American Heart Association


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.

AHA Scientific Statement on Intracranial Endovascular Procedures and the Evidence Behind Them

Gurmeen Kaur, MBBS

Eskey CJ, Meyers PM, Nguyen TN, Ansari SA, Jayaraman M, McDougall CG, et al. Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association. Circulation. 2018

Endovascular intracranial procedures have seen significant advances over the past 3-4 years as reflected in all the recent stroke thrombectomy trials. Given that the last scientific review by the American Heart Association was in 2009, this Scientific Statement document updates the review of outcomes data for the efficacy and safety of these procedures and provides new recommendations for the use of these therapies.

A highly selected writing group did a computerized search of the National Library of Medicine database of literature (PubMed) from July 2007 to January 2016 to come up with these recommendations.

Is IL Receptor Antagonist an Answer to Ischemic Stroke-Related Inflammation?: A Review of the SCIL-Stroke Trial

Shashank Shekhar, MD, MS

Smith CJ, Hulme S, Vail A, Heal C, Parry-Jones AR, Scarth S, et al. SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke): A Randomized Controlled Phase 2 Trial. Stroke. 2018

Multiple preclinical and clinical research is suggesting the definite role of inflammation in the brain after ischemic stroke. The inflammation could be both detrimental and helpful based on the stages of the post-stroke pathogenesis. I always explain this to my stroke patients by giving an example of injury to, e.g., a finger. I ask them, When you hurt your finger, what happens to it? It starts hurting, swells and turns colors due to inflammation. Similarly, in the brain after stroke, the brain goes through the similar process; unlike pain medicine for fingers, we don’t have medicine which helps with inflammation in the brain, but with time, the body tends to heal most of the inflammation. Explaining to them in lay terms helps them understand the process better. In this study, investigators from the SCIL-Stroke phase II trial are investigating if blocking interleukin IL-1 results in the lowering IL-6 levels and if this could be associated with a better clinical outcome. This project is in line with the previously published work by Dr. Albers’ group, where they addressed a similar question but without a placebo control arm.

Watching Paint Dry: Do We Need to Watch tPA for 24 Hours?

Kevin S. Attenhofer, MD

Chang A, Llinas EJ, Chen K, Llinas RH, Marsh EB. Shorter Intensive Care Unit Stays?: The Majority of Post-Intravenous tPA (Tissue-Type Plasminogen Activator) Symptomatic Hemorrhages Occur Within 12 Hours of Treatment. Stroke. 2018

Over the past 20 years, use of intravenous recombinant tissue-type plasminogen activator (IV-rtPA; Actiplase) has become ubiquitous as the first-line treatment for acute ischemic stroke. Despite recent exciting advances in endovascular therapy, as well as emerging optimism about tenecteplase (TNK), IV-rtPA remains king.

IV-rtPA binds to fibrin on the surface of clot and cleaves plasminogen into plasmin. Fibrin molecules are then broken apart by the plasmin, and the clot dissolves. It is important to note that although IV-rtPA is relatively selective for clot-bound plasminogen, it still activates circulating plasminogen, thereby releasing plasmin. This can lead to the breakdown of circulating fibrinogen and cause an unwanted systemic hyperfibrinolysis. (Side note: Streptokinase and urokinase lack this specificity for clot-associated fibrin, and this is likely why they failed as therapeutic options.) I often hear practitioners cite the short half-life of IV-rtPA itself; however, they overlook the downstream effects of coagulopathy (decreased fibrinogen; increased PT, aPTT) which may persist for at least 24 hours.1

Newer Hydrogel Coils Show Promising Results for the Treatment of Small and Medium Size Intracranial Aneurysms

Sami Al Kasab, MD

Taschner CA, Chapot R, Costalat V, Machi P, Courthéoux P, Barreau X, et al. Second-Generation Hydrogel Coils for the Endovascular Treatment of Intracranial Aneurysms: A Randomized Controlled Trial. Stroke. 2018

