American Heart Association


Dual Antiplatelet Therapy: Shotgun or Aiming at Precision Targets?

Thomas Raphael Meinel, MD

Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y, Johnston SC, on behalf of the THALES Steering Committee and Investigators. Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin. Stroke. 2020.

Short-term dual antiplatelet therapy (DAPT) has emerged as a powerful treatment option in patients with non-severe ischemic stroke or high-risk TIA.1 However, the efficacy of antithrombotic therapy might vary according to etiology of the ischemic event.2 Amarenco et al. aimed to investigate whether the efficacy and safety of DAPT with Aspirin plus Ticagrelor as compared to Aspirin differed in the subgroup of patients with minor stroke or TIA due to atherosclerotic vascular disease.

For this purpose, the authors conducted a substudy of the THALES trial including patients aged 40 years or older with non-severe non-cardioembolic ischemic stroke (NIHSS ≤5) or high-risk TIA (ABCD2-Score ≥6 or vascular stenosis ≥50% in the suspected vascular territory). Main exclusion criteria were atrial fibrillation, suspicion of cardioembolic cause, high bleeding risk and — importantly — planned carotid revascularization that required halting study medication within 3 days of randomization. or the main prespecified analysis, atherosclerotic ipsilateral stenosis was defined as presence of narrowing of the lumen of ≥30% ipsilateral to the ischemic event as assessed by CT- or MR-angiography or neurovascular ultrasound. The primary efficacy endpoint was time from randomization to the first subsequent event of stroke or death. The primary safety endpoint was occurrence of a severe bleeding event according to the GUSTO definition. 11,016 patients underwent randomization (roughly 50% representing a European and 40% Asian population).

World Stroke Day: The Long Journey of Revascularization Treatments for Ischemic Stroke: From Strict Patient Selection to Extending Time Windows

Raffaele Ornello, MD

Until the early 1990s, stroke was regarded as a disabling event with no cure. The NINDS trial of intravenous thrombolysis, published in 1995, changed the minds of stroke physicians and marked the rise of revascularization treatments for acute ischemic stroke. The initial criteria for patient selection were very strict. After that, more and more refined protocols were established, allowing the progressive extension of the therapeutic window and the loosening of selection criteria.

The last decade saw the rise of endovascular treatments. After the first unsuccessful trials, adequate protocols for the selection of patients with salvageable brain ischemic tissue led to success in recanalization treatments. Better use of brain neuroimaging led to refinements in patient selection, allowing the extension of time windows for treatments in eligible patients. Over the years, revascularization treatments for ischemic stroke spread over most hospitals in the world, allowing widespread access to treatments.

World Stroke Day: Interview with Dr. Anna Bersano on the Impact of the COVID-19 Pandemic on Stroke Care in Italy

Dr. Anna Bersano
Dr. Anna Bersano

An interview with Dr. Anna Bersano, MD, PhD, at the Cerebrovascular Unit of Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, about the impact of the COVID-19 pandemic on stroke care in Italy.

Interviewed by Francesca Tinelli, MCs, rare cerebrovascular disease fellow at Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Dr. Tinelli: First of all, I present you Dr. Anna Bersano, the neurologist I work with, and I would like to thank Anna for agreeing to do this interview. 

Anna is a stroke neurologist with long-term expertise in cerebrovascular diseases, particularly in genetics of monogenic and complex stroke diseases, combining research with an active practice as a vascular care neurologist. She coordinated several studies on genetics of stroke, such as the Lombardia GENS study on stroke monogenic disease and the SVE-LA study on genetics of small vessel disease and lacunar stroke. Recently, she implemented an Italian network for the study of Moyamoya disease named GE-NO-MA (Genetics of Moyamoya Disease) and an Italian network for the study of Cerebral Amyloid Angiopathy (SENECA project). 

Dr. Bersano: Thank you for discussing this relevant and critical topic in the current situation.

Dr. Tinelli: What is the correlation between SARS-CoV2 and cerebrovascular diseases?

