American Heart Association

treatment

Endovascular Thrombectomy With or Without Intravenous Alteplase: ESO-WSO Large Clinical Trials Webinar

Parneet Grewal, MD
@parneetgrewal6

ESO-WSO 2020 Large Clinical Trials Webinar
Presenter: Dr. Jianmin Liu (China)
Article: Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, et al, for the DIRECT-MT Investigators. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. NEJM. 2020.

The goal of current therapeutic strategies for acute ischemic stroke with large vessel occlusion (LVO) is recanalization of the occlusion before irreversible damage has occurred. In this large multicenter, prospective, randomized, open-label trial with blinded outcome assessment, Dr. Jianmin Liu and his team aimed to answer the question of whether mechanical thrombectomy (MT) alone (thrombectomy alone group) would be non-inferior to combined treatment of IV-tPA and MT (combined group) in patients with LVO.  

This trial included patients ³ 18 years of age who presented to 41 pre-selected academic medical centers in China within 4.5 hours of symptom onset, had National Institutes of Health Stroke Scale (NIHSS) ³ 2 with imaging showing an LVO (intracranial segment of ICA, M1 or proximal M2 only). Any patients who did not meet American Heart Association/American Stroke Association guidelines for alteplase or MT were not included in the trial. The standard dose of tPA at 0.9 mg/kg was used, and the first-line strategy for MT was stent-retriever. Statistically, the trial was designed to provide 80% power (at a two-sided alpha level of 0.05) to determine a non-inferiority margin of 0.8. 656 patients were randomized in 1:1 fashion by a web-based system with 327 patients in the thrombectomy alone group and 329 patients in the combined group. The patient enrollment period was 17 months (February 23, 2018, to July 2, 2019). The baseline characteristics of patients were similar in both the groups with a median age of 69 years, median NIHSS score of 17, and median ASPECTS value of 9. The median duration from stroke onset to randomization was 167 minutes in the thrombectomy alone group and 177 minutes in combined group with time from randomization to groin puncture being 31 minutes and 36 minutes, respectively.

ESO-WSO Large Clinical Trials Webinar: BASICS

Rachel Forman, MD
@bustinclots247

I was happy to see that although the ESO-WSO 2020 annual meeting was postponed, we still had the opportunity to virtually hear the results of some recent large clinical trials. One of the five trials presented was the Basilar Artery International Collaboration Study (BASICS) presented by Dr. Wouter Schonewille from The Netherlands. Posterior circulation occlusions have been largely excluded from the main endovascular randomized control trials, so these results were highly anticipated. 

Many of us are familiar with the devastating effects of a basilar artery occlusion (BAO), and from a personal experience, some of these cases have been very challenging without having the guidance of large trials as we do with anterior circulation occlusions. The clinical presentations, stroke severity, and collateral patterns are inherently different. This trial was an international, multicenter, controlled trial with randomized treatment-group assignments investigating the efficacy and safety of endovascular therapy (EVT) plus best medical management (BMM) versus BMM alone <6 hours of estimated time of BAO. Patients were randomly assigned (1:1 ratio) to EVT+BMM or BMM alone and stratified according to: randomizing center, use of IVT, and NIHSS (<20 vs >20). The enrollment period was from 2011 through 2019. Patients were excluded with intracranial hemorrhage, extensive brainstem ischemia, or cerebellar mass effect/acute hydrocephalus. The calculated sample size was 300 patients assuming favorable outcome in 46% with EVT+BMM and 30% with BMM. Primary outcome was mRS <3 at 90 days. Secondary outcome measures included clinical outcomes (mRS 0-2 at 90 days and mRS distribution) and imaging outcomes (posterior circulation ASPECTS score at 24 hours and basilar artery patency at 24 hours). 

Article Commentary: “Mechanical Thrombectomy in the Era of the COVID-19 Pandemic: Emergency Preparedness for Neuroscience Teams”

Gurmeen Kaur, MBBS
@kaurgurmeen

Nguyen TN, Abdalkader M, Jovin TG, Nogueira RG, Jadhav AP, Haussen DC, et al. Mechanical Thrombectomy in the Era of the COVID-19 Pandemic: Emergency Preparedness for Neuroscience Teams: A Guidance Statement From the Society of Vascular and Interventional Neurology. Stroke. 2020.

With the COVID-19 pandemic taking more than 50,000 lives in the United States, emergency medical services are being forced to change their triage policies in order to ensure safety of both the patients and the health care personnel involved.

Stroke and STEMI triage systems are among the first to be affected, especially because there is some evidence for the increased incidence of acute ischemic strokes in COVID-19 patients, secondary to the hypercoagulability.

The Society of Vascular and Interventional Neurology has issued a guidance statement highlighting practices that all institutes should be incorporating into their routine stroke workflow — pre-, intra- and post-mechanical thrombectomy. These guidelines serve as pointers that can be used to modify our existing protocols. Because we are going to continue to see the effect of COVID-19 through the summer, especially in highly impacted states like New York, Massachusetts and Illinois, and there is also a potential second wave predicted for fall and winter 2020, it is prudent that all centers adopt these best practice guidelines in their daily stroke triage and workflow.

