Cerebral Protection in Trans-Catheter Aortic Valve Replacement: Review and Contemporary Assessment of Randomized Trial Data.

As the population has aged and as aortic valve therapies have evolved, the use of trans-catheter aortic valve replacement (TAVR) has grown dramatically over the past decade. A well-known complication of percutaneous cardiac intervention is embolic phenomena, and TAVR is among the highest risk procedures for clinical and subclinical stroke. As indications for TAVR expand to lower-risk and ultimately younger patients, the long-term consequences of stroke are amplified. Cerebral embolic protection (CEP) devices have taken a on unique preventative role following the Food and Drug Administration approval of the SentinelTM Cerebral Protection System (CPS). More recently, the PROTECTED TAVR study has spurred extensive debate in the neuro-cardiac community. In this review we describe the contemporary literature regarding stroke risk associated with TAVR, the history and role of CEP devices, a PROTECTED TAVR sub-group analysis, and implications for next steps in the field. Lastly, we explore the unique need for CEP in a younger TAVR population, as well as directions for future research.

Late device-related thrombus associated with occult malignancy years after left atrial appendage closure.

INTRODUCTION: The use of Left Atrial Appendage (LAA) occluder devices has been on the rise in patients with atrial fibrillation. Studies regarding the long-term risks of occluder devices remain sparse. MATERIALS & METHODS: In this brief report, we discuss the unusual case of an 85-year-old female with long-term complication from Left Atrial Appendage (LAA) closure: Device-Related Thrombus (DRT) about two years after insertion. RESULTS: Compared to the expected stroke rate without anticoagulation, patients with DRT on their LAAO device still had a 28 % relative reduction in ischemic stroke. This suggests that these strokes may have emanated from alternate etiologies other than the DRT. CONCLUSIONS: Patients with active or known history of cancer appears to have a higher risk of DRT. More data is needed on this topic to augment awareness and understanding of LAAO complications and DRT management strategies.

Minimally invasive epicardial surgical left atrial appendage exclusion for atrial fibrillation patients at high risk for stroke and for bleeding.

BACKGROUND: Atrial fibrillation (AF) patients at high risk for stroke and for bleeding may be unsuitable for either oral anticoagulation or endocardial left atrial appendage (LAA) occlusion. However, minimally invasive, epicardial left atrial appendage exclusion (LAAE) may be an option. OBJECTIVE: The purpose of this study was to evaluate outcomes of LAAE in high-risk AF patients not receiving oral anticoagulation. METHODS: A retrospective analysis of Medicare claims data was conducted to evaluate thromboembolic events in AF patients who underwent LAAE compared to a 1:4 propensity score-matched group of patients who did not receive LAAE (control). Neither group was receiving any oral anticoagulation at baseline or follow-up. Fine-Gray models estimated hazard ratios and evaluated between-group differences. Bootstrapping was applied to generate 95% confidence intervals (CIs). RESULTS: The LAAE group (n = 243) was 61% male (mean age 75 years). AF was nonparoxysmal in 70% (mean CHA2DS2-VASc score 5.4; mean HAS-BLED score 4.2). The matched control group (n = 972) had statistically similar characteristics. One-year adjusted estimates of thromboembolic events were 7.3% (95% CI 4.3%-11.1%) in the LAAE group and 12.1% (95% CI 9.5%-14.8%) in the control group. Absolute risk reduction was 4.8% (95% CI 0.6%-8.9%; P = .028). Adjusted hazard ratio for thromboembolic events for LAAE vs non-LAAE was 0.672 (95% CI 0.394-1.146). CONCLUSION: In AF patients not taking oral anticoagulation who are at high risk for stroke and for bleeding, minimally invasive, thoracoscopic, epicardial LAAE was associated with a lower rate of thromboembolic events.

Ten-Year Review of Antihypertensive Prescribing Practices After Stroke and the Associated Disparities From the Florida Stroke Registry.

