy may be an effective therapy for secondary prevention of strokes when compared to no therapy (Blood. 2012;119(17):3925-3932). In the SWiTCH trial, the incidence rate of stroke recurrence in the group randomly allocated to receive maximum tolerated dose HU therapy was significantly higher than the group randomly assigned to receive blood transfusion therapy (5.6 and 0 events per 100 person-years, respectively, but considerably lower when compared to children not treated with any treatment, approximately 28 events per 100 person-years (Niger Postgrad Med J. 2013;20(3):181-187). Given the practical limitations for regular blood transfusion therapy, we tested the hypothesis that for secondary stroke prevention among children with SCA and acute overt ischemic stroke, fixed moderated dose HU therapy (~20 mg/kg/day) results in 80% relative risk reduction when compared to fixed low-dose HU therapy (10 mg/kg/day) in a randomized controlled trial (SPRINT Trial; NCT02675790). Methodology In phase III controlled trial, partially blind d controlled trial, we randomly assigned children 1 - 16 years of age with SCA and a new-onset of ischemic stroke (within 1 month) to receive fixed moderate-dose HU therapy at 20 mg/kg/day or fixed-low dose HU therapy at 10 mg/kg/day) with a monthly follow-up for at least 36 months. The primary endpoint was a recurrence of overt stroke or transient ischemic attack. Myelosuppression was assessed with monthly CBCs. Adherence to hydroxyurea was based on an increase in MCV from baseline and monthly pill count return, as a percent of dispensed pills. Results A total of 101 children with SCA were randomly assigned to fixed low- (~10 mg/kg/day) or moderate- (~20 mg/kg/day) dose hydroxyurea. The mean age was 6.6 years; 55.4% were males, and the median follow up was 1.6 years (IQR 1.0 - 2.3). The DSMB stopped the trial early due to the futility of the primary endpoint. In the fixed low- and moderate-dose groups, the incidence rates of recurrent strokes per 100 person-years were 7.1 and 6.0, respectively, incidence rate ratio of 0.85 (95% CI: 0.20 - 3.34), p=0.999. The incidence rates of mortality per 100 person-years in the fixed low dose and moderate- fixed-dose groups were 2.38 and 3.63, respectively, with an incidence rate ratio of 1.53 (95% CI: 0.18 - 18.30), p=0.98. No participant had hydroxyurea therapy stopped because of myelosuppression. As a measure of adherence, MCV from baseline to endpoint increased 6.2 fl and 13.3 fl in the fixed low- and moderate-dose groups, respectively, p=0.025; returned pills during the trial were 3.3% and 3.5% in the fixed low- and moderate-dose groups, respectively, p= 0.76. Conclusion For secondary stroke prevention, in a randomized controlled trial in children with SCA and new onset of ischemic strokes, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of stroke recurrence. Fixed low-dose hydroxyurea for secondary prevention of strokes in Nigeria provided similar stroke recurrence rate, when compared to the SWiTCH Trial (Blood. 2012;119(17):3925-3932) with the maximum tolerated dose of hydroxyurea of 7.0 and 5.7 events per 100 person-years, respectively. For secondary stroke prevention, in low-income settings without access to indefinite regular blood transfusion therapy, fixed low-dose hydroxyurea of at least 10 mg/kg/day with biannual CBC is a new evidence-based strategy to prevent strokes and minimize unnecessary laboratory testing. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell

Treatment of cryptogenicstroke patients with atrial fibrillation detected by insertable cardiac monitors reduces recurrent stroke risk to background levels

