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Prof. Petr Widimsky ,
Acute ischemic stroke is frequently caused by thromboembolus into the middle cerebral artery. Modern stent retrievers enable effective thrombectomy. Almost half of patients may derive significant clinical benefits from thrombectomy, including complete normalization of neurologic function in some. Seven randomized trials published during the last six months have provided evidence supporting endovascular interventional treatment of acute ischemic stroke. Cardiologists are increasingly interested in acute stroke. Interventional cardiology may complement neuroradiology to cover the population needs for routine availability of acute stroke interventions. Furthermore, acute ischemic stroke is, in most cases, caused by heart disease, and treatment of underlying cardiac diseases can prevent stroke.
Acute stroke is one of the most frequent causes of death or permanent disability. For many years, stroke was regarded as an untreatable illness, a disease which could to some extent be prevented, but not effectively treated once it occurred. The first light at the end of the tunnel appeared in 1995 when the first randomized trial demonstrated benefit from thrombolytic therapy . However, despite many subsequent trials, thrombolysis failed to achieve dramatic change in stroke outcomes (over two thirds of patients did not benefit from thrombolysis) and did not influence mortality at all . Furthermore, thrombolysis has 27 contraindications in acute stroke, and thus the proportion of patients who are eligible for this therapy remains only modest.
Various endovascular procedures (mechanical clot disruption by a guidewire, intra-arterial thrombolysis, first Merci device [Concentric Medical, Mountain View, CA, USA], etc.) were tested by interventional radiologists or neurosurgeons, but none of them was proven to be superior to simple intravenous thrombolysis. It was the development of stent-retriever thrombectomy (Figure 1) a few years ago that triggered the change in this field and offered a new chance for many patients with acute stroke. However, until October 2014 there was no evidence from randomized trials that mechanical thrombectomy via the new generation stent retrievers was superior to intravenous thrombolysis alone. Furthermore, limited data were available on how to treat patients with contraindications to thrombolysis, as most previous randomized trials enrolled only lytic-eligible patients.
Figure 1. Example of a successful catheter-based thrombectomy in acute anterior stroke.
Stent retriever showing clot fragments removed.
Angiographic evidence of middle cerebral artery occlusion (red arrow) with large avascular zone (yellow elipse).
Previously occluded site appears angiographically normal (i.e., no underlying stenosis) after thrombectomy (red arrow) and rich distal vascular supply to the previously ischemic brain is restored (yellow elipse). This patient with severe stroke on admission achieved full neurologic recovery within minutes after thrombectomy.
The first randomized trial using the new generation of stent retrievers was presented in October 2014 during the stroke congress in Istanbul and was published in the first 2015 issue of the New England Journal of Medicine . Subsequently, six other randomized trials using up-to-date interventional techniques were presented early in 2015 during stroke conferences in Nashville and in Glasgow. Four of these have already been published [4-7]; publication of the last two is pending. One common and very important feature of most of these trials was the inclusion of patients both eligible and ineligible for thrombolysis, with the exception of the SWIFT PRIME trial which enrolled only patients eligible for thrombolysis. These recent trials reflect real life better than most previous trials, which excluded lytic-ineligible patients, and also provide evidence on how to treat these patients. Similar principles were applied in these trials: both treatment arms included all ischemic stroke patients (those receiving intravenous [IV] tPA within <4.5 hours, those with contraindications for tPA, and/or those presenting after 4.5 hours) as long as they fullfilled other pre-specified criteria. In other words, current guideline-recommended therapy (IV tPA whenever indicated or conservative treatment when tPA not indicated) was compared to catheter-based intervention (with or without previous “bridging“ thrombolysis). Table 1 summarizes the most important available information from these trials. Figure 2 shows graphically the relative benefits achieved with different treatment strategies in acute ischemic stroke.
These new trials led to the immediate update of the stroke guidelines . Table 2 summarizes the most important recommendations from these new guidelines.
Table 1. Randomized trials comparing catheter-based thrombectomy on top of standard treatment (including thrombolysis whenever indicated) versus standard treatment alone.
