Therapy For Secondary Stroke Prevention Research Articles

Anticoagulation vs Antiplatelets Across Subgroups of Embolic Stroke of Undetermined Source: A Meta-Analysis of Randomized Controlled Trials.

The term "embolic stroke of undetermined source" (ESUS) encompasses a substantial but heterogeneous population of patients with ischemic stroke, underscoring the importance of identifying personalized treatment strategies. In subgroups of patients randomized in ESUS trials, we evaluated the effectiveness of anticoagulation compared with antiplatelet therapy in secondary ischemic stroke prevention. A study-level meta-analysis was conducted on randomized controlled trials of patients with ESUS, comparing anticoagulation with antiplatelet therapy. The primary efficacy outcome was recurrent ischemic stroke, and safety outcomes were major bleeding and death. Subgroups assessed were age, sex, presence of patent foramen ovale (PFO), left atrial enlargement (LAE), and atrial cardiopathy. Pooled risk ratios (RRs) were meta-analyzed. Cochrane Risk of Bias Tool 2.0 was used for risk-of-bias assessment. A total of 7 randomized controlled trials involving 14,804 patients were analyzed, with 7,406 patients treated with anticoagulation and 7,398 treated with antiplatelet therapy. Compared with antiplatelet therapy, anticoagulation was associated with a similar rate of recurrent ischemic stroke (RR 0.91, 95% CI 0.80-1.05; I2 = 0%). In ESUS with PFO, anticoagulation was associated with significantly lower risk of ischemic stroke (RR 0.59, 95% CI 0.35-0.98; I2 = 0%). Heterogeneity was present in those with LAE: antiplatelet therapy was superior in trials allowing cardiac monitoring after randomization (RR 6.65, 95% CI 1.26-35.08; I2 = 0%), but anticoagulation was superior in trials prohibiting cardiac monitoring after randomization (RR 0.25 95% CI 0.07-0.89). Subgroups based on age, sex, or presence of atrial cardiopathy did not benefit from anticoagulation over antiplatelet therapy. In this meta-analysis, an empiric anticoagulation approach is not beneficial for patients with ESUS. This finding highlights the importance of an individualized treatment strategy. Such a strategy should include prolonged cardiac monitoring for atrial fibrillation, particularly in patients with moderate-to-severe LAE. Anticoagulation treatment showed promise in patients with medically treated PFO. Other subgroups did not benefit from anticoagulation therapy. Large prospective studies within ESUS subgroups are needed to validate our findings.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy

Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. ClinicalTrials.gov Identifier: NCT03192215.

Abstract WP238: Efficacy of Dual Antiplatelet Therapy After Lacunar versus Non-Lacunar Syndromes in the POINT Trial

Introduction: About 20% of ischemic strokes are lacunar infarcts, the pathophysiology of which differs from that of other stroke etiological subtypes. The POINT trial demonstrated the efficacy of dual antiplatelet therapy (DAPT) for secondary stroke prevention in patients with minor ischemic stroke and high-risk TIA, but it remains unknown whether this benefit differed in lacunar versus non-lacunar strokes. Method: In a secondary analysis of POINT trial data, we compared the efficacy of DAPT in patients with an index lacunar syndrome versus not. A lacunar syndrome was defined based on common classic lacunar syndromes (e.g., pure motor hemiparesis, clumsy-hand dysarthria) and ascertained using subcomponents of the National Institutes of Health Stroke Scale documented at baseline. Our primary efficacy outcome was ischemic stroke and the safety outcome was intracranial hemorrhage. We used survival analysis and tests of interaction to compare the effect of DAPT between the lacunar and non-lacunar subgroups. Result: Among 4,881 patients enrolled in the study, 1,083 (22.1%) were classified as having an index lacunar syndrome. The effect of DAPT on the risk of ischemic stroke did not vary significantly after a lacunar syndrome (HR, 0.76; 95% CI, 0.52-1.09) versus after a non-lacunar syndrome (HR, 0.69; 95% CI, 0.50-0.95) (P value for interaction, 0.70). Similarly, the effect of DAPT on the risk of intracranial hemorrhage did not vary significantly after a lacunar syndrome (HR, 2.82; 95% CI, 0.29-27.1) versus after a non-lacunar syndrome (HR, 2.10; 95% CI, 0.63-6.99) (P for interaction, 0.82). Conclusion: In a post hoc secondary analysis of the POINT trial, we found no evidence of a lesser benefit of DAPT after a minor ischemic stroke or TIA in patients presenting with a lacunar syndrome compared to other stroke subtypes.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.

