Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Mechanical Thrombectomy Global Access For Stroke (MT-GLASS): A Mission Thrombectomy (MT-2020 Plus) Study.

BACKGROUND: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. METHODS: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. RESULTS: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70-11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower-middle versus high: odds ratio, 0.08 [95% CI, 0.04-0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07-5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84-4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70-9.42]) were significantly associated with increased odds of MTA. CONCLUSIONS: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country's per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Racial Disparity in Mechanical Thrombectomy Utilization: Multicenter Registry Results From 2016 to 2020.

Background Previous studies on racial disparity in mechanical thrombectomy (MT) treatment of acute large vessel occlusion stroke lack individual patient data that influence treatment decision-making. We assessed patient-level data in a large US health care system from 2016 to 2020 for racial disparities in MT utilization and eligibility. Methods and Results A retrospective study was performed of 34 596 patients admitted to 43 hospitals from January 2016 to September 2020. Data included patient age, sex, race, residential zip code median income and population density, presenting hospital stroke certification, baseline ambulation, and National Institutes of Health stroke scale. The cohort included 26 640 White, non-Hispanic (77.0%), and 7956 African American/Black (23.0%) patients. In multivariable logistic regression, Black patients were less likely to undergo MT (adjusted odds ratio [OR], 0.65; 95% CI, 0.54-0.76), arrive within 5 hours of "last known well" (adjusted OR, 0.73; 95% CI, 0.69-0.78), and have documented anterior circulation large vessel occlusion (adjusted OR, 0.78; 95% CI, 0.64-0.96). Race was not associated with MT rate among patients arriving within 5 hours of last known well with documented acute large vessel occlusion. Conclusions Black patients with stroke underwent MT less frequently than White patients, likely in part because of longer times from last known well to hospital arrival and a lower rate of documented acute large vessel occlusion. Further studies are needed to assess whether extending the MT time window and more aggressive large vessel occlusion screening protocols mitigate this disparity.

Mechanical Thrombectomy Access for All? Challenges in Increasing Endovascular Treatment for Acute Ischemic Stroke in the United States.

Mechanical thrombectomy (MT) is the most effective treatment for selected patients with an acute ischemic stroke due to emergent large vessel occlusions (LVOs). There is an urgent need to identify and address challenges in access to MT to maximize the numbers of patients who can benefit from this treatment. Barriers in access to MT include delays in evaluation and accurate diagnosis of LVO leading to inappropriate triage, logistical delays related to availability of facilities and trained interventionalists, and financial hurdles that affect treatment reimbursement. Collection of regional data related to these barriers is critical to better understand current access gaps and a measurable access score to thrombectomy could be useful to plan local public health intervention.

Patient Characteristics and Outcomes Associated with Decline in Stroke Volumes During the Early COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Delayed evaluation of stroke may contribute to COVID-19 pandemic-related morbidity and mortality. This study evaluated patient characteristics, process measures and outcomes associated with the decline in stroke presentation during the early pandemic. METHODS: Volumes of stroke presentations, intravenous thrombolytic administrations, and mechanical thrombectomies from 52 hospitals from January 1-June 30, 2020 were analyzed with piecewise linear regression and linear spline models. Univariate analysis compared pandemic (case) and pre-pandemic (control) groups defined in relation to the nadir of daily strokes during the study period. Significantly different patient characteristics were further evaluated with logistic regression, and significantly different process measures and outcomes were re-analyzed after propensity score matching. RESULTS: Analysis of 7,389 patients found daily stroke volumes decreased 0.91/day from March 12-26 (p < 0.0001), reaching a nadir 35.0% less than expected, and increased 0.15 strokes/day from March 27-June 23, 2020 (p < 0.0001). Intravenous thrombolytic administrations decreased 3.3/week from February 19-March 31 (p = 0.0023), reaching a nadir 33.4% less than expected, and increased 1.4 administrations/week from April 1-June 23 (p < 0.0001). Mechanical thrombectomy volumes decreased by 1.5/week from February 19-March 31, 2020 (p = 0.0039), reaching a nadir 11.3% less than expected. The pandemic group was more likely to ambulate independently at baseline (p = 0.02, OR = 1.60, 95% CI = 1.08-2.42), and less likely to present with mild stroke symptoms (NIH Stroke Scale ≤ 5; p = 0.04, OR = 1.01, 95% CI = 1.00-1.02). Process measures and outcomes of each group did not differ, including door-to-needle time, door-to-puncture time, and successful mechanical thrombectomy rate. CONCLUSION: Stroke presentations and acute interventions decreased during the early COVID-19 pandemic, at least in part due to patients with lower baseline functional status and milder symptoms not seeking medical care. Public health messaging and initiatives should target these populations.