BACKGROUND: Guideline-based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescriber's blood pressure (BP) medication choice adheres to clinical practice guidelines (BP-guideline adherence). METHODS AND RESULTS: The FSR (Florida Stroke Registry) uses statewide data prospectively collected for all acute stroke admissions. Based on established guidelines, we defined optimal BP-guideline adherence using the following hierarchy of rules: (1) use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker as first-line antihypertensive among diabetics; (2) use of thiazide-type diuretics or calcium channel blockers among Black patients; (3) use of beta blockers among patients with compelling cardiac indication; (4) use of thiazide, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or calcium channel blocker class as first line in all others; (5) beta blockers should be avoided as first line unless there is a compelling cardiac indication. A total of 372 254 cases from January 2010 to March 2020 are in the FSR with a diagnosis of acute ischemic stroke, hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage; 265 409 with complete data were included in the final analysis. Mean age was 70±14 years; 50% were women; and index stroke subtypes were 74% acute ischemic stroke, 11% intracerebral hemorrhage, 11% transient ischemic attack, and 4% subarachnoid hemorrhage. BP-guideline adherence to each specific rule ranged from 48% to 74%, which is below quality standards of 80%, and was lower among Black patients (odds ratio, 0.7 [95% CI, 0.7-0.83]; P<0.001) and those with atrial fibrillation (odds ratio, 0.53 [95% CI, 0.50-0.56]; P<0.001) and diabetes (odds ratio, 0.65 [95% CI, 0.61-0.68]; P<0.001). CONCLUSIONS: This large data set demonstrates consistently low rates of BP-guideline adherence over 10 years. There is an opportunity for monitoring hypertensive management after stroke.

Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.

Direct Oral Anticoagulant Failures in Atrial Fibrillation With Stroke: Retrospective Admission Analysis and Novel Classification System.

Introduction: Breakthrough acute ischemic stroke (AIS) in patients with known, nonvalvular Atrial Fibrillation (AF), on Direct Oral Anticoagulants (DOAC), is an ongoing clinical conundrum. Switching anticoagulants was shown to be ineffective in preventing recurrent AIS. Systematic, patient-level chart review of so-called "DOAC failures" may offer insight into this phenomenon. Methods: We conducted an IRB-approved, 6-year, retrospective study of AIS admissions, already prescribed DOAC for known AF. We sought plausible, alternative reasons for the AIS using a novel classification schema, CLAMP: C for Compliance concerns, L for Lacunes (small-vessel disease), A for Arteriopathy (atherosclerosis, web, or vasculitis), M for Malignancy, and P for Patent Foramen Ovale (PFO). These categories were labeled as DOAC "Pseudo-failures." Conversely, absence of CLAMP variables were labeled as DOAC "Crypto-failures" conceivably from AF itself ("atriopathy") or pharmacokinetic/pharmacogenomic dysfunction (ie, altered DOAC absorption, clearance, metabolism, or genetic polymorphisms). Forward logistic regression analysis was performed on prespecified DOAC subgroups. Results: Of 4890 AIS admissions, 606 had AF, and 87 were previously prescribed DOAC (14.4% overall DOAC failure rate, 2.4% annualized over 6 years). Pseudo-failures comprised 77%: Compliance concerns (48.9%), Lacunes (5.7%), Arteriopathy (17.0%), Malignancy (26.1%), and PFO (2.3%). Crypto-failures comprised 23%, had lower CHADSVASc scores (AOR = .65, P = .013), and occurred more with rivaroxaban (41%) than apixaban (16%) or dabigatran (5.6%). Conclusion: In AIS patients with known AF, DOAC Pseudo-failures, with identified alternate etiologies, are 3 times more likely than DOAC Crypto-failures. The CLAMP schema represents a novel approach to diagnostic classification and therapeutic adjustments in patients already prescribed DOAC for AF.