The Optimal Threshold for Hemoglobin S Percent Level While Performing Regular Blood Transfusion Therapy to Prevent Severe Vaso-Occlusive Pain Events in Children with Sickle Cell Anemia: A Secondary Data Analysis of Participants in the SIT Trial

Introduction: Children with sickle cell disease (SCD) often experience frequent severe acute vaso-occlusive pain events, unresponsive to FDA-approved therapies (hydroxyurea, L-glutamine, crizanlizumab) to decrease the severe acute vaso-occlusive pain event incidence rate. The ASH guidelines for pain management recommend regular blood transfusion therapy after FDA-approved therapies have failed to decrease the high rate of severe acute vaso-occlusive pain events ( The Journal of Pediatrics, 139(6), 785-789). However, unlike regular blood transfusion therapy for primary and secondary stroke prevention, for which the goal hemoglobin S (Hb S) level is ≤ 30% , no optimal Hb S threshold has been established to attenuate the severe acute vaso-occlusive pain event incidence rate. We tested the hypothesis that among children receiving regular blood transfusion therapy with a goal to keep the mean hemoglobin S level < 30%, participants that achieved a mean Hb S level < 30% would have lower rates of severe acute vaso-occlusive pain events requiring hospitalization than children regularly transfused with mean Hb S level > 30%. Evidence to support our hypothesis would provide the first evidence-based guidelines for the optimal hemoglobin S threshold to decrease the acute vaso-occlusive pain event incidence rate in children with sickle cell anemia (HbSS). Methods: The SIT trial was a single-blind clinical trial( Blood Advances, 4(12), 2656-2701), where participants were children with sickle cell anemia randomly allocated to receive regular blood transfusion therapy (transfusion group) or standard care (observation group). Participants receiving regular blood transfusion therapy from the SIT Trial were included in the secondary analysis. Eligibility criteria include participants between 5 and 15 years of age, with no history of stroke, one or more silent cerebral infarcts on magnetic resonance imaging, and a neurologic examination showing no abnormalities. The transfusion therapy goal was to keep the maximum Hb S level < 30%. For the ancillary study, participants were included only in the transfusion arm of the trial. The primary endpoint of this ancillary study was the incidence rate of hospitalization for vaso-occlusive pain episodes among those receiving only regular blood transfusion therapy. We conducted a zero-inflated negative binomial regression analysis to determine the association between the incidence rate for severe acute vaso-occlusive pain events requiring hospitalization and independent covariates, including age at the time of random allocation, sex, and mean hemoglobin S level (< 30% and > 30%). Results: A total of 90 participants received regular blood transfusion therapy in the SIT trial. Among participants transfused, 53 and 37 individuals had a mean Hb S level of < 30% and > 30%, respectively. The median time on transfusions for the groups with Hb S levels of < 30% and > 30% was 2.9 years for both groups. Among the participants, 10.8% (4/37) who had a mean Hb S < 30% and 20.8% (11/53) of those with a mean Hb S > 30% experienced at least one hospitalization for a severe acute vaso-occlusive pain event. The mean hemoglobin S levels in the < 30% and > 30% groups were 25.4% and 37.5%, respectively. The mean hospital rates for severe acute vaso-occlusive pain events in the two groups < 30% and >30% were 9.4 (95% confidence interval 9.4 - 17.2 person-years) and 29.2 per 100 person-years (95% confidence interval, 21.0 - 39.5 person-years), respectively, P = 0.078. In the multivariable analysis, the incidence rate ratio for severe acute vaso-occlusive pain events showed that there was no statistical difference between those with a mean Hb S level in groups < 30% and > 30%, 0.65; P=0.43. Children with a higher baseline hemoglobin level were more likely to achieve a mean hemoglobin S level < 30%. Conclusion: In children with sickle cell anemia, receiving regular blood transfusion therapy with the goal of keeping the mean hemoglobin S level < 30%, achieving a mean hemoglobin S level > 30% was as effective as a mean hemoglobin S level < 30 % in decreasing the incidence rate of severe acute vaso-occlusive pain events requiring hospitalization. Further studies are warranted to identify reliable measures of the efficacy of regular blood transfusion therapy for the reduction of acute vaso-occlusive pain events.

