Acute ischemic stroke (AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, but key limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy.

The annual incidence of stroke in the United States is approximately 795000[1]. Stroke is the second leading cause of lost disability-adjusted life-years in high-income countries and the second most common cause of mortality worldwide[2,3]. Approximately 80% of strokes are ischemic and 20% are hemorrhagic[4]. Acute ischemic stroke (AIS) is caused by a focal interruption of cerebral blood flow, most commonly due to occlusion of a major cerebral artery by local thrombosis or embolus. The resulting ischemia leads to tissue damage through a complex pathophysiological response of excitotoxicity, peri-infarction depolarization, inflammation and apoptosis[5].

The goal of therapy for AIS is to achieve cerebral reperfusion before neurological damage becomes irreversible. The correlation between vessel recanalization and favorable neurological outcome is well-studied[6,7], although additional factors such as stroke severity and age are also likely to have a significant impact on clinical outcome[8,9]. Currently, the only FDA-approved treatment with level 1 evidence for AIS is intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (alteplase) within three hours of symptom onset[10]. Additional trials have demonstrated that extending this time window to 4.5 h is beneficial in appropriately selected patients[11,12]. However, few patients (< 10%) meet eligibility criteria for this therapy[13-15]. Additionally, larger and more proximally-located thrombi may be relatively resistant to IVT[16-21]. Successful recanalization of large vessel occlusion (LVO) with IVT alone is infrequent, ranging from 10% in internal carotid artery (ICA) occlusions to 30% in middle cerebral artery occlusions, and IVT is associated with a risk of systemic and intracerebral hemorrhage (ICH)[22].

These limitations have led to the exploration of alternative or complementary treatment approaches for AIS. Endovascular mechanical thrombectomy has developed over the past decade as a safe and effective intervention. Rapid advancement in catheter-based and endovascular device technology has led to an increasing number of patients with AIS being treated when IVT is ineffective or contraindicated[14]. Here, we review the evolution of endovascular mechanical thrombectomy devices for the treatment of AIS.

Endovascular treatment of AIS began with intra-arterial (IA) infusion of thrombolytic agents. Several studies investigating these therapies reported favorable rates of vessel recanalization and neurological outcomes[23-25]. Given the relatively favorable risk to benefit profiles of current mechanical thrombectomy devices, IA thrombolysis is infrequently used in modern endovascular AIS therapy. This was followed by the implementation of balloon angioplasty and microwire techniques to mechanically disrupt thromboemboli[26,27]. Additionally, intracranial stents were shown to be effective at restoring blood flow when deployed within an occluded vessel[28,29].

Endovascular retrieval devices were first developed to recover errant coils and other foreign bodies that had embolized within the cerebral circulation during endovascular procedures[30-32]. The development of devices to remove occlusive thromboemboli was thus a natural extension of pre-existing technology. Endovascular mechanical thrombectomy involves physical extraction of the thrombus through a catheter. Due to the anatomical limitations imposed by vascular anatomy on currently available thrombectomy catheters, thrombi in large ICA, the Circle of Willis and the first two branches of the anterior (A1 and A2), middle (M1 and M2) and posterior (P1 and P2) cerebral arteries) are the most readily accessible. Smaller branches of the cerebral circulation are often too narrow and tortuous to undergo successful mechanical thrombectomy.

Alternative treatment methods for strokes from LVO are an important development, as medical management is often unsuccessful, and these strokes are associated with high rates of morbidity and mortality[25]. The two main methods of endovascular mechanical thrombectomy for LVO include: (1) physical grasping and removal of thrombi with retrieval devices and (2) aspiration of occlusive thrombi with suction devices (Table 1).

The Merci Retriever (Concentric Medical, Mountainview, CA) was FDA-approved in August 2004 as the first clot retriever device in the United States. This device utilizes memory shaped nitinol (nickel titanium) material to convert from a straight to helical configuration to grasp the thrombus. In this procedure[33]: (1) the retriever is advanced through the thrombus in its straight configuration; (2) two to three helical loops are deployed beyond the thrombus; (3) the device is retracted to contact the thrombus, and proximal loops are deployed within the thrombus; (4) a balloon guide catheter located in the common or internal carotid artery is inflated to control intracranial blood flow; and (5) three to five clockwise rotations are performed to fully ensnare the thrombus, and the Merci Retriever-thrombus complex and microcatheter are removed together.

