Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association.

The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive low-density lipoprotein cholesterol lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke. The writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize existing evidence and to identify gaps in current knowledge. Although some retrospective, case control, and prospective longitudinal studies suggest that statins and low-density lipoprotein cholesterol lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion. The risk of a hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is nonsignificant, and achieving very low levels of low-density lipoprotein cholesterol does not increase that risk. Data reflecting the risk of hemorrhagic stroke with lipid-lowering treatment among patients with a history of hemorrhagic stroke are not robust and require additional focused study.

Optimal Randomization Designs for Large Multicenter Clinical Trials: From the National Institutes of Health Stroke Trials Network Funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke Experience.

From 2016 to 2021, the National Institutes of Health Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke initiated ten multicenter randomized controlled clinical trials. Optimal subject randomization designs are demanded with 4 critical properties: (1) protection of treatment assignment randomness, (2) achievement of the desired treatment allocation ratio, (3) balancing of baseline covariates, and (4) ease of implementation. For acute stroke trials, it is necessary to minimize the time between eligibility assessment and treatment initiation. This article reviews the randomization designs for 3 trials currently enrolling in Stroke Trials Network funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke, the SATURN (Statins in Intracerebral Hemorrhage Trial), the MOST (Multiarm Optimization of Stroke Thrombolysis Trial), and the FASTEST (Recombinant Factor VIIa for Hemorrhagic Stroke Trial). Randomization methods utilized in these trials include minimal sufficient balance, block urn design, big stick design, and step-forward randomization. Their advantages and limitations are reviewed and compared with traditional stratified permuted block design and minimization.

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Statins for the Prevention of Post-Stroke Seizure and Epilepsy Development: A Systematic Review and Meta-Analysis.

OBJECTIVES: Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. Statins have increasingly garnered attention as a potential preventive strategy due to their pleiotropic effects beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. We aim to assess the evidence on statin use for prevention of post-stroke early-onset seizures and post-stroke epilepsy. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, which was prospectively registered with PROSPERO (CRD42019144916). PubMed and Embase were searched from database inception to 05/2020 for English-language, full-text studies examining the association between statin use in adults and development of early-onset seizures (≤7 days post-stroke) or post-stroke epilepsy. Pooled analyses were based on random-effects models using the inverse-variance method. RESULTS: Of 182 citations identified, 175 were excluded due to duplication or ineligibility. The 7 eligible publications were all cohort studies from East Asia or South America, with a total of 53,579 patients. Pre-stroke statin use was not associated with post-stroke epilepsy (3 studies pooled: OR 1.14, CI 0.91-1.42). However, post-stroke statin use was associated with lower risk of both early-onset seizures (3 studies pooled: OR 0.36, CI 0.25-0.53), and post-stroke epilepsy (6 studies pooled: OR 0.64, CI 0.46-0.88). CONCLUSIONS: Review of 7 cohort studies suggested post-stroke, but not pre-stroke, statin use may be associated with reduced risk of early-onset seizures and post-stroke epilepsy. Further research is warranted to validate these findings in broader populations and better parse the temporal components of the associations.

