Endovascular intra-arterial therapy is reserved for strokes from large vessel occlusion. This article reviews the critical role of the location of the occlusion, extent and characteristics of the occlusive thrombus on noninvasive imaging, and identification of ischemic core and salvageable tissue on perfusion imaging for proper patient selection. The advantages of stentrievers over other mechanical thrombectomy approaches are discussed and the role of the aspiration thrombectomy approach in modern clinical practice is reviewed. Finally, the implications of the results of recent randomized trials of endovascular therapy on the future of intra-arterial revascularization therapies are discussed.
Key points
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Endovascular therapy should be reserved for acute strokes with large vessel occlusion confirmed by noninvasive imaging (computed tomographic [CT] angiography or magnetic resonance angiography) or catheter angiography.
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Advanced perfusion imaging helps identify patients with a favorable penumbra/ischemic core mismatch irrespective of the time of onset of stroke symptom.
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Stentrievers lead to higher recanalization rates and improved long-term clinical outcomes in patients with stroke, compared with early mechanical thrombectomy approaches.
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Enrollment of eligible patients into clinical endovascular stroke trials is critical for better understanding of the role of endovascular interventions in the treatment of acute stroke.
| ASPECTS | Alberta Stroke Program Early CT Score |
| CT | Computed tomography |
| IA | Intra-arterial |
| ICA | Internal carotid artery |
| IMS | Interventional Management of Stroke |
| IV | Intravenous |
| MCA | Middle cerebral artery |
| MR RESCUE | Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy |
| NIHSS | National Institutes of Health Stroke Scale |
| Rt-PA | Recombinant tissue plasminogen activator |
| SWIFT | Solitaire with the Intention for Thrombectomy |
| SWIFT PRIME | Solitaire FR with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke |
| SYNTHESIS Expansion | Synthesis Expansion: A Randomized Controlled Trial on Intra-Arterial versus Intravenous Thrombolysis in Acute Ischemic Stroke |
| THERAPY | Assess the Penumbra System in the Treatment of Acute Stroke |
| TICI | Thrombolysis in cerebral infarction |
| TREVO 2 | Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke |
Introduction
Each year approximately 795,000 Americans experience a new or recurrent stroke. Ischemic stroke is by far the dominant stroke type, affecting 87% of all patients (the remaining 13% of strokes are caused by intracerebral and subarachnoid hemorrhages). At present, only 3% to 4% of patients with acute ischemic stroke are treated with systemic intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA). Barriers to receiving IV thrombolysis include the public’s lack of knowledge of stroke symptoms; delay in recognizing stroke symptoms, seeking medical attention, and hospital arrival; as well as multiple contraindications to systemic administration of rt-PA.
Endovascular intra-arterial (IA) therapy is reserved for strokes from large vessel occlusion. Data from academic medical centers in the United States and Canada show that large vessel occlusion is responsible for 29% to 46% of ischemic strokes and is associated with a higher National Institutes of Health Stroke Scale (NIHSS) score, 4-fold increase in mortality, and worse neurologic outcome than other types of ischemic strokes.
According to previously published population- and epidemiology-based stroke studies, an estimated 4% to 14% of acute stroke cases (corresponding to 25,000–95,000 patients with stroke) may be eligible for endovascular stroke therapy. At present, approximately 14,000 patients undergo IA stroke interventions in the United States. The rapid evolution of endovascular stroke therapies has led to the ability to achieve successful recanalization with newer devices. The introduction of stent retriever (stentriever) technology to the arsenal of stroke neurointerventionists has led to improved clinical outcomes, making stentrievers the dominating modern thrombectomy device.
Nevertheless, the efficacy of endovascular therapy against systemic thrombolysis or standard medical therapy has yet to be proved. In recent randomized trials of IA stroke interventions that included mostly early-generation thrombectomy devices, clinical outcomes were similar between endovascular and traditional approaches to stroke treatment.
This article provides an overview of the current status of endovascular stroke interventions. The role of clot properties and advanced perfusion imaging in determining eligibility for endovascular treatment is discussed. Currently available revascularization devices and their technical characteristics are discussed. Finally, an update on ongoing and future trials of endovascular stroke therapies is provided.
Introduction
Each year approximately 795,000 Americans experience a new or recurrent stroke. Ischemic stroke is by far the dominant stroke type, affecting 87% of all patients (the remaining 13% of strokes are caused by intracerebral and subarachnoid hemorrhages). At present, only 3% to 4% of patients with acute ischemic stroke are treated with systemic intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA). Barriers to receiving IV thrombolysis include the public’s lack of knowledge of stroke symptoms; delay in recognizing stroke symptoms, seeking medical attention, and hospital arrival; as well as multiple contraindications to systemic administration of rt-PA.
Endovascular intra-arterial (IA) therapy is reserved for strokes from large vessel occlusion. Data from academic medical centers in the United States and Canada show that large vessel occlusion is responsible for 29% to 46% of ischemic strokes and is associated with a higher National Institutes of Health Stroke Scale (NIHSS) score, 4-fold increase in mortality, and worse neurologic outcome than other types of ischemic strokes.