Sex Difference in the Impact of Dual Antiplatelet Therapy using Cilostazol for Secondary Stroke Prevention: A Sub-Analysis of CSPS.com.

Although some sex differences in stroke have been reported, differences in the effects of antiplatelet therapy for secondary stroke prevention have not been clarified. In the Cilostazol Stroke Prevention Study combination trial, patients with high-risk, non-cardioembolic ischemic stroke between 8 and 180 days after onset treated with aspirin or clopidogrel alone were recruited and randomly assigned to receive either monotherapy or dual antiplatelet therapy (DAPT) using cilostazol and followed up for 0.5-3.5 years. The primary efficacy outcome was recurrence of ischemic stroke. The safety outcome was severe or life-threatening hemorrhage. Outcomes were analyzed by sex. A total of 1,320 male patients and 558 female patients were included. The male patients had more risk factors than the female patients. In male patients, the primary endpoint occurred at a rate of 2.0 per 100-patient years in the DAPT group and 5.1 per 100 patient-years in the monotherapy group (hazard ratio (HR), 0.40; 95% confidence interval (CI), 0.23-0.68). In male patients, DAPT prolonged the time to recurrent stroke by 4.02-fold (95% CI, 1.63-9.96) compared with monotherapy. In female patients, the average annual event rates were 2.7 per 100 patient-years in the DAPT group and 3.3 per 100 patient-years in the monotherapy group (HR, 0.82; 95% CI, 0.37-1.84). Safety outcomes did not differ significantly in both male and female patients. Long-term DAPT using cilostazol reduced the recurrence of ischemic stroke and prolonged the recurrence-free time in male patients, but not in female patients.

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.

The great masquerader: recurrent ischemic strokes secondary to meningo-vascular syphilis in a 62-year-old patient with stroke risk factors (P12-5.019)

<h3>Objective:</h3> N/A <h3>Background:</h3> Syphilis is a debilitating multisystem disease resulting from infection with the spirochete Treponema pallidum. Even though it is uncommon, it is a great mimic of stroke and is misdiagnosed almost 80% of the time. It commonly involves the middle cerebral artery and basilar or anterior spinal artery territories. 4% of patients with recurrent strokes can have syphilis. We present a patient with a recurrent stroke due to meningo-vascular syphilis (MVS). <h3>Design/Methods:</h3> A 62-year-old male with hypertension, hyperlipidemia, diabetes, and coronary artery disease presented with confusion and word-finding difficulty, and was found to have an acute ischemic stroke in the right basal ganglia (BG). The patient was discharged on dual anti-platelet therapy and statin for secondary stroke prevention. As a part of the stroke workup, he was found to be highly reactive for rapid plasma regain, and the subsequent fluorescent treponemal antibody absorption test was reactive with the diagnosis of syphilis. He presented again 3 weeks later with transient facial paralysis. The cerebrospinal fluid was positive for a Venereal Disease Research Laboratory test, indicative of MVS. He received 4 million units of penicillin every 4 hours intravenously for 14 days with improvement in symptoms and no further recurrence of strokes. <h3>Results:</h3> N/A <h3>Conclusions:</h3> Our patient presented with acute ischemic infarct in BG, etiology thought to be small vessel disease in the setting of multiple stroke risk factors. Meningo-vascular syphilis, a subtype of neurosyphilis, can cause recurrent ischemic strokes. While uncommon, neurosyphilis remains prevalent in the United States and is often misdiagnosed because of its heterogenous clinical features. Syphilis screening is usually considered in young patients with a prior documented history of sexually transmitted disease however it is prudent that patients with recurrent strokes might benefit from routine screening tests for syphilis, regardless of age group or the presence of stroke risk factors. <b>Disclosure:</b> Dr. Waheed has nothing to disclose. Dr. Carranza-Renteria has nothing to disclose. Dr. Yousuf has nothing to disclose.