Article Commentary: “Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection”

Muhammad Rizwan Husain, MD
@RIZWANHUSAINMD

Markus HS, Levi C, King A, Madigan J, Norris J, for the Cervical Artery Dissection in Stroke Study (CADISS) Investigators. Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection: The Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results. JAMA Neurol. 2019;76:657-664.

Cervical artery dissection (CAD) has an annual incidence of about 2.9% per 100,000, though that seems to be under-reported, as many patients usually do not present for evaluation or undergo routine vessel imaging for local symptoms like pain or headache. At the same time, even though CAD accounts for about 1-2% of total ischemic strokes, it can be the cause of up to 25% of strokes in the young population.

The Cervical Artery Dissection in Stroke Study (CADISS) is the only prospective randomized clinical trial to date that evaluated if there was a reduction in subsequent stroke in patients treated with either antiplatelet or anticoagulation. It also looked at the presence of arterial recanalization between the two groups.

Mechanical Thrombectomy in Vertebrobasilar Occlusion: Still Looking for Evidence

Elena Zapata-Arriaza, MD
@ElenaZaps

Liu X, Dai Q, Ye R, Zi W, Liu Y, Wang H, et al. Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial. Lancet Neurol. 2020;19:115-122.

Efficacy and safety of endovascular treatment (EVT) in anterior circulation strokes is clearly validated; however, such evidence is still lacking in vertebrobasilar occlusions. Liu et al. aimed to demonstrate safety and efficacy of EVT in posterior circulation strokes. To achieve this goal, the authors performed a multicenter, randomized, open-label trial in patients within 8 h of vertebrobasilar occlusion (basilar or V4 segment of vertebral artery). Patients were allocated to receive either EVT plus standard medical therapy or standard medical therapy alone. Given endovascular procedure, stent-retriever was the most employed technique, but thromboaspiration, intra-arterial thrombolysis, balloon angioplasty or stenting were also permitted. Primary outcome was mRS 0-3 at 90 days, assessed on an intention-to-treat basis. Primary safety outcome was mortality at 90 days. Secondary safety endpoints included symptomatic intracranial hemorrhage, device-related complications and other severe events rates. Each participating center had to have completed at least 5 mechanical thrombectomy procedures with stent retriever devices in the preceding year. The primary data analysis was done on the intention-to-treat population. In addition, secondary prespecified analyses were performed in the per-protocol population and in the as-treated population.

Author Interview: Dr. Houman Khosravani, MD, PhD, on “Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease 2019 (COVID-19) Pandemic”

Houman Khosravani
Houman Khosravani

A conversation with Houman Khosravani, MD, PhD, Assistant Professor, Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada. Twitter: @neuroccm

Interviewed by Victor J. Del Brutto, MD, Assistant Professor, Stroke Division, Department of Neurology, University of Miami Miller School of Medicine, Florida. Twitter: @vdelbrutto

They will be discussing the paper “Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease 2019 (COVID-19) Pandemic,” published in Stroke.

Dr. Del Brutto: First of all, I would like to thank you and your team for putting together these thoughtful recommendations on how to evaluate patients with suspected stroke during the Coronavirus Disease 2019 (COVID-19) pandemic. As a stroke neurologist, I share the global feeling of uncertainty that this pandemic has caused and look forward to modifying my institution practices in order to maximize patients’ outcomes, their safety, and the safety of the professionals involved in their care. In your article, you mention that stroke patients are at an increased risk of suboptimal outcomes during the COVID-19 pandemic. Could you please comment on the factors that may influence patient outcomes?

Dr. Khosravani: During the COVID-19 pandemic, patients are affected at several junctions in stroke care, including during the hyperacute phase. For example, paramedics responding to a stroke call, in some jurisdictions, will begin the screening process prior to arrival and then again on scene. When screening is positive, pre-notification to the hospital should occur, and this triggers a protected code stroke (PCS). Patients being brought directly to the ED will require additional screening. The necessary use of PPE, with a Safety Lead observing, will add some delays to the front-end processes, but these are essential to keeping providers safe. It is very plausible that, for example, door-to-needle/door-to-groin puncture times will be impacted. Similarly, at the point-of-care, a COVID-19–suspected patient going to imaging will result in having special precautions used in the scanner or neuroangiography suite, which will add additional time (for cleaning as well); this impacts scenarios with back-to-back code strokes as well.

Thrombus Migration in Large Vessel Occlusion: Is it Good or Bad?

Ravinder-Jeet Singh, MBBS, DM

Alves HC, Treurniet KM, Jansen IGH, Yoo AJ, Dutra BG, Zhang G, et al. Thrombus Migration Paradox in Patients with Acute Ischemic Stroke. Stroke. 2019; 50:3156-3163.

