Mechanical thrombectomy for acute ischemic stroke

INTRODUCTION — Timely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver for salvaging ischemic brain tissue that is not already infarcted. There is a narrow window during which this can be accomplished since the benefit of reperfusion decreases over time.

This topic will review the use of mechanical thrombectomy (MT) for acute ischemic stroke. The approach to reperfusion therapy for acute ischemic stroke, including the use of intravenous thrombolytic therapy (recombinant tissue plasminogen activator or tPA), is reviewed elsewhere. (See "Approach to reperfusion therapy for acute ischemic stroke" and "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use".)

OVERVIEW OF REPERFUSION THERAPY — For eligible patients with acute ischemic stroke, intravenous thrombolytic therapy with alteplase or tenecteplase is first-line therapy, provided that treatment is initiated within 4.5 hours since the time the patient was last known to be well (table 1). Because the benefit is time dependent, it is critical to treat patients as quickly as possible; eligible patients should receive intravenous thrombolytic therapy without delay even if mechanical thrombectomy (MT) is being considered. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use".)

MT is indicated for patients with acute ischemic stroke due to a large artery occlusion in the anterior circulation who can be treated within 24 hours of the time last known to be well (ie, at neurologic baseline), regardless of whether they receive intravenous thrombolytic therapy for the same ischemic stroke event, as discussed in the sections that follow. Although the benefits are uncertain, MT within 24 hours of the time last known to be well may be a reasonable treatment option for patients with acute ischemic stroke caused by occlusion of the basilar artery.

Two issues may limit the widespread clinical use of MT. First, only an estimated 10 percent of patients with acute ischemic stroke have a proximal large artery occlusion in the anterior circulation and present early enough to qualify for MT within 6 hours [1-4], while approximately 9 percent of patients presenting in the 6- to 24-hour time window may qualify for MT [5]. Second, only a few stroke centers have sufficient resources and expertise to deliver this therapy [6]. However, eligible patients should receive standard treatment with intravenous thrombolysis if they present to hospitals where thrombectomy is not an option, and those with qualifying anterior circulation strokes from large artery occlusion should then be transferred, if at all possible, to tertiary stroke centers in which intra-arterial thrombectomy is available, a strategy called "drip and ship" [7].

PATIENT SELECTION — Patients with ischemic stroke caused by a proximal large artery occlusion in the anterior circulation are candidates for intra-arterial mechanical thrombectomy (MT) if they present to, or can be transferred expeditiously to, a certified stroke center with expertise in the use of endovascular techniques for acute ischemic stroke. Intra-arterial MT can be used in addition to treatment with intravenous thrombolysis using alteplase or tenecteplase. MT treatment should be started as quickly as possible and should not be delayed to assess the response to intravenous tissue plasminogen activator (tPA).

Treatment with intravenous thrombolysis prior to MT is also known as bridging therapy. The potential efficacy of bridging therapy compared with MT alone is reviewed separately. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'IVT followed by MT'.)

Who to treat — For patients with acute ischemic stroke, we recommend treatment with intra-arterial MT, whether or not the patient received treatment with intravenous thrombolytic therapy, if the following conditions are met (algorithm 1):

●Brain imaging using computed tomography (CT) without contrast or diffusion-weighted magnetic resonance imaging (DWI) excludes hemorrhage and is consistent with an Alberta Stroke Program Early CT Score (ASPECTS) ≥3. (See 'Role of ASPECTS method' below.)

●CT angiography (CTA) or MR angiography (MRA) demonstrates a proximal large vessel occlusion (including the intracranial internal carotid artery [ICA] or middle cerebral artery extending to the proximal M2 segment) in the anterior circulation as the cause of the ischemic stroke.

●The patient has a persistent, potentially disabling neurologic deficit; some guidelines require a National Institutes of Health Stroke Scale (NIHSS) score (table 2) of ≥6 points (calculator 1) [8].

●Thrombectomy can be started within 24 hours of the time the patient was last known to be well.

This recommendation applies when thrombectomy is performed at a stroke center with appropriate expertise in the use of endovascular therapy. Benefit may be most likely for patients who start treatment within 6 hours, or when imaging confirms the presence of salvageable brain tissue (eg, a mismatch by DAWN or DEFUSE 3 criteria) for patients who start treatment in the 6- to 24-hour time window. (See 'Benefit with a clinical or tissue mismatch defined by imaging' below.)