Follow-up Imaging After Thrombolysis: FIAT, A Randomized Trial

Current protocols for treatment of acute ischemic stroke with intravenous thrombolytics, such as alteplase (tPA) and tenecteplase (tNK), recommend the completion of a routine non-contrast head CT at 24 hours post treatment to evaluate for hemorrhage prior to the initiation of antiplatelet therapy for secondary stroke prevention. This guideline was instituted because it had been part of the protocol in the NINDS multicenter randomized placebo-controlled trial that showed the benefit of IV thrombolytics within 3 hours of stroke onset. Recent observational studies indicate that the repeat (stability) head CT rarely alters clinical management, in the absence of neurological worsening or evidence of clinical signs of hemorrhagic conversion, such as seizures, severe headache, or novel acute deficits. A solitary CT carries with it a non-negligible dose of radiation with additive cost to the medical system at large. We aimed to identify, with a randomized, blinded outcome assessment trial, if a routine head CT at 24 hours, in the absence of clinical indication, negatively influences clinical outcomes. We enrolled 58 patients, and evaluated differences between groups with t-tests. We also evaluated differences between outcomes (90 day modified Rankin Scale, mRS and change in National Institutes of Health Stroke Scale, NIHSS) from pretreatment to discharge using multivariable logistic regression, including age, baseline NIHSS, and group as independent variables. We found no added benefit of routine CT on either outcome measure. It is likely safe to forgo follow up imaging after thrombolysis in the absence of clinical decompensation.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Anticoagulant therapy in secondary stroke prevention in patients with atrial fibrillation

Anticoagulant therapy in secondary stroke prevention in patients with atrial fibrillation

Longitudinal Outcomes of Chronically Transfused Adults with Sickle Cell Anemia and a History of Childhood Stroke

Background: Rigorous studies define the use of chronic transfusion therapy (CTT) for secondary stroke prevention in children with sickle cell anemia (SCA). Limited evidence informs the use of indefinite CTT for children with SCA and a history of stroke when they enter adult care. Often, adults with a history of childhood stroke are treated by extrapolation of pediatric practice and continue CTT. However, the risk of recurrent stroke in these adults is unknown. In this retrospective study, we describe outcomes of adults with a history of SCA and childhood stroke and compare them to adults without a history of childhood stroke. Methods: The Johns Hopkins University Institutional Review Board approved this study. The inclusion criteria were: SCA diagnosis, ≥ 18 years old, received adult care at Johns Hopkins Hospital (JHH), and documentation of a stroke via diagnosis code or mention in hematology clinic notes prior to the age of 18 or no stroke in childhood. Subjects without a history of stroke in childhood were matched based on age, gender, and genotype. For each subject, we performed a systematic chart review extending from their initial encounter with hematology care at JHH (pediatric or adult, whichever was available) to the final visit in the electronic medical record. Data collection spanned from January 1990 to February 2022. Variables collected include demographic data, SCA morbidities, and CTT treatments. We reported descriptive statistics for the subjects with a history of childhood stroke. Then we compared subjects with and without childhood stroke using the Mann Whitney U test for continuous outcomes and Fischer's exact test for categorical outcomes. We performed data analysis with Stata/SE Version 16.1. Results: There were 42 subjects with SCA and a history of childhood stroke (Table 1). In this group, the median age at the time of the study was 30 years (IQR 24 to 35 years). The median age at the time of childhood stroke was 7 years (IQR 5 to 11 years), and all subjects received CTT for secondary stroke prevention. Subjects received a median of 17.7 years of CTT (IQR 12.2 to 23.3 years). The median annual pretransfusion hemoglobin S for this group was 31% (IQR 24 to 39%), which suggests adherence to CTT. The median ferritin was 3842 ng/dL (SD 3842); 45% were alloimmunized. Five subjects with a history of childhood stroke had a stroke in adulthood: one subject (age 24) had discontinued CTT, two subjects (age 21, 23) were intermittently adherent to CTT and stroke occurred at a hemoglobin S of 49% in one subject (other unrecorded), and two subjects (ages 21, 22) received regular CTT and presented with a hemoglobin S of 14% and 24% respectively. Comparison of subjects with and without a history of childhood stroke are shown (Table 2). More subjects with a history of childhood stroke received CTT than those without (33 (100%) vs 21 (63%), p = 0.0001). We observed 0.7 strokes per 100 person·years in subjects with a history of childhood stroke and 1.1 strokes per 100 person·years in subjects without a history of childhood stroke. These were not different (p = 0.63). A comparison of SCD complications between those with and without a history of childhood stroke identified that adults on CTT because of childhood stroke had less avascular necrosis (AVN) (4 (12%) vs 12 (42%), p = 0.01) and leg ulcers (0 vs. 6 (18%), p = 0.02) than those without a history of childhood stroke. Conclusions: Among 42 adults with a history of childhood stroke, recurrent strokes occurred in 12% and in a comparable number of adults without a history of childhood stroke. This finding suggests that continuing CTT in adult care may reduce the risk of recurrent stroke to that of a population without a history of childhood stroke. Here, we find that adults with a history of childhood stroke on CTT have lower rates of AVN and leg ulcers, which suggests that CTT may reduce the risk of developing these complications. Larger, prospective studies are needed to define the extent to which CTT reduces recurrent stroke in adults with a history of childhood stroke. This evidence is necessary to inform decisions to continue CTT in adulthood because iron overload associated with CTT can be morbid and the burden of CTT visits may lead to missed work, lost wages, and childcare challenges. Further studies may also enhance decisions during pediatric care to direct children with history of stroke towards curative therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Females are less likely to receive best medical therapy for stroke prevention before and after carotid revascularization than males