Predictors and Temporal Trends of Withdrawal of Life-Sustaining Therapy After Acute Stroke in the Florida Stroke Registry.

Temporal trends and factors associated with the withdrawal of life-sustaining therapy (WLST) after acute stroke are not well determined. DESIGN: Observational study (2008-2021). SETTING: Florida Stroke Registry (152 hospitals). PATIENTS: Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Importance plots were performed to generate the most predictive factors of WLST. Area under the curve (AUC) for the receiver operating curve were generated for the performance of logistic regression (LR) and random forest (RF) models. Regression analysis was applied to evaluate temporal trends. Among 309,393 AIS patients, 47,485 ICH patients, and 16,694 SAH patients; 9%, 28%, and 19% subsequently had WLST. Patients who had WLST were older (77 vs 70 yr), more women (57% vs 49%), White (76% vs 67%), with greater stroke severity on the National Institutes of Health Stroke Scale greater than or equal to 5 (29% vs 19%), more likely hospitalized in comprehensive stroke centers (52% vs 44%), had Medicare insurance (53% vs 44%), and more likely to have impaired level of consciousness (38% vs 12%). Most predictors associated with the decision to WLST in AIS were age, stroke severity, region, insurance status, center type, race, and level of consciousness (RF AUC of 0.93 and LR AUC of 0.85). Predictors in ICH included age, impaired level of consciousness, region, race, insurance status, center type, and prestroke ambulation status (RF AUC of 0.76 and LR AUC of 0.71). Factors in SAH included age, impaired level of consciousness, region, insurance status, race, and stroke center type (RF AUC of 0.82 and LR AUC of 0.72). Despite a decrease in the rates of early WLST (< 2 d) and mortality, the overall rates of WLST remained stable. CONCLUSIONS: In acute hospitalized stroke patients in Florida, factors other than brain injury alone contribute to the decision to WLST. Potential predictors not measured in this study include education, culture, faith and beliefs, and patient/family and physician preferences. The overall rates of WLST have not changed in the last 2 decades.

Preexisting Depression and Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project. METHODS: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined. RESULTS: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex. CONCLUSIONS: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge.

Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials.

INTRODUCTION: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. METHODS: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). CONCLUSIONS: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

A 10-year review of antihypertensive prescribing practices after stroke and the associated disparities from the Florida Stroke Registry.

Background: Guideline based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescribers' blood pressure medication choice adheres to clinical practice guidelines (Prescribers'-Choice Adherence). Methods: The Florida Stroke registry (FSR) utilizes statewide data prospectively collected for all acute stroke admissions. Based on established guidelines we defined optimal Prescribers'-Choice Adherence using the following hierarchy of rules: 1) use of an angiotensin inhibitor (ACEI) or angiotensin receptor blocker (ARB) as first-line antihypertensive among diabetics; 2) use of thiazide-type diuretics or calcium channel blockers (CCB) among African-American patients; 3) use of beta-adrenergic blockers (BB) among patients with compelling cardiac indication (CCI) 4) use of thiazide, ACEI/ARB or CCB class as first-line in all others; 5) BB should be avoided as first line unless CCI. RESULTS: A total of 372,254 cases from January 2010 to March 2020 are in FSR with a diagnosis of acute ischemic, hemorrhagic stroke, transient ischemic attack or subarachnoid hemorrhage; 265,409 with complete data were included in the final analysis. Mean age 70 +/-14 years, 50% female, index stroke subtype of 74% acute ischemic stroke and 11% intracerebral hemorrhage. Prescribers'-Choice Adherence to each specific rule ranged from 48-74% which is below quality standards of 85%. There were race-ethnic disparities with only 49% Prescribers choice Adherence for African Americans patients. Conclusion: This large dataset demonstrates consistently low rates of Prescribers'-Choice Adherence over 10 years. There is an opportunity for quality improvement in hypertensive management after stroke.

Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows.