Consecutive Endovascular Treatment of 20 Ruptured Very Small (<3 mm) Anterior Communicating Artery Aneurysms.

BACKGROUND: Small aneurysms located at the anterior communicating artery carry significant procedural challenges due to a complex anatomy. Recent advances in endovascular technologies have expanded the use of coil embolization for small aneurysm treatment. However, limited reports describe their safety and efficacy profiles in very small anterior communicating artery aneurysms. OBJECTIVE: We sought to review and report the immediate and long-term clinical as well as radiographic outcomes of consecutive patients with ruptured very small anterior communicating artery aneurysms treated with current endovascular coil embolization techniques. METHODS: A prospectively maintained single-institution neuroendovascular database was accessed to identify consecutive cases of very small (<3 mm) ruptured anterior communicating artery aneurysms treated endovascularly between 2006 and 2013. RESULTS: A total of 20 patients with ruptured very small (<3 mm) anterior communicating artery aneurysms were consecutively treated with coil embolization. The average maximum diameter was 2.66 ± 0.41 mm. Complete aneurysm occlusion was achieved for 17 (85%) aneurysms and near-complete aneurysm occlusion for 3 (15%) aneurysms. Intraoperative perforation was seen in 2 (10%) patients without any clinical worsening or need for an external ventricular drain. A thromboembolic event occurred in 1 (5 %) patient without clinical worsening or radiologic infarct. Median clinical follow-up was 12 (±14.1) months and median imaging follow-up was 12 (±18.4) months. CONCLUSION: This report describes the largest series of consecutive endovascular treatments of ruptured very small anterior communicating artery aneurysms. These findings suggest that coil embolization of very small aneurysms in this location can be performed with acceptable rates of complications and recanalization.

Endovascular reconstruction for progressively worsening carotid artery dissection.

BACKGROUND: Carotid artery dissection is an important cause of stroke in young patients. Selection criteria for endovascular repair have not been well defined and limited data exist on long-term outcomes of stent reconstruction. OBJECTIVE: To report the immediate and long-term clinical and radiographic outcomes of patients treated with stent placement for progressively worsening symptomatic carotid arterial dissection despite antithrombotic therapy. METHODS: A single institution neuro-endovascular database was accessed to identify consecutive cases in which carotid artery dissection was treated with endovascular repair between 2006 and 2012. Clinical, demographic, radiographic, and procedural data were obtained through chart review. RESULTS: A total of 22 patients were identified and included 27 carotid artery dissection repairs with stent implantation. The mean age was 43 years (±8.7) with 13 patients being women. Traumatic dissections were seen in 9 (40.9%) patients and spontaneous dissections in 13 (59.1%) patients. All patients were symptomatic and were started on antithrombotic therapy on diagnosis. Most common indications for treatment included recurrent ischemia despite antithrombotic therapy in 15 (55.5%) arteries and enlarging dissecting aneurysm in 4 (14.8%) arteries. Mean degree of stenosis was 79.1%. Mean number of stents used was 1.88 (range 1-4). There was 1 (4.5%) asymptomatic peri-procedural thromboembolic event. Median clinical follow-up was 14 months (range 3-40) and median imaging follow-up was 14 months (range 3-38). There was 1 (4.5%) case of recurrent transient ischemic attack. There was no death, significant restenosis or stroke in the territory of the treated vessel during the duration of the follow-up. CONCLUSIONS: Endovascular stent reconstruction for the treatment of selected patients with progressively worsening carotid dissection despite medical management is feasible with acceptable immediate and long-term clinical and radiographic outcomes. To be able to draw more robust conclusions, further evaluation with larger number of patients and longer follow-up is needed.

Identifying delays to mechanical thrombectomy for acute stroke: onset to door and door to clot times.

Outcomes from endovascular therapy for acute stroke are time dependent. Delays in the administration of this therapy have not been extensively studied and no performance benchmarks have been established. There are limited data on the complex factors that can affect these delays. In this review, we discuss the existing literature on the delays involved in endovascular therapy and have presented them as prehospital and inhospital factors. Some of these factors are common to intravenous thrombolysis; in addition, there are some that are unique to endovascular therapy. These include the awareness of the first responders, emergency medical services, interhospital transfer and triage systems, activation of the endovascular team, complex imaging decisions, and intraprocedural delays. A thorough understanding of these delays can help identify areas of improvement which may affect clinical outcomes.