BackgroundCurrent professional guidelines recommend best medical therapy (BMT) with statin agents and antiplatelet therapy for primary and secondary stroke prevention in patients with carotid artery stenosis. We aimed to assess the association of patient sex with preoperative BMT in patients undergoing carotid revascularization. MethodsWe performed a retrospective review of Vascular Quality Initiative patients who underwent carotid endarterectomy or carotid artery stenting between January 2003 and February 2022. Multivariable logistic regression models were used to assess the association of patient sex with preoperative BMT after adjusting for sociodemographic, comorbidity, and disease severity characteristics. In-hospital outcomes were assessed by sex and preoperative BMT status. ResultsOf 214,008 patients who underwent carotid revascularization, 38.7% (n = 82,855) were female and 61.3% (n = 131,153) were male. Overall, 77.2% (n = 63,922) of females were on preoperative BMT, compared with 80.4% (n = 105,375) of males (P < .001). After adjusting for baseline differences, females had 11% lower odds of being on BMT compared with males (adjusted odds ratio, 0.89; 95% confidence interval, 0.86-0.91). Postoperatively, females had 18% lower odds of being prescribed BMT than males (adjusted odds ratio, 0.82; 95% confidence interval, 0.79-0.84). In-hospital stroke (1.20% vs 1.51%), death (0.37% vs 0.66%), and stroke/death (1.46% vs 1.98%) were all significantly lower for patients on BMT (all P < .001). ConclusionsThere is a significant discrepancy in the proportion of females versus males receiving preoperative BMT for stroke prevention before carotid artery revascularization. In-hospital outcomes are worse in patients without BMT, highlighting the importance of raising awareness and implementing targeted interventions to improve preoperative adherence to stroke prevention guidelines.