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. RESULTS: Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. CONCLUSIONS: In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.

Nationally Certified Stroke Centers Outperform Self-Attested Stroke Centers in the Florida Stroke Registry.

BACKGROUND: The Florida Stroke Act, signed into law in 2004, set criteria for Comprehensive Stroke Centers (CSC). For a set time period, Florida hospitals were permitted to either receive national certification (NC) or could self-attest (SA) as fulfilling CSC criteria. The aim of this project was to evaluate the quality of ischemic stroke care in NC versus SA stroke centers in Florida, using well-known, guideline-driven ischemic stroke outcome metrics. METHODS: A total of 37 CSCs (74% of Florida CSCs) in the Florida Stroke Registry from January 2013 through December 2018 were analyzed, including 19 SA CSCs and 18 NC (13 CSCs and 5 Thrombectomy-Capable Stroke Center). Hospital- and patient-level characteristics and stroke metrics were evaluated, adjusting for demographics, medical comorbidities, and stroke severity. RESULTS: A total of 78 424 acute ischemic stroke cases, 36 089 from SA CSCs and 42 335 from NC CSC/Thrombectomy-Capable Stroke Centers were analyzed. NC centers had older patients (73 [61-83] versus 71 [60-81]; P<0.001) with more severe strokes (median National Institutes of Health Stroke Scale score of 5 versus 4; P<0.001). NC had higher intravenous tissue-type plasminogen activator utilization (15% versus 13%; P<0.001), endovascular treatment (10% versus 7%; P<0.001) and faster median door-to-computed tomography (23 minutes [11-73] versus 31 [12-78]; P<0.001), door-to-needle (37 minutes [26-50] versus 45 [34-58]; P<0.001) and door-to-puncture times (77 minutes [50-113] versus 93 [62-140]; P<0.001). In adjusted analysis, patients arriving to NC hospitals by 3 hours were more likely to get intravenous tissue-type plasminogen activator in the 3- to 4.5-hour window (adjusted odds ratio, 1.87 [95% CI, 1.30-2.68]; P=0.001) and more likely to be treated with intravenous tissue-type plasminogen activator within 45 minutes (adjusted odds ratio, 1.61 [95% CI, 1.04-2.50]; P=0.04) compared with SA CSCs. CONCLUSIONS: Among Florida-Stroke Registry CSCs, acute ischemic stroke performance and treatment measures at NC centers are superior to SA CSCs. These findings have implications for stroke systems of care in Florida and support legislation updates requiring NC and removal of SA claims.

Web Browsing: High-Speed Diagnosis and Treatment of Carotid Artery Web.

Background: Although carotid artery web (CaW) was initially described in 1973 as a potential etiology of ischemic stroke, it still remains underrecognized. Because CaW is a membrane affixed perpendicularly from the carotid wall that projects out into the lumen above the bifurcation, it typically is not stenotic, and hence, utilizing only 1 vessel imaging modality during conventional stroke workup may instead lead to a diagnosis of ESUS: embolic stroke of undetermined source. The term ESUS was created in 2014 by researchers to define a subset of cryptogenic, nonlacunar (embolic-appearing) strokes without clear cardiac or vascular cause. Purpose: In this review, we describe how, after multiple evaluations of vessels, CaW was diagnosed in relatively young patients (age 39-47 years old, without significant vascular risk factors) in whom otherwise were considered embolic stroke of undetermined source. This observation dovetails with the accompanying Neurohospitalist article entitled, "Delayed Thrombus Formation on Carotid Web and Its Medical and Endovascular Management for Secondary Stroke Prevention." Research Design: Not applicable. Case review. Results/Conclusion: This report demonstrates the futility of antiplatelet therapy for a young patient with CaW-related stroke. Based on these collective experiences and review of the literature, we postulate that: (1) multiple vascular imaging modalities during stroke workup may result in a CaW diagnosis instead of ESUS; (2) young stroke patients without traditional vascular risk factors are candidates for this "web browsing" of extended imaging of vessels; and (3) carotid artery stenting (CAS) or carotid endarterectomy (CEA) may be preferred as first-line over medical therapy alone (ie, antiplatelet or anticoagulation) because CEA/CAS addresses the stroke etiology, CaW, definitively.

