American Heart Association

treatment

Better is the Enemy of Good

Elena Zapata-Arriaza, MD
@ElenaZaps

García-Tornel A, Requena M, Rubiera M, Muchada M, Pagola J, Rodriguez-Luna D, et al. When to Stop: Detrimental Effect of Device Passes in Acute Ischemic Stroke Secondary to Large Vessel Occlusion. Stroke. 2019;50:1781–1788

The achievement of mTICI 3 after one pass, known as first pass effect, is clearly associated with better functional outcome, as compared with those patients with more passes needed to obtain full recanalization. But how many passes should we attempt before stop procedure? Or maybe we should pursue a good (TICI 2B) but not perfect recanalization, instead of seeking TICI 3, because such recanalization is more than enough for patient outcome?

These are some of the aims of this study, in addition to finding the relation between number of passes and recanalization degree and clinical outcome.

Article Commentary: “Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow”

Yan Hou, MD, PhD

Bornstein NM, Saver JL, Diener HC, Gorelick PB, Shuaib A, Solberg Y, et al.. Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow. A Randomized, Sham-Controlled Trial. Stroke. 2019;50:00-00.

Preclinical studies have demonstrated that sphenopalatine ganglion (SPG) stimulation is a potent method to enhance collateral flow and reduce infarct size in stroke animal models. The ImpACT-24A Investigators performed a sham-controlled, randomized trial to test the efficacy and safety of SPG stimulation as a potential therapy for patients with acute anterior circulation ischemic stroke who are not eligible for reperfusion therapy.

A total of 253 patients with acute anterior circulation ischemic stroke with moderate deficit (median NIHSS of 11) within 24 hours of onset not treated with tPA or thrombectomy either received SPG (n=153) or sham (n=100) stimulation. The primary efficacy outcome is mRS improvement beyond expectation at 90 days, which was defined as an mRS score one or more points better than expected based on a prognostic model. Although SPG stimulation only showed a 9.7% higher rates of mRS improvement beyond expectations in the intention to treat population (SPG vs. sham: 49.7% vs. 40%, odd ratio 1.48, p=0.13); there was a 23% higher rate of mRS improvement beyond expectations in the subgroup of patients with confirmed cortical involvement (SPG vs. sham: 50% vs. 27%, odd ratio 2.7, p=0.03). The different beneficial effects of SPG stimulation between patients with cortical infarcts and deep subcortical infarcts was considered due to more robust collateral arterial networks in superficial leptomeningeal arteries supplying the cortical layers. SPG stimulation was not associated with any increase in serious adverse events, symptomatic intracranial hemorrhage, or mortality. Only two serious adverse events were considered possibly related to the implantation (one epistaxis and one torn extraction).

Antiplatelet Therapy in Stroke: The Old and the New

Alan C. Cameron, MB ChB, BSc (Hons), MRCP

Hackam DG, Spence JD. Antiplatelet Therapy in Ischaemic Stroke and Transient Ischaemic Attack. Stroke. 2019; 50:773–778.

Antiplatelet therapy reduces the burden of recurrent vascular events in patients with non-cardioembolic ischaemic stroke or TIA and the authors present an overview of major trials.  The IST and CAST studies, conducted over 20 years ago, highlight the benefits of aspirin in the acute setting and the benefits of aspirin in the longer term are demonstrated by the Antithrombotic Trialists’ Collaboration.  It was later shown that aspirin and dipyridamole in combination is more effective than aspirin alone, with most data coming from the ESPS-2 and ESPRIT studies, although dipyridamole requires twice daily dosing and many patients develop headache.  The PRoFESS trial shows rates of recurrent stroke are similar with clopidogrel compared to aspirin and dipyridamole, although clopidogrel has once-daily dosing and fewer patients develop headache.

The landmark CHANCE and POINT trials demonstrate that DAPT with clopidogrel and aspirin reduces the risk of stroke and vascular events in patients with high-risk TIA or minor stroke compared to aspirin alone and the benefit is confined to the early period.  This may explain why longer-term trials of DAPT (MATCH, SPS3 and CHARISMA) found no benefit. The SOCRATES trial found that DAPT with ticagrelor and aspirin is not superior to aspirin in reducing vascular events, although ticagrelor shows a strong trend toward reduced stroke in the acute setting and is more efficacious in patients with large artery disease or patients already taking aspirin.  The THALES trial is studying ticagrelor in this context and will help to better define the role of ticagrelor in acute stroke. Importantly, we can reduce the risk of haemorrhage associated with antiplatelet therapy by effectively managing bleeding risk factors, including blood pressure control, treatment of Helicobacter pylori infection and proton pump inhibitors for high risk patients.