Abstract Background Atrial fibrillation (AF) is a well-known risk factor for ischemic stroke with a reported increased incidence range of 2.5 to 5-fold. However, it is not well established whether treatment of cryptogenic stroke patients with AF detected by insertable cardiac monitors (ICM) reduces the risk of recurrent stroke. Objective To compare recurrent stroke rates between cryptogenic stroke patients who have AF detected by ICMs and thus started on oral anticoagulation (OAC) treatment and those without detected AF. Methods We performed a retrospective analysis of consecutive patients who received an ICM for the purpose of AF monitoring following a cryptogenic stroke between July 2015 and March 2019. Patients with prior documented AF history were excluded. We calculated the rates of AF detection and OAC initiation. We also compared recurrent stroke rates between patients with and without AF detected. Results A total of 298 cryptogenic stroke patients receiving an ICM and home remote monitoring were studied (mean age: 77 SD: 11.7; Female/Male: 147 (49%)/151; virtual CHA2DS2-VASc: 4.96 SD: 1.28). AF was newly detected in 91 (29.6%) patients over a mean follow-up of 46 months. Of these patients 68 (72.4%) were started on OAC, 12 (15.3%) were already on OAC and 11 (12.2%) remained not anticoagulated. Of the total patients evaluated, 22 patients (7.3%) developed recurrent strokes for an annualized stroke rate of 1.926%. Of those, 8 occurred among the 91 patients with newly detected AF, for an annualized stroke rate of 1.72%. The remining 14 recurrent strokes occurred among the 207 patients without AF detected, for an annualized stroke rate of 1.76%; (p=0.87). One recurrent stroke occurred in an AF patient not anticoagulated due to a prior bleeding event. No hemorrhagic strokes were reported in the AF-OAC group. Conclusion Our study found that newly AF was detected by ICM in almost 1/3 (29%) of cryptogenic stroke patients (consistent with previous studies), and the vast majority of them (88%) accordingly received oral anticoagulation. There was not a significant difference in recurrent stroke rates among patients with AF detected on OAC and those without AF detected. This suggests that rigorous arrhythmia monitoring with ICMs can help identify cryptogenic stroke patients with new AF and initiate oral anticoagulation accordingly, to reduce their risk of recurrent stroke to background levels. Annualized Stroke Risk Funding Acknowledgement Type of funding source: None

Structural and functional atrial remodelling after transcatheter closure of patent foramen ovale

Abstract Introduction Patent foramen ovale (PFO) is a common abnormality affecting more than 20% of the adult population. For most people they are accidental findings; however, in some the PFO can open widely enabling paradoxical embolisation. Randomised controlled trials have demonstrated in patients with cryptogenic stroke that transcatheter closure of PFO with a septal occluder device is associated with reduced rates of recurrent stroke. However, the impact of atrial septal closure on left atrial (LA) and right atrial (RA) structural and functional remodelling is less known. Methods We prospectively enrolled 53 patients with cryptogenic ischemic stroke and PFO eligible for transcatheter PFO closure (mean age 46±11 years, 44% females). National Institute of Health Stroke Score (NIHSS), and the modified Rankin score (mRS) were calculated as markers of clinical severity of the index stroke. Presence of any shunt, atrial volumes and functional parameters were evaluated including LA reservoir, conduit and contraction function before PFO closure and 12 months after procedure. Beyond conventional transthoracic echocardiography (Philips Epiq CVx Ultrasound), two dimensional speckle tracking method was used to assess body surface area-indexed LA maximal volume (LAVmaxi), LA minimal volume (LAVmini), LA volume before left atrial contraction (LApreAi), LA ejection fraction (LAEF), LA reservoir strain (LASres), LA conduit strain (LAScond), LA contraction strain (LAScontr), LA peak systolic strain rates (LASRs), LA peak early diastolic strain rate (LASRe) and LA peak late diastolic strain rate (LASRa) using dedicated software on separate workstation (Cardiac Performance; TomTec Imaging, Unterschleissheim, Germany). Results The index stroke was modest and non-disabling, with an NIHSS 3.37±2.63 and mRS 1.67±1.06. Baseline LA, RA volumes and dimensions were in normal range (LAVi 25.5±9.6 ml/m2; LA length 37.6±6.2 mm; LA width 40.4±7.1 mm; RA length 36.6±6.7 mm; RA width 39.5±8.6 mm). Thirty-seven patient had 12 month clinical follow-up examinations revealing no significant differences (all p values &amp;gt;0.05) in atrial volumes, ejection fraction and strain parameters. LASRa was significantly lower after 12 month (p=0.03; baseline LASRa −1.7±0.7 s–1 vs follow-up LASRa −1.3±0.9 s–1) No new cerebral ischaemic events, aortic erosions, atrial fibrillation, significant residual shunts or device thrombosis and displacement were recorded during the follow-up. Conclusion PFO-associated strokes in young individuals are mainly non-disabling. Our study suggests that transcatheter interatrial closure is effective without promoting unfavourable atrial anatomical remodelling during short-term follow-up, however, it may affect active atrial contraction. Long-term follow-up examinations are needed to investigate the potential late impact of occluders on atrial anatomical, functional remodelling. Funding Acknowledgement Type of funding source: None