Dr. Bersano: It is well known that SARS-CoV2 invades human respiratory epithelial cells through its S-protein and ACE2 receptor on human cell surface. Then, the virus can spread from the respiratory tract to the central nervous system, causing possible neurological complications. A recent study on 214 Chinese COVID-19 patients reported acute cerebrovascular events in 5.7% of COVID-19 patients. However, the exact relationship between SARS-CoV2 and stroke is unclear. Patients affected by COVID-19 have been observed to have a higher risk of cerebrovascular events, probably due to the activation of coagulation and inflammatory pathways, which lead to cardiovascular and thrombotic complications, or to cardioembolic causes.

Chaos About Treatment of Chaotic Heartbeat in Elderly Patients

Nurose Karim, MD

Okumura K, Akao M, Yoshida T, Kawata M, Okazaki O, Akashi S, Eshima K, Tanizawa K, Fukuzawa M, Hayashi T, et al. Low-Dose Edoxaban in Very Elderly Patients with Atrial Fibrillation. N Engl J Med. 2020.

Treatment of atrial fibrillation (AF) in the elderly population has always been challenging. Fragile age, multiple comorbidities, and fall risk put them as a red flag whenever a decision to anticoagulate them is made. Edoxaban is a direct oral factor Xa inhibitor. Studies have been done comparing low dose Edoxaban with warfarin and have found Edoxaban once-daily regimens noninferior to warfarin with respect to the prevention of stroke or systemic embolism and have been associated with significantly lower rates of bleeding and death from cardiovascular causes.1

The Edoxaban Low-Dose for EldeR CARE AF patients (ELDERCARE-AF) study is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study comparing the safety and efficacy of once-daily edoxaban 15 mg versus placebo in Japanese patients with NVAF ≥80 years of age who are considered ineligible for standard oral anticoagulant therapy.2

A Collateral Dialogue: Addressing Neuroanatomy of Posterior Circulation in Basilar Artery Occlusion

Saurav Das, MD

Kwak HS, Park JS. Mechanical Thrombectomy in Basilar Artery Occlusion: Clinical Outcomes Related to Posterior Circulation Collateral Score. Stroke. 2020;51:2045–2050.

The successful endovascular treatment (EVT) trials for large vessel occlusion (LVO) strokes have excluded patients with basilar artery occlusion (BAO). Recently, the results of the Basilar Artery International Collaboration Study (BASICS) were presented at the European Stroke Organization (ESO-WSO) virtual platform. The results, even though underpowered to show significant benefits of EVT <6 hours of BAO, were effective in patients with moderate to severe deficits (NIHSS > 10). The trial results have shifted the spotlight to the distinction in the neuro-anatomy of posterior-circulation vessels and collateral circulation in this part of the brain, etio-pathological mechanisms involved in large vessel disease in the posterior circulation, as well as appropriate patient selection based on symptom severity and time window from symptom onset. In this blog, I will discuss a retrospective study from South Korea relevant to this topic that was published in the July issue of Stroke.

In this study, the authors present data from 81 patients with acute BAO treated with EVT using manual aspiration or stent retriever at their institute in South Korea over a period of eight years from 2012 to 2019. Posterior circulation collaterals were graded using the Basilar Artery on CT Angiogram (BATMAN) score and posterior circulation collateral score (PC-CS). Both these scoring systems have a maximum possible score of 10 points. 64% of these patients achieved TICI 2b or 3 recanalization within a median time of 5.5 hours from symptom onset, and 37% of patients had good functional outcomes defined by a 3-month modified Rankin scale ≤ 2. When compared to patients with poor outcomes, the ones with favorable outcomes had lower baseline NIHSS (15 vs 7.5, p<0.01), a greater proportion of distal BAO (20% vs 63%,  p<0.01), and better posterior circulation collateral scores (5 vs 6,  p<0.01). The authors also compared these groups on a timeline of < 3hrs, 3-6 hrs, 6-12 hrs, and >12 hrs from symptom onset. Interestingly, the time to recanalization from symptom onset was not significantly different between the groups. Receptor operating characteristic (ROC) curve analysis for collateral scores yielded the highest area under the curve with a cut-off score of 6 for both BATMAN and PC-CS. Using these cut-offs, multivariate analysis revealed that NIHSS score <15 (odds ratio 8.49, P=0.004), PC-CS ≥6 (odds ratio 3.79, P=0.042), and distal BAO (odds ratio 3.67, P=0.035) were independent predictors of good clinical outcomes.

Figure 1. Schematic illustration of collateral scores.

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

Parneet Grewal, MD

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

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

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

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

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.