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

Abstract Introduction 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 in patients that suffer from thrombo-embolic events under OAC. 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. Purpose To compare percutaneous LAAO to standard-of-care including continuing/switching anticoagulation therapy for secondary stroke prevention in patients with AF and a prior thrombo-embolic event and/or LAA thrombus under OAC therapy. Methods The STR-OAC LAAO cohort is an international collaboration combining a selection of patients from multiple LAAO registries (22 participating centers). Patients that underwent percutaneous LAAO because of a thrombo-embolic event and/or LAA thrombus on OAC were included. Propensity score matching (optimal matching method, 1:1 ratio) with a previously published multi-center dataset of patients continuing/switching anticoagulation treatment after a thrombo-embolic event was performed to adjust for imbalances in age, sex, hypertension, diabetes mellitus and CHA2DS2-VASc score. The primary outcome was ischemic stroke. Time-to-event analysis was performed with Kaplan-Meier curves and Cox-proportional-hazard regression analyses. Results A total of 404 patients underwent LAAO between 2010–2021 and were included in the STR-OAC LAAO cohort. Mean age was 72±9 years; 44% was female and mean CHA2DS2-VASc and HAS-BLED score were 4.8±1.7 and 2.5±1.4, respectively. Most patients received a Watchman or Amplatzer device (53% and 43%). Oral anticoagulation was discontinued after LAAO at discharge or after confirmation of adequate LAA closure at 1–3 months follow-up in 44% or 20%, respectively. The remaining 35% of patients continued OAC after LAAO as an adjunctive strategy. All LAAO patients were propensity-score matched and included in the primary outcome analysis. Baseline characteristics were well balanced after matching (Table 1). During follow up including 1406 patient-years (LAAO 1007; control 399) a total of 61 patients experienced an ischemic stroke: 2.2% per patient-year in LAAO group versus 9.8% per patient-year in the control group. LAAO was associated with a significantly lower risk of ischemic stroke (HR 0.33, 95% CI [0.19–0.59], p&amp;lt;0.001) compared to standard-of-care (Figure 1). Conclusion 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. Funding Acknowledgement Type of funding sources: None.

A Challenging Case of Cerebral Amyloid Angiopathy-related Inflammation (CAAri): Implications for Secondary Stroke Prevention and Immunomodulation Therapies (P1-10.002)

A Challenging Case of Cerebral Amyloid Angiopathy-related Inflammation (CAAri): Implications for Secondary Stroke Prevention and Immunomodulation Therapies (P1-10.002)

Hemichorea as initial presentation of newly diagnosed diabetes and acute lacunar stroke

Hemichorea is one of the spectrums of involuntary, continuous, non-purposeful movement of one side of the body, a choreiform disorder. Hemichorea causes vary and include various inherited or acquired systemic conditions. There might be overlapping pathophysiology where the synergistic effects of uncontrolled hyperglycemia and vascular insufficiency cause an incomplete transient dysfunction of the striatum, leading to hemichorea. We herein describe a patient who presented with hemichorea triggered by hyperglycemia and was incidentally found to have an acute lacunar stroke. She was initiated on insulin with good glycemic control. Secondary stroke prevention therapy with aspirin and statin was also started. Her symptoms improved inpatient after stable glycemic control was achieved. After 3 months, her symptoms had completely resolved. Hemichorea is an unusual initial presentation for newly diagnosed diabetes mellitus or stroke. Hence, recognizing and diagnosing this uncommon disease entity is pertinent to make a timely and accurate diagnosis, which can lead to a rapid clinical response.

Oral anticoagulation versus antiplatelet therapy for secondary stroke prevention in patients with embolic stroke of undetermined source: A systematic review and meta-analysis.

PurposeWe performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of direct oral anticoagulation (DOAC) compared with antiplatelet therapy for secondary stroke prevention in adult patients with embolic stroke of undetermined source (ESUS).MethodWe searched major databases (Embase, MEDLINE, CINAHL, CENTRAL, and Web of Science) for RCTs published until March 2021. The primary outcome was recurrent stroke, and the main safety outcomes were major bleeding and clinically relevant non-major bleeding (CRNB). We assessed risk of bias using the Cochrane Risk of Bias tool. We used a random-effects model to determine pooled risk ratios and 95% confidence intervals in the datasets and key subgroups.FindingsOur search identified two RCTs, involving a total of 12,603 patients with ESUS. Anticoagulation with dabigatran or rivaroxaban compared with aspirin did not reduce the risk of recurrent stroke (RR, 0.96 [0.76–1.20]) or increase major bleeding (RR, 1.77 [0.80–3.89]) but significantly increased the composite of major or clinically relevant non-major bleeding (RR, 1.57 [1.26–1.97]). Prespecified subgroup analysis demonstrated consistent results according to age and sex. Additional post-hoc subgroup analyses demonstrated consistent results according to prior stroke and presence of a patent foramen ovale but suggested that DOACs reduced recurrent stroke in patients with an estimated glomerular filtration rate (eGFR) <50 and 50-80 ml/min but not in those with eGFR >80 ml/min (interaction P = 0.0234).Discussion/conclusionDirect oral anticoagulations are not more effective than aspirin in preventing stroke recurrence in patients with ESUS and increase bleeding.RegistrationPROSPERO ID: CRD42019138593

