Catheter-based thrombectomy for acute ischemic stroke

BACKGROUND

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 [1]. 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 [2]. 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.

Randomized trials published in 2015 and subsequent guideline changes

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 [3]. 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 [8]. 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.

*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 [8].

Techniques

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.

Logistics

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 [8].

We suggest the following optimal logistics and sequence of steps:

1. Population awareness of the symptoms of stroke and the critical importance of time.
2. Witness(es) of acute stroke onset should immediately (within minutes) call emergency medical services (EMS). Patients with moderate-to-severe stroke are usually not able to do it themselves!
3. EMS should consider suspected stroke as an emergency similar to a car accident or acute myocardial infarction. When stroke suspicion is confirmed during the first medical contact (FMC), EMS should alert the nearest stroke center (hospital with adequate specialized departments, capable of imaging, thrombolysis and interventions).
4. Even at this stage (before patient arrival to the hospital) the neurologist and the interventionalist should be informed about a potential acute stroke patient (the interventionalist and angio suite should be available, if necessary, within the next 30 minutes).
5. EMS should transfer the patient to the emergency room where CT is available (to avoid secondary transfers within the hospital).
6. The neurologist should meet the patient in the CT suite and immediately read the CT with the radiologist.
7. Confirmation of the indication for catheter intervention (cathlab preparation finalized).
8. Possible IV thrombolysis initiation at the CT suite (to avoid any unnecessary transfers from CT to ICU and then from ICU to cathlab).
9. Direct transfer from CT to cathlab.
10. Catheter intervention.
11. Transfer to neurology ICU (stroke unit).

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 [9].

The role of cardiologists in stroke

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].

Table 2. The new recommendations from the AHA/ASA stroke guidelines [8].

CONCLUSION

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.