Comparison of Automated CT Perfusion Softwares in Evaluation of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Automated imaging software is integral to decision-making in acute ischemic stroke (AIS) during extended time windows. RAPID software is the most widely used and has been validated in landmark endovascular trials. Olea software is another commercially available and FDA-approved software, but has not been studied in AIS trials. We aimed to compare the diagnostic utility and accuracy of RAPID and Olea in everyday clinical practice outside of a clinical trial. METHODS: We analyzed prospectively-collected data from a consecutive cohort of 141 patients with suspected AIS who underwent computed tomography perfusion upon presentation followed by diffusion-weighted magnetic resonance imaging (DWI-MRI) within 24-48 hours. Core infarct was defined as the region with a relative cerebral blood flow (rCBF) less than 30% on RAPID and rCBF less than 40% on Olea (default settings). We also evaluated rCBF less than 30% on Olea to match RAPID's default setting. Infarct volume on DWI-MRI was measured using a semiautomated segmentation method. RESULTS: Twenty-one patients were excluded; 14 due to poor bolus tracking and/or motion artifact, and 7 due to software failure. The software failure rate was 4.7% [6/127] with RAPID versus .78% [1/127] with Olea (P = .12). For the remaining 120 patients, the sensitivity and specificity for detecting an acute infarct were 40.5% and 97.6% for RAPID; 50.6% and 85.4% for Olea; and for detecting large infarcts (≥70 mL on DWI-MRI) 73.7% and 81.2% for RAPID; 73.7% and 68.3% for Olea. Core infarct volume on RAPID was more closely correlated with DWI-MRI infarct volume (rho = .64) than Olea (rho = .42). CONCLUSIONS: Our head-to-head comparison of these 2 commonly-used softwares in the clinical setting elucidates the pros and cons of their use to guide decision-making for AIS management in the acute setting.

Clinical Outcomes and Neuroimaging Profiles in Nondisabled Patients With Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods- Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of <2 with acute nontraumatic anticoagulant-related ICH divided into 2 groups according to the type of anticoagulant: NOAC versus VKA. We recorded baseline ICH volume, significant hematoma expansion (absolute [12.5 mL] or relative [>33%] increase), neurological severity measured by National Institutes of Health Stroke Scale score, 90-day mortality, and functional status (modified Rankin Scale score). Results- Our cohort comprised 196 patients, 62 NOAC related (mean age, 75.0±11.4 years; 54.8% men) and 134 VKA related (mean age, 72.3±10.5; 73.1% men). There were no differences in vascular comorbidities, antiplatelet, and statin use; NOAC-related ICH patients had lower median baseline hematoma volume (13.8 [2.5-37.6] versus 19.5 [6.6-52.0] mL; P=0.026) and were less likely to have severe neurological deficits (National Institutes of Health Stroke Scale score of >10 points) on admission (37% versus 55.3%, P=0.025). VKA-ICH were more likely to have significant hematoma expansion (37.4% versus 17%, P=0.008). NOAC pretreatment was independently associated with smaller baseline hematoma volume (standardized linear regression coefficient:-0.415 [95% CI, -0.780 to -0.051]) resulting in lower likelihood of severe neurological deficit (odds ratio, 0.44; 95% CI, 0.22-0.85) in multivariable-adjusted models. Conclusions- Patients with NOAC-related ICH have smaller baseline hematoma volumes and lower odds of severe neurological deficit compared with VKA-related ICH. These findings are important for practicing clinicians making anticoagulation choices.