Abstract TP204: Discharge Statin Practices For Young Stroke Patients In A Stroke Clinical Network

Background: Despite the association of statin use and lowered recurrent stroke and mortality, some studies suggest young stroke patients do not receive the same intense targeted treatment medical therapies for secondary stroke prevention as older patients. Our specific objective was to determine if there were differences in statin medication discharge practices provided to young ischemic stroke patients within a Stroke Clinical Network. The Stroke Clinical Network consists of nine stroke centers located in rural, suburban and urban geographical regions. Methods: The GWTG registry was queried (FY 2017-2021) to identify ischemic stroke patients to determine statin discharge practices using the following criteria: sex, race, age groups ≥18-39 and ≥40-49, LDL levels &lt; 100, 101-129 and &gt; 130, diabetes, HTN, and smoking status. Chi squared tests of proportions were used to evaluate significant relationships between subgroups. Results: Among 1,294 young ischemic stroke patients: 53% (682/1294) were Black and 38% (493/1294) White; mean age 40.9 years (SD +/-7.21years). Men, blacks, patients older than 40 and diabetics were more likely to be discharged on a statin. There was a direct correlation between sex, race, age, LDL level and diabetes with statin discharge practices. There was no difference in statin discharge practices between smokers and nonsmokers. Conclusions: Opportunities to improve compliance with obtaining LDL levels upon admission and prescribing statins at discharge exist. Increasing statin administration in the young stroke patient population reflects best practice and will decrease mortality and morbidity.

Hemorrhagic transformation and stroke recurrence in children with cardiac disease receiving antithrombotic therapy for secondary stroke prevention

BackgroundAntithrombotic therapy is currently recommended for stroke prevention in pediatric cardioembolic stroke where the recurrence risk is high; however, safety concerns remain. The primary objective of this study was to evaluate clinical and radiographic predictors of hemorrhagic transformation and stroke recurrence in children with cardiac disease to ascertain the safety and failure rates for secondary stroke prevention. MethodsThis was a single‐center, retrospective analysis of a prospectively enrolled cohort of children with radiologically confirmed cardioembolic stroke from January 2003 to December 2017 treated with institutional guidelines. ResultsEighty‐two children met inclusion criteria (male 44 [54%]; neonates 23 [28%]; median age 0.43 years [0.08–4.23]). Hemorrhagic transformation occurred in 20 (24%) with the majority (75% of 20) being petechial and asymptomatic. One death (1%) was reported from hemorrhagic transformation. Four children (5%) had major extracranial hemorrhage. Most (95%) received antithrombic therapy, with anticoagulation being favored (82%). Greater stroke volume was associated with hemorrhagic transformation using the pediatric Alberta Stroke Program Early CT Score (6.1 ± 3.3 vs. 3.5 ± 2.3; p = .006). Stroke recurred in 11 (13%) children at a median 32 days (5.5–93) from the index event and the majority (90%) were on treatment at the time of recurrence. Children with univentricular physiology were less likely to have hemorrhagic transformation (RR 0.31; 95% CI 0.09–0.96, p = .04); however, they had higher rates of recurrent stroke before final palliative repair. ConclusionsIn spite of the 24% hemorrhagic transformation rate, antithrombotic therapy has a positive risk‐balance in certain cardioembolic stroke subgroups, particularly in those with single‐ventricle physiology, when accounting for stroke volume.

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial

The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.