Following the results of the ISAT trial (International Subarachnoid Aneurysm Trial), which showed better functional with endovascular treatment compared to surgical clipping, endovascular therapy became the preferred method for treating most intracranial aneurysms. Incomplete aneurysm occlusion or aneurysm recurrence, however, are among the main limitations of the endovascular approach. The use of detachable coils with or without balloon and/or stent is the most common endovascular approach treating intracranial aneurysms. Bare platinum coils are commonly used to treat intracranial aneurysms; however, given the relatively high recurrence rate, efforts have been made to evaluate the efficacy of newer generation detachable coils. Few new generation coils that aim at providing better packing and aneurysm embolization have been evaluated. Platinum coils coated with polyglycolic acid/polylactic acid polymers that provide inflammatory response at the aneurysm neck failed to prove efficacy. The use of platinum coils coated with hydrogel, which expands once in contact with liquids, leading to increased packing density, was studied in a previous trial and proved to be effective with lower rate of major recurrence; however, its use has been limited by technical limitation. In this trial (German-French Randomized Endovascular Aneurysm Trial), the authors evaluate the use of softer, second generation hydrogel coils for the treatment of intracranial aneurysms.

Therapeutic Management of Aspirin Failure – Does Changing the Antiplatelet Regimen Help?

Philip Chang, MD

Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Antiplatelet Regimen for Patients with Breakthrough Strokes While on Aspirin. Stroke. 2017

When your patient has a stroke while on an antiplatelet regimen, a common practice is to switch it. If they were on aspirin, change to clopidogrel. If on clopidogrel, one may think of switching to aspirin plus dipyridamole. While there has been much theory about aspirin failure, or aspirin resistance, there has been scant evidence to suggest that switching antiplatelet agents may benefit patients. Clinicians have switched antiplatelet regimens under the common philosophy, “Insanity is doing the same thing over and over again and expecting different results.” This is with the underlying theory that patients who experience recurrent stroke while on aspirin must have developed aspirin resistance, and blocking another antiplatelet pathway (like ADP) will confer some protective benefit. However, this theory has never been proven or disproven by a clinical study. This article by Lee et al is a great step into this clinical conundrum.

Bridging Therapy for Endovascular Thrombectomy: A Role for Direct Mechanical Thrombectomy?

Mark R. Etherton, MD PhD

Bellwald S, Weber R, Dobrocky T, Nordmeyer H, Jung S, Hadisurya J, et al. Direct Mechanical Intervention Versus Bridging Therapy in Stroke patients Eligible for Intravenous Thrombolysis. Stroke. 2017

In this entry, I discuss the matched pairs analysis of IV tPA eligible patients with large-vessel occlusion (LVO) of the anterior circulation that underwent endovascular thrombectomy (EVT) with or without pre-treatment with IV tPA.

The clinical importance of understanding the role of bridging therapy in patients with LVO is critical for efficaciously triaging this population to stroke centers. The hypothetical scenario is, how should emergency medical services appropriately triage a patient with suspicion for LVO with regards to transfer to a primary stroke center with tPA capabilities or a comprehensive stroke center with EVT capabilities that is further away? This scenario epitomizes why there is great interest in understanding the contribution that bridging therapy with tPA has on outcomes in patients with LVO of the anterior circulation.

The Role of MIST in Recanalization Times for Large Vessel Occlusion

Abbas Kharal, MD, MPH, and Richa Sharma, MD, MPH

Wei D, Oxley TJ, Nistal DA, Mascitelli JR, Wilson N, Stein L, et al. Mobile Interventional Stroke Teams Lead to Faster Treatment Times for Thrombectomy in Large Vessel Occlusion. Stroke. 2017