Total number of patients enrolled
Median NIHSS at baseline
Penumbra imaging used for patient selection
Yes (CT perfusion in all pts)
Yes (in 81% of pts)
Stroke onset - randomization
Stroke onset – tPA/CBI start time
Stroke onset – reperfusion time in the group with intervention
Stent-retriever use (intervention group)
Carotid stenting in the acute phase
General anesthesia use
Reperfusion (TICI grade 2b or 3)
Favourable neurologic outcome (mRS 0-2 at 90 days) in the intervention group
Favourable neurologic outcome (mRS 0-2 at 90 days) in the control group
Symptomatic intracerebral hemorrhage (intervention group)
Early mortality (7 days) in the intervention group
Late mortality (90 days) in the intervention group
18.9% (30 days)
*Data from THERAPY and THRACE trials are preliminary as presented during the Stroke Conference in Glasgow, 2015. These two trials have not been published as yet.
Figure 2. Graph showing improved acute stroke outcomes with modern therapies.
Moderate-to-severe ischemic stroke patients without reperfusion treatment have extremely poor outcomes: only about 15% reach functional independence (mRS 0, 1 or 2), while the remaining 85% either die or remain severely and permanently disabled. Thrombolysis improved this significantly, and further improvement was achieved with catheter-based thrombectomy. Nevertheless, despite the best current therapy, over 50% of patients with this type of stroke remain severely disabled. This can be further improved only by a large change of the entire system, whereby all stroke patients should present very early (within 1 hour) to comprehensive stroke centers for immediate reperfusion therapy. mRS: modified Rankin scale, values 0-2 mean functional independence after 3 months.
Table 2. The new recommendations from the AHA/ASA stroke guidelines .
Catheter-based intervention for acute stroke uses guiding catheters (frequently with distal-tip balloons for proximal protection during thrombus retrieval), microcatheters with 0.010“ or 0.014“ guidewires (for selective cannulation of the occluded artery), distal aspiration (distal access) catheters with an extremely soft tip (for direct thrombus aspiration), stent retrievers (for immediate flow restoration and thrombus retrieval), small-size dilatation balloons (for rather rare intracranial stenosis dilatation), carotid dilatation balloons (for internal carotid dilatation – some operators prefer this approach in the acute phase of stroke rather than acute carotid stenting), distal protection devices (during carotid interventions – however, their role in the acute stroke setting is not well established), carotid stents (most operators prefer acute carotid stenting over balloon dilatation alone when stroke is caused by carotid occlusion), coronary stents (in very rare situations like vertebral artery stenosis), etc. Obviously, the most important of these are stent retrievers, for immediate flow restoration (during their expansion within the thrombosed segment) and subsequent thrombus extraction. To decrease the risk of thrombus fragmentation with distal embolization to a new territory (and subsequent stroke progression), simultaneous proximal occlusion of the carotid artery by a balloon guide and powerful aspiration achieving reversed flow are recommended.
Acute ischemic stroke should be treated as a super emergency. Certain endovascular procedures have been shown to provide clinical benefit in selected patients with acute ischemic stroke. Systems of care should be organized to facilitate the delivery of this care .
We suggest the following optimal logistics and sequence of steps:
The key factor is that some processes run in parallel to save time: while the patient is arriving at theCT suite and the CT is done and read, the cathlab and an interventionalist should simultaneously be made available (i.e., not beginning a new procedure, quickly finishing the current procedure, etc.). Such an approach may save 30-60 minutes of time between CT and groin puncture: this time may be critical in deciding whether the patient will recover or will die/remain disabled. Some unnecessary cathlab alerts (when intervention is not indicated after CT) are a reasonable price to pay for this approach.
Today, given the superior benefits of endovascular intervention, the whole structure of acute stroke care needs to be reorganized to meet patient needs and to deliver evidence-based treatments effectively. However, a blueprint for success with novel stroke treatments should be composed of numerous elements and requires the efforts of various parties. Regional and national plans for covering a whole population with 24/7 adequate acute stroke care are necessary in close cooperation with professionals and decision-makers. New European-wide training programs for expert physicians in stroke care should be initiated shortly. The European Stroke Organisation has a unique role in providing expertise, consultation, guidelines, and versatile training to meet new demands in stroke care .
Cardiologists should broadly cooperate with neurologists in stroke prevention (both primary and secondary) due to the fact that most strokes occur as a complication of another cardiovascular disease (e.g., atrial fibrillation, hypertension, endocarditis, intracardiac shunts, etc.). In some regions (where neuroradiology services are not available for acute stroke patients on a 24/7 basis), interventional cardiologists may successfully fill this gap and, after specific training, achieve similar outcomes to their neuroradiology colleagues [10,11].