Heme oxygenase-1-mediated neuroprotection in subarachnoid hemorrhage via intracerebroventricular deferoxamine.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating disease that affects over 30,000 Americans per year. Previous animal studies have explored the therapeutic effects of deferoxamine (DFX) via its iron-chelating properties after SAH, but none have assessed the necessity of microglial/macrophage heme oxygenase-1 (HO-1 or Hmox1) in DFX neuroprotection, nor has the efficacy of an intracerebroventricular (ICV) administration route been fully examined. We explored the therapeutic efficacy of systemic and ICV DFX in a SAH mouse model and its effect on microglial/macrophage HO-1. METHODS: Wild-type (WT) mice were split into the following treatment groups: SAH sham + vehicle, SAH + vehicle, SAH + intraperitoneal (IP) DFX, and SAH + ICV DFX. For each experimental group, neuronal damage, cognitive outcome, vasospasm, cerebral and hematogenous myeloid cell populations, cerebral IL-6 concentration, and mitochondrial superoxide anion production were measured. HO-1 co-localization to microglia was measured using confocal images. Trans-wells with WT or HO-1(-/-) microglia and hippocampal neurons were treated with vehicle, red blood cells (RBCs), or RBCs with DFX; neuronal damage, TNF-α concentration, and microglial HO-1 expression were measured. HO-1 conditional knockouts were used to study myeloid, neuronal, and astrocyte HO-1 involvement in DFX-induced neuroprotection and cognitive recovery. RESULTS: DFX treatment after SAH decreased cortical damage and improved cognitive outcome after SAH yet had no effect on vasospasm; ICV DFX was most neuroprotective. ICV DFX treatment after SAH decreased cerebral IL-6 concentration and trended towards decreased mitochondrial superoxide anion production. ICV DFX treatment after SAH effected an increase in HO-1 co-localization to microglia. DFX treatment of WT microglia with RBCs in the trans-wells showed decreased neuronal damage; this effect was abolished in HO-1(-/-) microglia. ICV DFX after SAH decreased neuronal damage and improved cognition in Hmox1 (fl/fl) control and Nes (Cre) :Hmox1 (fl/fl) mice, but not LyzM (Cre) :Hmox1 (fl/fl) mice. CONCLUSIONS: DFX neuroprotection is independent of vasospasm. ICV DFX treatment provides superior neuroprotection in a mouse model of SAH. Mechanisms of DFX neuroprotection after SAH may involve microglial/macrophage HO-1 expression. Monitoring patient HO-1 expression during DFX treatment for hemorrhagic stroke may help clinicians identify patients that are more likely to respond to treatment.

Rate of Perihematomal Edema Expansion Predicts Outcome After Intracerebral Hemorrhage.

OBJECTIVES: Intracerebral hemorrhage is a devastating disorder with no current treatment. Whether perihematomal edema is an independent predictor of neurologic outcome is controversial. We sought to determine whether perihematomal edema expansion rate predicts outcome after intracerebral hemorrhage. DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. PATIENTS: One hundred thirty-nine consecutive supratentorial spontaneous intracerebral hemorrhage patients 18 years or older admitted between 2000 and 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intracerebral hemorrhage, intraventricular hemorrhage, and perihematomal edema volumes were measured from CT scans obtained at presentation, 24-hours, and 72-hours postintracerebral hemorrhage. Perihematomal edema expansion rate was the difference between initial and follow-up perihematomal edema volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) perihematomal edema expansion rate at 24 hours and 90-day mortality and 2) perihematomal edema expansion rate at 24 hours and 90-day modified Rankin Scale score. Perihematomal edema expansion rate between admission and 24-hours postintracerebral hemorrhage was a significant predictor of 90-day mortality (odds ratio, 2.97; 95% CI, 1.48-5.99; p = 0.002). This association persisted after adjusting for all components of the intracerebral hemorrhage score (odds ratio, 2.21; 95% CI, 1.05-4.64; p = 0.04). Similarly, higher 24-hour perihematomal edema expansion rate was associated with poorer modified Rankin Scale score in an ordinal shift analysis (odds ratio, 2.40; 95% CI, 1.37-4.21; p = 0.002). The association persisted after adjustment for all intracerebral hemorrhage score components (odds ratio, 2.07; 95% CI, 1.12-3.83; p = 0.02). CONCLUSIONS: Faster perihematomal edema expansion rate 24-hours postintracerebral hemorrhage is associated with worse outcome. Perihematomal edema may represent an attractive translational target for secondary injury after intracerebral hemorrhage.

Sexual activity as a trigger for intracranial hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) has been reported in association with sexual activity. A case-series of patients with ICH following sexual activity is presented to further elucidate the role of the physiologic sexual response as a trigger of ICH. METHOD: A retrospective review of the medical record was performed, identifying patients presenting with ICH temporally related to sexual activity. Clinical and radiographic data were collected and reported. RESULTS: Sixteen patients presented with non-traumatic ICH temporally related to sexual activity. Eight (50 %) patients presented with aneurysmal subarachnoid hemorrhage, four (25 %) with angiogram-negative subarachnoid hemorrhage, two (12.5 %) with a ruptured arteriovenous malformation, and two (12.5 %) with an intracerebral basal ganglia hemorrhage. Overall average age was 49.9 (range, 28-74) years. Sexual activity involved male-female intercourse in 14 (87.5 %) patients and masturbation in 2 (12.5 %) patients. CONCLUSIONS: Sexual-activity-related ICH is rare and includes various etiologies. The human sexual response in associated with dramatic increases in arterial blood pressure, which likely underlies the association.