Intervening on Interventions in Endovascular Stroke Treatment

Raffaele Ornello, MD

Janssen PM, Venema E, Dippel DWJ. Effect of workflow improvements in endovascular stroke treatment: A systematic review and meta-analysis. Stroke. 2019;50:665–674.

Acting fast is of key importance to ensure the success of endovascular treatment (EVT) for ischemic stroke. While the available evidence already showed that workflow interventions improve the time to treatment with intravenous rtPA, the effect of workflow interventions on EVT is less clear. In their systematic review and meta-analysis, the authors included 51 studies referring to workflow interventions in EVT, including anesthetic management, pre-hospital management, in-hospital transfer management, teamwork, and feedback. Overall, each single intervention resulted in a significant improvement of time to EVT, with a mean value of 26 minutes and up to 64 minutes for feedback interventions.

Although limited by the large contribution of retrospective data and by the low availability of pre-hospital management data, the published systematic review and meta-analysis underlines the importance and effectiveness of planning adequate EVT workflow intervention in clinical practice to improve the treatment time of ischemic stroke and patient outcomes.

Tandem Lesions: To Stent or Not To Stent?

Robert W. Regenhardt, MD, PhD
@rwregen

Jadhav AP, Zaidat OO, Liebeskind DS, Yavagal DR, Haussen DC, Hellinger FR, et al. Emergent Management of Tandem Lesions in Acute Ischemic Stroke: Analysis of the STRATIS Registry. Stroke. 2018;50:428–433.

With the 2015 trials irrefutably showing the superiority of endovascular thrombectomy (ET) over intravenous tPA alone for the treatment of stroke secondary to large vessel occlusion (LVO), and the 2018 trials showing it may be effective for up to 24 hours from symptom onset, current research efforts focus on expanding the number of patients who may be eligible for this highly effective treatment (e.g., larger core, more distal occlusions) and optimizing protocols for more complex cases. The latter is exemplified by questions that remain about the best approach to treating tandem lesions, which involve both the cervical internal carotid artery (ICA) and an intracranial artery. The most common etiology is cervical ICA atherosclerosis, but tandem lesions can also result from cervical ICA dissection.

Perhaps the biggest conundrum in the management of tandem lesions is whether or not to stent the cervical ICA in the acute setting. Given the risk of dual antiplatelet therapy, especially in patients who received tPA and have larger cores, some interventionalists choose to defer in the acute setting and offer stenting versus endarterectomy later. If stenting is offered in the acute setting, it is unclear whether cervical ICA stenting should be done before or after intracranial ET. Furthermore, the role of angioplasty and the optimum antithrombotic regimen have yet to be determined. There is limited data available to help guide these decisions. While many of the ET trials included patients with tandem lesions, the management was highly variable. Tandem lesions were present in 32% of MR CLEAN, 18% of REVASCAT, and 17% of ESCAPE, while they were excluded from SWIFT PRIME and EXTEND IA. An analysis of the 30 patients with tandem lesions that were treated with ET in ESCAPE showed 17 underwent cervical ICA stenting, 10 before and 7 after intracranial ET. Of the 13 for which stenting was deferred in the acute setting, only 4 underwent ICA revascularization later.

Evaluation and Treatment Issues of a Cancer-Related Stroke Patient

Lina Palaiodimou, MD

Neilson LE, Rogers LR, Sundararajan S. Evaluation and Treatment of a Patient with Recurrent Stroke in the Setting of Active Malignancy. Stroke. 2018

This article by Neilson et al. reports a case of a 75-year-old female patient presenting with multiple ischemic lesions with temporal dispersion and localization in multiple arterial territories. The patient was newly diagnosed with lung cancer, more specifically mucinous adenocarcinoma, found randomly in MRI of cervical spine, which was performed as part of differential diagnosis of transient left arm weakness and numbness. Smoking was reported as a predisposing factor for lung cancer, as well as ischemic stroke.

NAVIGATE Through the Current Treatment Options in Secondary Stroke Prevention of ESUS Patients with Patent Foramen Ovale

Aristeidis H. Katsanos, MD, PhD

Kasner SE, Swaminathan B, Lavados P, Sharma M, Muir K, Veltkamp R, et al. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial. Lancet Neurol. 2018

NAVIGATE ESUS was a double-blinded, randomized, phase 3 clinical trial comparing rivaroxaban 15mg to aspirin 100mg in the secondary stroke prevention of patients with embolic strokes of undetermined source (ESUS). In the present pre-specified subgroup analysis, NAVIGATE ESUS Investigators assessed further the safety and efficacy of rivaroxaban 15mg to aspirin 100mg in ESUS patients with patent foramen ovale (PFO). PFO was uncovered in a total of 534 patients (7.4% of the total NAVIGATE ESUS trial population) after investigation with either transthoracic or transesophageal echocardiography.