Acute ischemic stroke is a catastrophic cardiovascular disease, frequently with cardiac causes and cerebral consequences. Thus, close cooperation between neurologists and cardiologists is necessary for optimal patient management. Interventional cardiology with its widespread non-stop services for acute myocardial infarction can fill the existing gaps in coverage of population needs with neurointerventional services. A new medical subspecialization may soon emerge - neurocardiology or cardioneurology [12,13].
Patients should receive endovascular therapy with a stent retriever if they meet all the
(a) prestroke mRS score 0-1,
(b) intravenous r-tPA within 4.5 hours of onset
(c) occlusion of the internal carotid artery or proximal MCA (M1),
(d) age ≥18 years,
(e) NIHSS score of ≥6,
(f) ASPECTS of ≥6,
(g) groin puncture within <6 hours of symptom onset
When treatment is initiated beyond 6 hours from symptom onset, the effectiveness of
endovascular therapy is uncertain for patients with acute ischemic stroke who have
causative occlusion of the internal carotid artery or proximal MCA (M1). Additional randomized trial data are needed.
In carefully selected patients with anterior circulation occlusion who have
contraindications to intravenous r-tPA, endovascular therapy with stent retrievers
completed within 6 hours of stroke onset is reasonable.
Although the benefits are uncertain, use of endovascular therapy with stent retrievers may be reasonable for carefully selected patients with acute ischemic stroke in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset and who have causative occlusion of the M2 or M3 portion of the MCAs, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries.
Endovascular therapy with stent retrievers may be reasonable for some patients <18 years of age with acute ischemic stroke who have demonstrated large vessel occlusion in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset, but the benefits are not established in this age group.
Although the benefits are uncertain, use of endovascular therapy with stent retrievers may be reasonable for patients with acute ischemic stroke in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset and who have prestroke mRS score of >1, ASPECTS <6, or NIHSS score <6 and causative occlusion of the internal carotid artery or proximal MCA (M1).
Observing patients after intravenous r-tPA to assess for clinical response before pursuing endovascular therapy is not required to achieve beneficial outcomes and is not recommended.
The use of mechanical thrombectomy devices other than stent retrievers may
be reasonable in some circumstances.
The use of proximal balloon guide catheter or a large bore distal access catheter rather than a cervical guide catheter alone in conjunction with stent retrievers may be beneficial. Future studies should examine which systems provide the highest recanalization rates with the lowest risk for nontarget embolization.
The technical goal of the thrombectomy procedure should be a TICI 2b/3 angiographic result to maximize the probability of a good functional clinical outcome.
Use of salvage technical adjuncts including intra-arterial fibrinolysis may be
reasonable to achieve these angiographic results, if completed within 6 hours of symptom onset.
Angioplasty and stenting of proximal cervical atherosclerotic stenosis or complete
occlusion at the time of thrombectomy may be considered but the usefulness is unknown.
Endovascular therapy with stent retrievers is recommended over intra-arterial fibrinolysis as first-line therapy.
It might be reasonable to favor conscious sedation over general anesthesia during
endovascular therapy for acute ischemic stroke. However, the ultimate selection of
anesthetic technique during endovascular therapy for acute ischemic stroke should be
individualized based on patient risk factors, tolerance of the procedure, and other clinical characteristics. Randomized trial data are needed.
This year (2015) is a historical landmark in acute stroke treatment. Sufficient evidence from multiple randomized trials has resulted in significant guideline modifications, with catheter-based endovascular therapy becoming a class IA indication for all patients with acute ischemic stroke caused by a major artery occlusion, provided that they present sufficiently quickly to the healthcare system. The widespread implementation of this new treatment strategy will require significant changes in the organization of care and effective interdisciplinary cooperation, involving neurologists, radiologists, neurosurgeons, cardiologists and other specialists.
Petr Widimský, MD, DrSc, FESC,
Professor of Medicine
Cardiocenter, Third Faculty of Medicine, Charles University Prague
and University Hospital Kralovske Vinohrady Prague
100 34 Prague 10
Conflict of interest: No conflict of interest related to this manuscript.
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