According to previously published population- and epidemiology-based stroke studies, an estimated 4% to 14% of acute stroke cases (corresponding to 25,000–95,000 patients with stroke) may be eligible for endovascular stroke therapy. At present, approximately 14,000 patients undergo IA stroke interventions in the United States. The rapid evolution of endovascular stroke therapies has led to the ability to achieve successful recanalization with newer devices. The introduction of stent retriever (stentriever) technology to the arsenal of stroke neurointerventionists has led to improved clinical outcomes, making stentrievers the dominating modern thrombectomy device.
Nevertheless, the efficacy of endovascular therapy against systemic thrombolysis or standard medical therapy has yet to be proved. In recent randomized trials of IA stroke interventions that included mostly early-generation thrombectomy devices, clinical outcomes were similar between endovascular and traditional approaches to stroke treatment.
This article provides an overview of the current status of endovascular stroke interventions. The role of clot properties and advanced perfusion imaging in determining eligibility for endovascular treatment is discussed. Currently available revascularization devices and their technical characteristics are discussed. Finally, an update on ongoing and future trials of endovascular stroke therapies is provided.
Selection of patients for endovascular therapy
Defining the Optimal Time Window for Intervention
At present, there are 4 thrombectomy devices approved by the Food and Drug Administration under 510(k) clearance for recanalization of cerebral vessels in patients with acute ischemic stroke – the Merci Retrieval System (Concentric Medical, Mountain View, CA, USA), the Penumbra system (Penumbra Inc, Alameda, CA, USA), the Solitaire FR stentriever (ev3/Covidien Vascular Therapies, Irvine, CA, USA), and the Trevo ProVue stentriever (Stryker, Kalamazoo, MI, USA). All these devices were tested in corresponding trials that enrolled patients presenting within 8 hours of symptom onset.
Widespread use of advanced physiologic perfusion imaging technology now challenges this strict time-based selection approach. A multicenter retrospective study of 247 patients treated with endovascular therapy based on CT perfusion imaging findings, regardless of the time from stroke symptom onset, showed that IA revascularization can be safe and effective beyond the 8-h time limit in a carefully selected population. The rates of functional outcome and symptomatic intracerebral hemorrhage were similar in strokes within and beyond 8 hours from symptom onset to endovascular procedure.
Recent polling results of vascular neurologists and neurointerventionists showed a strong preference toward the use of advanced imaging in patient selection for endovascular therapy. More than two-thirds (73%) of the responders supported IA stroke interventions beyond 8 hours, and there was unanimous agreement that time-based patient selection alone is no longer the accepted standard.
Role of Noncontrast CT and Magnetic Resonance Imaging
In the initial endovascular stroke trials, noncontrast CT and magnetic resonance imaging findings were used to identify patients with early extensive strokes who would be unlikely to benefit from revascularization. Key exclusion criteria were the presence of significant mass effect with midline shift, infarction in more than one-third of the middle cerebral artery (MCA) territory, or a large infarction (>100 mL of tissue) in other vascular territories ( Box 1 ).
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Intracranial hemorrhage
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Significant mass effect with midline shift
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Infarction in more than one-third of the middle cerebral artery territory
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Infarction of greater than 50 to 100 mL of tissue (threshold depends on clinical trial or operator decision)
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ASPECTS less than 8
Abbreviation: ASPECTS, Alberta Stroke Program Early CT Score.
The Alberta Stroke Program Early CT Score (ASPECTS) can be applied to identify early ischemic changes on noncontrast CT scans using a 10-point scoring system. MCA areas with hypoattenuation or effacement of cortical sulci (10 areas total) are assigned a score of 0, and an overall low ASPECTS represents more extensive ischemia.
The application of ASPECTS to baseline noncontrast CT scans of patients enrolled in the Penumbra Pivotal Stroke Trial confirmed the validity of this score to identify patients who can benefit from endovascular therapy. Patients with an ASPECTS less than or equal to 4 showed no benefit from aspiration thrombectomy with the Penumbra system, whereas an ASPECTS greater than 7 was associated with the most benefit from revascularization.
The prognostic value of ASPECTS in the Interventional Management of Stroke (IMS) III trial (which compared combined IV thrombolysis plus IA revascularization with IV thrombolysis alone) confirmed its strong prognostic value. Patients with an ASPECTS of 8 to 10 were almost twice as likely to achieve a favorable outcome at 3 months than those with a lower score.
Perfusion Imaging
Several CT and magnetic resonance perfusion techniques have been proposed to distinguish the infarct core from the penumbra (brain tissue at risk of infarction but potentially salvageable with restoration of blood flow), each using different algorithms and perfusion maps, definitions of perfusion mismatch, and processing software packages. At present, there is no uniformly accepted perfusion protocol to quantify the extent of ischemic core and penumbra when screening potential candidates for endovascular therapy.
