American Heart Association

treatment

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.

Which Hemostatic Agents Should We Use in Acute ICH?

Hatim Attar, MD

Law ZK, Salman RA, Bath PM, Steiner T, Sprigg N. Hemostatic Therapies For Acute Spontaneous Intracerebral Hemorrhage. Stroke. 2018

There are various strategies to tackle acute Intracerebral Hemorrhage (ICH) with intent to minimize the risk of hematoma expansion and preserve brain perfusion. These have been areas of interest for decades with ongoing research and regular updates in management. In today’s Neuro-Intensive care units, one increasingly encounters patients who are on various antiplatelet (AP) and anticoagulant (AC) agents. These agents, without a doubt, are implicated with spontaneous ICH and subsequent hematoma expansion, too. This review has addressed the burning question: Which hemostatic therapies should be used in spontaneous ICH in the setting of antithrombotic agents?

The authors searched multiple databases and reviewed all available international trials until November 2017. They included randomized controlled trials (RCTs) which evaluated any hemostatic intervention for acute spontaneous ICH. A total of 12 RCTs were found relevant and included in this review, which amounted to a total of 1732 participants. 7 RCTs, involving 1480 participants, were on administration of clotting factors, 3 RCTs with 57 participants on antifibrinolytic drugs, 1 RCT with 190 participants on platelet transfusion, and another 1 RCT with 5 participants on clotting factors vs. fresh frozen plasma. RCTs which used aggregated data for ICH, not differentiating spontaneous hemorrhages from others, were excluded.

By |September 17th, 2018|clinical, treatment|0 Comments

Thrombectomy in Acute Stroke with TANdem Lesions: TITANic Technical Challenge?

Robert W. Regenhardt, MD, PhD

Gory B, Piotin M, Haussen DC, Steglich-Arnholm H, Holtmannspötter M, Labreuche J, et al. Thrombectomy in Acute Stroke With Tandem Occlusions From Dissection Versus Atherosclerotic Cause. Stroke. 2017

The revolution of acute stroke care, with the 2015 trials demonstrating superiority of endovascular thrombectomy (ET) compared to tPA alone and the subsequent DAWN and DEFUSE 3 trials extending its time window, has raised many questions about which patients will experience net benefit from this powerful therapy. Certainly, some vessel occlusions are more amenable to ET than others, but should the presence of technically difficult occlusions, with perhaps higher procedural risks, limit eligibility? Though poorly represented, patients with anterior circulation tandem lesions, involving both the cervical internal carotid artery (ICA) and an intracranial artery, experienced similar benefits as those with isolated intracranial occlusions in the HERMES meta-analysis. It is unclear if the etiology of tandem lesions predicts outcomes, if etiology should influence the decision to undergo ET, or if it should influence the procedural approach.

The two most common etiologies of tandem lesions are carotid atherosclerosis and carotid dissection. Treatment typically occurs in two phases: management of the cervical ICA lesion by stenting, angioplasty, both, or medical treatment alone, and management of the intracranial occluded vessel by stent retriever or direct aspiration first pass technique. The order of these phases remains controversial, with some centers starting with the intracranial lesion as stent retrievers only require a small microcatheter for deployment. Stenting versus angioplasty of the cervical ICA can be debated based on adequacy of collaterals, risk of reperfusion injury, risk of immediate dual antiplatelet therapy, and other individualized factors.