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage. METHODS: A formal literature search of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. RESULTS: Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated. CONCLUSIONS: Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted. These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage.

Measurement of perihematomal edema in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Perihematomal edema (PHE) is a marker of secondary injury in intracerebral hemorrhage (ICH). PHE measurement on computed tomography (CT) is challenging, and the principles used to detect PHE have not been described fully. We developed a systematic approach for CT-based measurement of PHE. METHODS: Two independent raters measured PHE volumes on baseline and 24-hour post-ICH CT scans of 20 primary supratentorial ICH subjects. Boundaries were outlined with an edge-detection tool and adjusted after inspection of the 3 orthogonal planes. PHE was delineated with the additional principle that it should be (a) more hypodense than the corresponding area in the contralateral hemisphere and (b) most hypodense immediately surrounding the hemorrhage. We examined intra- and interrater reliability using intraclass correlation coefficients and Bland-Altman plots for interrater consistency. CT-based PHE was also compared using magnetic resonance imaging-based PHE detection for 18 subjects. RESULTS: Median PHE volumes were 22.7 cc at baseline and 20.4 cc at 24 hours post-ICH. There were no statistically significant differences in PHE measurements between raters. Interrater and intrarater reliability for PHE were excellent. At baseline and 24 hours, interrater intraclass correlation coefficients were 0.98 (0.96-1.00) and 0.98 (0.97-1.00); intrarater intraclass correlation coefficients were 0.99 (0.99-1.00) and 0.99 (0.98-1.00). Bland-Altman analysis showed the bias for PHE measurements at baseline and 24 hours, -0.5 cc (SD, 5.4) and -3.2 cc (SD, 5.0), was acceptably small. PHE volumes determined by CT and magnetic resonance imaging were similar (23.9±16.9 cc versus 23.9±16.0 cc, R(2) = 0.98, P<0.0001). CONCLUSIONS: Our method measures PHE with excellent reliability at baseline and 24 hours post-ICH.

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis.

IMPORTANCE: Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. OBJECTIVE: To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES: We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION: Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS: Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES: Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS: Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE: Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

A comparative study of fractional anisotropy measures and ICH score in predicting functional outcomes after intracerebral hemorrhage.

BACKGROUND: Improved prognostication during the acute phase of intracerebral hemorrhage (ICH) could influence goals of care. We investigated the utility of diffusion tensor imaging (DTI)-derived data obtained during the acute phase of ICH in predicting outcome, compared with the ICH score. METHODS: We measured fractional anisotropy (FA) values in 5 slices below the level of the lesion on the affected and unaffected corticospinal tracts (CST) and in the cerebral peduncles (CPs) in 32 patients with supratentorial ICH who had DTI MRI within 4 days after ictus. We calculated the FA ratio (rFA = FAaffected side/FAunaffected side), and examined the value of the ICH score and rFA in predicting functional outcome assessed by modified Ranking Scale (mRS) at follow-up, using ROC analyses. RESULTS: The rFA values at the CPs level, but not the 5 slices below the lesion, were significantly lower in the group with poor functional outcome (defined as mRS > 2) than in those with good functional outcome (0.96 ± 0.14 vs. 0.99 ± 0.08, p = 0.025). The ICH score had greater areas under ROC curve in predicting functional outcome compared to the mean rFA (AUC 0.74 vs. 0.44; p = 0.01 for mRS > 2; and 0.84 vs. 0.40; p < 0.001 for mRS > 3). CONCLUSIONS: The prognostic value of the ICH score surpassed that of DTI-derived data during the acute phase of ICH in this cohort of patients. Prospective and larger studies are needed to validate our findings and to assess the prognostic role of various DTI-derived measures at different times following ICH.