This retrospective analysis of the expediency of Mobile Interventional Stroke Teams (MIST) in the treatment of acute ischemic stroke (AIS) patients with large vessel occlusions (LVO) introduces an interesting method of delivering acute stroke care in a densely populated urban setting. Contrary to previously adapted AIS treatment models of drip-and-ship (transfer of patients from PSC to CSC) and mothership (transfer directly to CSC while bypassing nearby PSC), the trip-and-treat model introduces the concept of transferring the interventional team — including a neurointerventionalist attending, fellow and radiological technologist — to the PSC where the patient presents. Patients were treated by the trip-and-treat model or the drip-and-ship model based on relative availability of operating rooms and neurosurgical intensive care unit beds at the peripheral hospital and CSC. Interestingly, mean initial door-to-puncture time was shorter in the trip-and-treat model compared to the historic drip-and-ship model {143 mins vs. 222 mins, respectively (P<0.0001)}. Although there was a trend in longer puncture-to-recanalization times for trip-and-treat (P=0.0887), initial door-to-recanalization was still 79 minutes faster for trip-and-treat.

Endovascular Therapy for Stroke Can Be Translated from Ideal World to Real World

Kaustubh Limaye, MD

Mueller-Kronast NH, Zaidat OO, Froehler MT, Jahan R, Aziz-Sultan MA, Klucznik RP, et al. Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry. Stroke. 2017

It is possible to match “benchmark” workflow timings and clinical outcomes in a community setting for acute stroke patients with large vessel occlusion needing endovascular therapy.

The Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry sought to compare real-world patient workflow and outcome of patients with intracranial large vessel occlusion (LVO) requiring endovascular therapy (EVT). A total of 984 eligible patients with large vessel occlusion were enrolled at 55 different sites with an enrolling cap of 75 patients. Patients with pre-treatment modified Rankin score of 0-1, confirmed LVO, NIHSS≥8 with an intention to be treated with a Medtronic market-released neurothrombectomy device (Solitaire and Mindframe) as an initial device for stent assisted thrombectomy within 8 hours from symptom onset.

Out of 1000 patients enrolled, 16 were deemed to be screen failure resulting in intention to treat analysis of 984 patients. 64% of the patients enrolled received intravenous thrombolysis and mean NIHSS of the enrolled patients was 17. 45.2% of patients were transferred from another facility to the enrolling center. Mean distance from field to the enrolling site was 29 miles with 2/3rd of the patients <25 miles distance from enrolling site. The clinical trials for LVO needing EVT set a few important “benchmarks” for patient workflow: 1) onset to puncture time; 2) door to puncture time (DTP); 3) puncture to reperfusion time (PTR); and 4) the quality of substantial reperfusion (TICI ≥ 2b).

Administration of Statin on Acute Ischemic Stroke Patient (ASSORT) Trial

Aristeidis H. Katsanos, MD, PhD

Yoshimura S, Uchida K, Daimon T, Takashima R, Kimura K, Morimoto T, on behalf of ASSORT Trial Investigator. Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient). Stroke. 2017

Even though the role of statins in both primary and secondary stroke prevention has been well established, with a considerable number of acute ischemic stroke (AIS) patients receiving statin treatment during the first days of ictus, the usefulness of statin therapy in the acute phase of cerebral ischemia still remains debatable.

The Administration of Statin on Acute Ischemic Stroke Patient (ASSORT) Trial is a multicenter, Japanese, open-label, randomized clinical trial (RCT) with the aim to determine the efficacy of early (≤24 hours) versus delayed (7th day) statin initiation in AIS. After randomizing a total of 257 patients (early: 131, delayed: 126), authors concluded that there is no superiority of early statin administration for AIS, as no significant differences were found on the 3-month functional outcome, stroke recurrence or mortality between patients receiving early or delayed statin therapy. As highlighted by the authors, the low dose of statins that were administered in the current trial (atorvastatin 20mg/d, pitavastatin 4mg/d or rosuvastatin 5mg/d) could partially account for the aforementioned lack of efficacy, concluding that higher doses should be attested in future studies.