No Time to Lose: Cases of Anticoagulant Reversal Before Thrombolysis in Acute Ischemic Stroke Patients.

Direct oral anticoagulant (DOAC) reversal before intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients is well-documented in Europe, specifically for dabigatran: the selective humanized monoclonal antibody fragment idarucizumab, given to neutralize dabigatran prior to IVT, was associated with improved outcomes post-IVT. However, in the United States, this approach is rarely reported and not endorsed by guidelines. Therefore, further reporting on this is needed and neuroradiographic correlation may help validate this concept. At our hospital in Tampa, Florida, two octogenarians with atrial fibrillation, adherent with the DOAC dabigatran, presented with AIS shortly after symptom onset. Both received idarucizumab, then IVT. Clinical outcomes, treatment times, and perfusion-based neuroradiographic parameters were assessed. Patient A had a 41 ml penumbra on computed tomography perfusion (CTP) scan that decreased to 15 ml in final infarct volume on follow-up imaging, resulting in a 26 ml penumbral salvage (63.4%), and National Institutes of Health Stroke Scale (NIHSS) improved from 11 to 9 . Patient B had a 23 ml penumbra on CTP that decreased to 0.5 ml on follow-up imaging, resulting in a 22.5 ml penumbral salvage (97.8%), and NIHSS improved from 9 to 4. Neither developed bleeding complications. Both had delayed door-to-needle times but nevertheless demonstrated clinical neurological improvements. In our limited experience, IVT after immediate DOAC reversal in AIS patients on dabigatran was associated with clinical improvement in NIHSS by 2 to 5 points (with no neuroworsening), and penumbral salvage of ischemic brain tissue on neuroimaging ranging from 63.4% to 97.8%. Further reporting on this may lead to greater IVT use and better outcomes in "DOAC failures", especially for patients without other acute treatment options such as mechanical thrombectomy. Research into other anticoagulant reversal agents pre-IVT in AIS is also warranted.

Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial.

BACKGROUND AND PURPOSE: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. METHODS: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS. RESULTS: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P=0.78), death (4.9% versus 8.5%, P=0.68), fatal strokes (2.4% versus 8.5%, P=0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P=0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. CONCLUSIONS: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.

Untreated Stroke as Collateral Damage of COVID-19: "Time Is Brain" Versus "Stay at Home".

For decades, neurologists have been advocating that anyone with acute focal deficits report immediately to the closest hospital's emergency room. Major advancements in the hyperacute diagnosis and treatment of stroke have justified our call-to-action slogan of "Time is Brain"-faster therapy leads to superior outcomes. However, this mantra has been recently usurped by the catchphrase "Stay at Home" during the coronavirus disease 2019 (COVID-19) pandemic. Fewer patients are presenting to hospitals with acute stroke; our census is down. Presumably the etiology of this phenomenon is either strict "social distancing" that some people may misperceive to exclude even emergent situations, or fears of contracting the virus while hospitalized. In this Short Report, we describe the year-over-year drop in stroke volume (ischemic and hemorrhagic both) coinciding with a paradoxical rise in acute reperfusion therapies at our university hospital. These data imply that stroke patients with mild/moderate symptoms are most likely staying home, and not receiving urgent therapies, and correspondingly, only the most severely disabled stroke patients are ultimately seeking and receiving help. We must remind our patients and the general public that our services are essential and available, as stroke still remains a medical emergency, and carries a likely higher overall mortality risk than COVID-19. As neurologists, we also must be vigilant for the atypical presentations and varied etiologies of stroke associated with COVID-19 as well.