Left atrial appendage closure in patients with atrial fibrillation and acute ischaemic stroke despite anticoagulation.

BACKGROUND: The occurrence of acute ischaemic stroke (AIS) while using oral anticoagulants (OAC) is an increasingly recognised problem among nonvalvular atrial fibrillation (NVAF) patients. We aimed to elucidate the potential role of left atrial appendage closure (LAAC) for stroke prevention in patients with AIS despite OAC use (AIS-despite-OAC). METHODS: We retrospectively collected baseline and follow-up data from consecutive NVAF patients who had AIS-despite-OAC and subsequently underwent endovascular LAAC, between January 2015 and October 2021. The primary outcome measure was the occurrence of AIS after LAAC, and the safety outcome was symptomatic intracerebral haemorrhage (ICH). RESULTS: 29 patients had LAAC specifically because of AIS-despite-OAC. The mean age at the time of the procedure was 73.4±8.7, 13 were female (44.82%). The mean CHA2DS2-VASc score was 5.96±1.32, with an expected AIS risk of 8.44 per 100 patient-years. 14 patients (48%) had two or more past AIS-despite-OAC. After LAAC, 27 patients (93.10%) were discharged on OAC which was discontinued in 17 (58.62%) after transoesophageal echocardiogram at 6 weeks. Over a mean of 1.75±1.0 years follow-up after LAAC, one patient had an AIS (incidence rate (IR) 1.97 per 100 patient-years). One patient with severe cerebral microangiopathy had a small ICH while on direct OAC and antiplatelet 647 days after LAAC. CONCLUSIONS: LAAC in AIS-despite-OAC patients demonstrated a low annual AIS recurrence rate in our cohort (1.97%) compared with the expected IR based on their CHA2DS2-VASc scores (8.44%) and to recent large series of AIS-despite-OAC patients treated with OAC/aspirin only (5.3%-8.9%). These hypothesis-generating findings support randomised trials of LAAC in AIS-despite-OAC patients.

Safety and efficacy of remote ischemic conditioning for spontaneous intracerebral hemorrhage (SERIC-ICH): A multicenter, randomized, parallel-controlled clinical trial study design and protocol.

BACKGROUND: Previous studies have revealed that remote ischemic conditioning (RIC) may have a neuroprotective function. However, the potential benefit of RIC for patients with ICH remain unclear. OBJECTIVE: The primary aim of this study is to assess the safety and efficacy of RIC for patients with ICH. METHODS: The Safety and Efficacy of RIC for Spontaneous ICH (SERIC-ICH) is an ongoing prospective, randomized, multicenter, parallel-controlled, and blinded-endpoint clinical trial. The study will enroll an estimated 2000 patients aged ⩾18 years within 24 h after ICH onset, with National Institutes of Health Stroke Scale ⩾6 and Glasgow Coma Scale ⩾8 upon presentation. The patients will be randomly assigned to the RIC or control groups (1:1) and will be treated with cuffs inflated to a pressure of 200 or 60 mmHg, respectively, twice daily for 7 days. Each RIC treatment will consist of four cycles of arm ischemia for 5 min, followed by reperfusion for another 5 min, for a total procedure time of 35 min. The primary efficacy outcome measure is the proportion of patients with good functional outcomes (modified Rankin scale 0-2) at 180 days. The safety outcome measures will include all adverse events and severe adverse events occurring in the course of the study. DISCUSSION: RIC is an inexpensive intervention and might be a strategy to improve outcomes in patients with ICH. The SERIC-ICH trial will investigate whether RIC treatment can be applied as an adjuvant treatment in the acute phase of ICH and identify safety issues.