The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial was a prospective, non-randomized, multicenter trial that first evaluated this device[34]. Recanalization, defined as Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3 flow in all treatable vessels, was achieved in 48% (68/141) of patients. Patients with recanalization had better neurological outcomes (P < 0.0001), as determined by modified Rankin Score (mRS) of 2 or less at 90 d, and lower mortality rates (P = 0.01) than those without recanalization, and procedure-related complication and symptomatic ICH rates were comparable to trials of IV t-PA, combined IV/intra-arterial t-PA, and intra-arterial prourokinase[10,25,35].

Newer device generations (Figure 1) have moderately improved rates of recanalization[36]. One such advancement was the Distal Access Catheter (DAC; Concentric Medical) in 2008. The DAC has a flexible distal shaft that facilitates its navigation around the anterior genu of the ICA, beyond the origin of the ophthalmic artery[37]. This improved the navigation of the Merci Retriever through the carotid siphon with each pass, improving procedural efficiency.

Open in New Tab   Full Size Figure   Download Figure

Figure 1 Timeline of FDA approval, release dates and randomized controlled trials of endovascular mechanical thrombectomy devices.

The Penumbra System (PS) (Penumbra Inc., Alameda, CA) was FDA-approved in December 2007 and utilizes aspiration for thrombus extraction. In this procedure[38]: (1) the PS catheter is advanced through a guide catheter to a point just proximal to the occlusion; (2) a microwire called a separator is repeatedly passed through the thrombus in order to fragment the clot; and (3) constant suction is applied to the PS catheter to aspirate the thrombus fragments.

The PS was evaluated in a prospective, multicenter study of 125 patients with National Institute of Health Stroke Scale (NIHSS) score ≥ 8 who were ineligible for or refractory to IVT[38]. Recanalization (TIMI ≥ 2) was achieved in a high proportion (81.6%) of patients without significantly different complication rates than those seen in the MERCI trials. Good clinical outcome (mRS ≤ 2) was observed in 25% of patients at 30-d follow-up. More recent generations of the PS include the 054 Reperfusion catheter (2009) and the MAX Reperfusion catheter line (2011). These devices achieve greater aspiration force due to larger proximal lumens[39]. The 054 Reperfusion device was found to accomplish recanalization at a median time of 20 min[40], significantly less than the median time of 45 min reported in the penumbra pivotal trial using previous generation technology.

Stentrievers utilize a retrievable stent to engage and remove the thrombus. In this procedure[41]: (1) the stentriever is advanced within a microcatheter through the thrombus until it is a few millimeters distal to the clot; (2) the stent is deployed, incorporating the thrombus into the stent struts and displacing it radially to the vascular wall; and (3) after three to five minutes, the microcatheter and stentriever are removed together under continuous proximal aspiration with a syringe. This must be performed cautiously, as at least one case of intracranial extravasation during device withdrawal has been reported[42]. It is also possible to perform a control angiogram while the stentriever is deployed, which can confirm flow restoration. However, since this may promote distal migration of thrombus fragments, the utility of performing an angiogram during stentriever deployment is controversial.

The MAX reperfusion catheters allowed for the development of direct aspiration as an additional thrombectomy technique. Direct suction can be applied from the PS device or a syringe plunger connected to the proximal hub of the catheter. Previously, this technique was limited by the challenges of tracking an aspiration catheter through the intracranial circulation, but the improved trackability of the MAX reperfusion catheters has facilitated its development[37]. Furthermore, these catheters can still be used in combination with other endovascular devices. The ADAPT technique[52] is an increasingly utilized approach which combines modern aspiration and retrieval technology. Direct aspiration with a large bore aspiration catheter (commonly MAX reperfusion system) is first performed. If direct aspiration fails, stentrievers, balloons and stents can be still be passed through the catheter. A recent retrospective series of 98 patients by Turk et al[53] reported revascularization (TICI ≥ 2b) in 78% of cases following direct aspiration. When stentrievers were used following failed direct aspiration, this rate rose to 95%, a previously unparalleled result.

Due to the promising results from early pilot trials of endovascular mechanical thrombectomy for AIS[55,56], randomized controlled trials were undertaken to evaluate the benefit of endovascular therapy compared to IVT in a more rigorous fashion.

Endovascular mechanical thrombectomy involves the physical extraction of an occluding thromboembolus via grasping devices and/or direct/indirect aspiration. Over the past decade, advancements in catheter-based and endovascular device technology have led to strong improvements in rates of vessel recanalization. Initial randomized trials failed to show benefit of endovascular therapy over IVT, but limitations in study design have abated widespread acceptance of their conclusions. Future randomized trials evaluating endovascular mechanical thrombectomy for AIS will need to enroll and treat patients based off of the currently accepted standards of care.