Thrombus is a dynamic structure with constantly changing size, morphology and location over time, to variable extent in each patient, before recanalization occurs. Recently, there is interest in understanding dynamic clot features, especially regarding thrombus movement — defined as change in the occlusion site — between initial (typically CT angiogram) and follow-up vascular imaging (usually catheter angiogram for mechanical thrombectomy). Whether thrombus migration before recanalization is of any clinical or functional significance remains under investigation. The thrombus migration was studied in the past.1 It underlies a clinical phenomenon called “spectacular shrinking deficit,” in which a patient with major hemispheric syndrome shows rapid (over minutes to hours) and dramatic improvement or disappearance of most clinical deficits.1 Use of regular “vascular imaging” now allows investigating the concept in reverse order, i.e., the incidence thrombus migration and correlate it with clinical change or functional outcome. Different factors determine the dynamic behavior of the clot, including source of thrombus (etiology of stroke), composition of the thrombus, initial thrombus location within arterial tree (for example, proximal vs distal occlusion), angioarchitecture around the thrombus and use of intravenous thrombolysis (IVT).1-4

Stroke Codes for Nonagenarians

Richard Jackson, MD

Drouard-de Rousiers E, Lucas L, Richard S, Consoli A, Mazighi M, Labreuche J, et al. Impact of Reperfusion for Nonagenarians Treated by Mechanical Thrombectomy: Insights From the ETIS Registry. Stroke. 2019;50:3164–3169.

Dr. Drouard-de Rousiers et al. performed a retrospective analysis of all patients over 90 years old who received endovascular therapy in the Endovascular Treatment in Ischemic (ETIS) registry from 2013-2018. 

The study is based on observational data retrospectively gathered from multiple sites, all devices were third generation, clinical and radiographic data were evaluated on admission, and CT or MRI was performed between 12 and 72 hours to track hemorrhagic transformation. The patients with successful reperfusion had OR 3.26 of having lower 90-day mRS mainly driven by decreased mortality. The caveat to this benefit is that procedural complications were 16.5% including vessel perforations and dissections.

Article Commentary: “One-Year Home-Time and Mortality After Thrombolysis Compared With Nontreated Patients in a Propensity-Matched Analysis”

Jennifer Harris, MD
@JenHarrisMD

Yu AYX, Fang J, Kapral MK. One-Year Home-Time and Mortality After Thrombolysis Compared With Nontreated Patients in a Propensity-Matched Analysis. Stroke. 2019;50:3488–3493.

Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (r-tPA) is an effective treatment in acute ischemic stroke. Several studies have examined functional outcome and mortality at 3 months after intravenous r-tPA treatment. However, data on long-term outcome are limited. Two randomized controlled stroke trials, the National Institute of Neurological Disorders and Stroke trial (NINDS) and the third International Stroke Trial (IST-3), have examined long-term mortality after intravenous r-tPA and revealed no differences in mortality rates among treated and nontreated patients at 12- and 18-months follow-up, respectively.

To explore long-term clinical outcome after intravenous r-tPA, Yu et al. conducted a nationwide register-based follow up study using a propensity score matching method. Using the Ontario Stroke Registry, they identified 29,036 patients with ischemic stroke and used propensity score methods to match the 4,449 patients treated with intravenous r-tPA to nontreated patients. The primary outcome was 1-year home-time, which was defined as the number of days spent outside of any healthcare institutions, and showed that compared with nontreated patients, those treated with intravenous r-tPA experienced a mean of 9.5 additional days at home in the first year. Now, while looking at these results from an individual patient perspective, this might seem like a rather small improvement; however, looking at the larger picture, it can mean significant cost savings for the healthcare system at large. With roughly 700,000 ischemic strokes occurring annually in the United States, and associated stroke care costs estimated at $34 billion each year, even a small increase in the rate of thrombolysis could potentially lead to reduced hospital stays and large costs savings.

Article Commentary: “Advances and Innovations in Aphasia Treatment Trials”

Burton J. Tabaac, MD
@burtontabaac

Berube S, Hillis AE. Advances and Innovations in Aphasia Treatment Trials. Stroke. 2019;50:2977–2984.

Aphasia is a disorder that results from damage to portions of the brain that are responsible for language. For most people, these areas reside in the left hemisphere of the brain. Aphasia usually occurs suddenly, often following a stroke or head injury, but it may also develop slowly, as the result of a brain tumor or a progressive neurological disease. The disorder impairs the expression and understanding of language, as well as reading and writing. Aphasia may co-occur with speech disorders, such as dysarthria or apraxia of speech, which also result from brain damage.1 This Stroke article summarizes advances in clinical trials of aphasia, secondary to stroke, and the treatment studied from clinical trials over the past 5 years. The authors discuss noninvasive brain stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation, as well as pharmacological and medical interventions.

Drs. Berube and Hillis noted, “methodological weaknesses in many of the aphasia treatment studies compromise strong conclusions about efficacy.” Interestingly, the authors added, “The distribution of aphasia subtypes might influence efficacy … it is possible that individuals with Broca’s aphasia respond more to certain types of treatment, while those with Wernicke’s aphasia respond more to other types. However, none of the studies have been adequately powered to identify differential efficacy across subtypes.” Drs. Berube and Hillis concluded in their review that the most effective or efficient interventions currently available combine novel Speech-Language Therapy (SLT) with noninvasive brain stimulation (NIBS) or medications.