Perfusion-based patient selection is currently the subject of several ongoing stroke trials ( Table 1 ). The Perfusion Imaging Selection of Ischemic Stroke Patients for Endovascular Therapy (POSITIVE) trial is testing the efficacy of modern endovascular thrombectomy devices within an extended time window (0–12 hours from stroke onset) by using advanced physiologic imaging. The Solitaire FR with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial is currently testing the efficacy of IV rt-PA therapy plus Solitaire FR stentriever thrombectomy and uses CT perfusion or diffusion-weighted imaging/perfusion-weighted imaging as one of the selection criteria.
| Trial | Goal and Design | Key Perfusion-Based Selection Criteria |
|---|---|---|
| SWIFT PRIME Clinicaltrials.gov identifier: NCT01657461 | Compares combined IV rt-PA and Solitaire FR thrombectomy approach to IV rt-PA thrombolysis alone in patients with MCA M1 or ICA terminus occlusion | CT- or MRI-assessed infarct core should be <50 mL Ischemic penumbra should be >15 mL and mismatch ratio ≥1.8 Treatment should be started within 90 min of obtaining the perfusion study |
| POSITIVE Clinicaltrials.gov identifier: NCT01852201 | Compares IV rt-PA-ineligible patients presenting with either wake-up stroke or within 0–12 h of symptom onset and treated with traditional endovascular therapies (at the discretion of the neurointerventionist) vs medical therapy | CT or MR perfusion imaging per the institution standard At least 50% volume of tissue at risk and infarct core ≤35 mL |
| REVASCAT Clinicaltrials.gov identifier: NCT01692379 | Compares thrombectomy with Solitaire FR stentriever to medical therapy (standard-of-care medical therapy, including IV rt-PA) in patients with ICA or MCA M1 occlusion in patients presenting within 0–8 h of symptom onset | If stroke onset is beyond 4.5 h, favorable ASPECTS must be evaluated by CT perfusion or DWI-MRI |
In the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) trial, perfusion-based endovascular treatment with the Merci and Penumbra systems was compared with standard medical therapy. Patients were randomized for treatment within 8 hours of stroke onset after a stratification process that was based on the presence of a favorable penumbral pattern (small core and large penumbra) or an unfavorable penumbral pattern (large core and small penumbra). The study was criticized for defining an infarct core as large as 90 mL as a favorable penumbra threshold.
Other studies showed that higher infarct volume is associated with less-favorable outcomes and that an infarct core exceeding 70 mL is strongly predictive of poor neurologic outcome and an increased chance of hemorrhagic transformation in patients treated with IV thrombolysis or IA revascularization. In the MR RESCUE trial, near-complete or complete reperfusion (Thrombolysis in Cerebral Infarction [TICI] grade 2b–3) was achieved in only 27% of patients who received IA interventions and similar clinical outcomes were seen in patients irrespective of the penumbral pattern on perfusion imaging.
Modern stentriever technology, which is discussed later in this article, allows higher rates of recanalization and reperfusion than were seen in MR RESCUE. In the ongoing SWIFT PRIME trial of the Solitaire FR stentriever in acute stroke, the core infarct threshold is set at 50 mL to ensure selection of patients who may receive maximal benefit from IA therapy.
Defining IV Thrombolysis Failure
IA interventions are often considered in patients with stroke with large vessel occlusion and high NIHSS score who are eligible for and receive IV rt-PA. It is still debatable whether one can reliably predict whether a patient with stroke will have a favorable clinical outcome after IV thrombolysis or become an rt-PA-nonresponder and remain with long-term neurologic deficits. In the commonly cited National Institute of Neurological Disorders and Stroke IV rt-PA study, although no difference was seen in NIHSS score improvement between the control and IV thrombolysis arms in the first 24 hours, there was a clear benefit of IV rt-PA in lowering mortality and improving functional outcomes at 3 months. However, this original study of IV thrombolysis included strokes due to different causes and its findings do not directly reflect the efficacy of IV rt-PA for large vessel occlusion. Location of the occlusion, clot characteristics on CT imaging, and lack of immediate clinical improvement should all be taken into account when identifying patients who are unlikely to benefit from IV thrombolysis alone.
Occlusion Location and IV Thrombolysis
When estimating the likelihood of thrombolysis success with IV rt-PA, determination of the presence and the anatomic location of the large vessel occlusion is extremely important ( Box 2 ). In a multicenter study examining the likelihood of recanalization with IV rt-PA using transcranial Doppler imaging, dramatic recovery (measured as NIHSS score ≤2 at 24 hours) was seen in 33% of patients with M2 MCA occlusion and in 16% of patients with M1 MCA occlusion. None of the patients with an occlusion located at the internal carotid artery (ICA) terminus demonstrated such rapid improvement in stroke symptoms.
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Endovascular Treatment of Basilar Aneurysms
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