After a mean follow-up of 11 months, ESUS patients with PFO randomized to rivaroxaban treatment were found to have a half, although non-statistically significant, risk for stroke recurrence compared to ESUS patients with PFO randomized to aspirin treatment (hazard ratio=0.54; 95%CI: 0.22–1.36). Interestingly, the treatment effect of rivaroxaban was found to be more pronounced in patients over 60 years of age, which were excluded from the majority of trials on PFO closure. However, rivaroxaban treatment was associated with a double, although again non-statistically significant, risk of major bleeding compared to aspirin (hazard ratio=2.05; 95% CI: 0.51–8.18).

When More Isn’t More: Increasing Stent Retriever Passes Associated with Futile Recanalization

Kat Dakay, DO

Baek J-H, Kim BM, Heo JH, Nam HS, Kim YD, Park H, et al. Number of Stent Retriever Passes Associated With Futile Recanalization in Acute Stroke. Stroke. 2018

Mechanical thrombectomy has been recognized as the standard of care in acute ischemic stroke due to proximal large vessel occlusion. However, despite best efforts, it is not always successful: According to the authors, about 20-30% of clots are refractory to stent retriever thrombectomy. However, even if the vessel is eventually recanalized, the patient may still not necessarily have a favorable outcome, often termed “futile recanalization”; rates of futile recanalization vary widely depending on the definition used. Additionally, there are risks to a long and complex thrombectomy procedure in cases with refractory clots. In this article, the authors examine the number of stent retriever attempts, or passes, as a marker for futile recanalization.

In this multicenter, retrospective study [1], patients with a proximal anterior circulation large vessel occlusion treated with stent retriever thrombectomy were included. Additionally, patients needed to have an NIHSS of 4 or greater and be treated within 10 hours of last known well. The number of stent retriever passes required to achieve successful recanalization of TICI 2b or 3 was measured. A total of 467 patients were included in the study, with a median age of 67.3 years, median NIHSS of 15, and median ASPECTS of 8. The median number of stent retriever passes was 2, although rates ranged from 1 to 7.

Transcranial Stimulation for Aphasia Recovery in Subacute Stroke Patients

Danielle de Sa Boasquevisque, MD

Spielmann K, van de Sandt-Koenderman WME, Heijenbrok-Kal MH, Ribbers GM. Transcranial Direct Current Stimulation Does Not Improve Language Outcome in Subacute Poststroke Aphasia. Stroke. 2018

Trancranial direct current stimulation (tDCS) is a non-invasive neuromodulation therapy with the potential to enhance recovery after ischemic stroke. This technique uses a weak electrical current that ultimately leads to a polarity specific change in excitability: increasing cortical excitability (anodal tDCS), decreasing cortical excitability (cathodal tDCS), or a combination of both effects (bihemispheric). Many studies demonstrated benefit in chronic aphasia, but research within the early phase after stroke, when the mechanisms of neuroplasticity are more active, are still scarce.

In this article, the authors aimed to investigate the effects of online anodal tDCS applied over the left inferior frontal gyrus on aphasia recovery in the subacute phase after stroke. This study was a multi-center double-blinded clinical trial that enrolled patients with aphasia after ischemic or hemorrhagic stroke between 3 weeks and 3 months poststroke. Participants were randomized to 2 parallel groups: anodal tDCS (1mA, 20 minutes) and sham tDCS. They also received online tDCS while on 2 weeks (5 sessions/week) of 45-min word-finding language therapy session.

Alteplase in Minor Stroke: A Daily Dilemma

Alejandro Fuerte, MD

Levine SR, Weingast SZ, Weedon J, Stefanov DG, Katz P, Hurley D, et al. To Treat or Not to Treat? Exploring Factors Influencing Intravenous Thrombolysis Treatment Decisions for Minor Stroke. Stroke. 2018

The activase/alteplase package insert from the Food and Drug Administration was updated in February 2015. Despite this, controversy continues over the criteria for the use of this drug in minor stroke, defined as National Institutes of Health Stroke Scale (NIHSS) score 1 to 5. In this article, Levine et al explore clinical factors influencing alteplase treatment decisions for patients with ictus minor.

This is a descriptive study. A committee of stroke experts identified the key factors in making decisions about the use of alteplase. The most prominent factors on the basis of which the study was developed were the following: all patient-dependent: National Institutes of Health Stroke Scale (NIHSS), NIHSS area of primary deficit, baseline functional status, previous ischemic stroke (IS), previous intracerebral hemorrhage (ICH), recent anticoagulation, and temporal pattern of symptoms in first hour of care. A fractional factorial design was used to provide unconfounded estimates of the effect of the 7 main factors, plus first-order interactions for the NIHSS. A joint statistical analysis was then applied.