Additional considerations

●Selection with CTP or DWI/PWI using automated infarct core analysis – Patients with acute stroke due to large vessel occlusion can be selected for MT by determining if they have salvageable brain tissue, defined by a mismatch between a relatively larger area of ischemia (ie, hypoperfused brain tissue) and a smaller area of infarct core (ie, irreversibly injured brain tissue). Stroke centers with advanced imaging capability can identify mismatch using CT perfusion (CTP) imaging or DWI with perfusion-weighted magnetic resonance imaging (PWI) combined with automated software imaging analysis to determine infarct volume. The DAWN and DEFUSE 3 trials selected patients for treatment beyond 6 hours using these methods. Patients with little or no salvageable brain tissue were excluded from MT in these trials. (See 'Benefit with a clinical or tissue mismatch defined by imaging' below and "Neuroimaging of acute stroke", section on 'Mismatch and salvageable brain tissue'.)

However, with increasing experience and evidence from clinical trials, the need for CTP or DWI/PWI to select patients for MT in the late time window (6 to 24 hours) is no longer considered essential [9].

●Selection without automated infarct core analysis – At stroke centers without CTP or automated infarct volume determination, patients with acute anterior circulation ischemic stroke due to large vessel occlusion can be selected for MT by several evidence-based methods:

•The presence of a large ischemic core (eg, defined by an ASPECTS 3 to 5 or a core volume ≥50 mL) (see 'Role of ASPECTS method' below and 'Benefit for large core infarcts' below)

•Preserved collateral flow by CTA in the ischemic territory (see 'Benefit with collateral flow' below and "Neuroimaging of acute stroke", section on 'Collateral blood flow')

●Comorbidities – Patients with severe comorbidities prior to stroke onset (eg, pre-existing severe disability, life expectancy less than six months) are unlikely to benefit from MT, particularly if they have a large core infarct. However, findings from an observational study suggest that patients with slight or moderate prestroke disability, defined by a modified Rankin Scale (mRS) score (table 3) of 2 or 3, have a similar likelihood of recovery to their prestroke level of function after treatment with MT compared with patients who are independent at baseline [10].

●Prior intravenous thrombolysis – Many patients who are eligible for MT will be treated with intravenous thrombolytic therapy using alteplase or tenecteplase prior to MT. Patients who are not candidates for intravenous thrombolytic therapy can still be treated with MT if otherwise eligible according to the criteria outlined here and above (see 'Who to treat' above). As an example, patients with infective endocarditis, which is a contraindication to intravenous thrombolysis, may still undergo MT if otherwise eligible [11].

Who not to treat — While eligibility for MT has expanded since 2015 with trials showing benefit of MT in the 6- to 24-hour time window using several different selection criteria (see 'Benefit of later (6 to 24 hours) treatment' below), there are still scenarios where treatment may be futile if not dangerous. We would not treat patients with MT who have any of the following clinical and imaging findings (algorithm 1):

●Presence of a large established hypodensity on head CT beyond the more subtle, early ischemic changes assessed by ASPECTS. (See 'Role of ASPECTS method' below.)

●No ischemic penumbra (ie, no mismatch suggesting no salvageable brain tissue) on CTP or DWI/PWI if these studies are performed, particularly if the infarct core is large. However, doing CTP or magnetic resonance imaging (MRI) before MT is not essential, even in patients with low ASPECTS on CT.

●Presence of a large core infarct (eg, defined by an ASPECTS 3 to 5 or imaging showing a core volume ≥50 mL) and severe prestroke comorbidities (eg, pre-existing severe disability such as mRS 4 to 5, or life expectancy less than six months).

Individualized decisions — The decision to employ MT needs to be carefully individualized for patients with anterior circulation stroke who do not precisely match all the inclusion or exclusion criteria as listed above. Examples include patients with imaging evidence of salvageable brain tissue who are beyond the 24-hour time window [12,13], with medium vessel occlusion (eg, anterior cerebral artery, middle cerebral artery beyond the proximal M2 segment, and posterior cerebral artery) [14,15], or with minor stroke (NIHSS ≤5) [16,17]. The less severe the stroke deficits, the more difficult the treatment decision becomes because there is more to lose in case of a symptomatic hemorrhage.

Role of ASPECTS method — The ASPECTS was developed to provide a simple and reliable method of assessing ischemic changes on head CT scan in order to identify acute stroke patients unlikely to make an independent recovery despite thrombolytic treatment [18]. The ASPECTS method has also been adopted to assess the extent of ischemia on DWI; the ability to detect early ischemic changes by ASPECTS was similar on noncontrast CT and DWI [19].

Original (MCA territory) ASPECTS — The ASPECTS value is calculated from two standard axial CT cuts; one at the level of the thalamus and basal ganglia, and one just rostral to the basal ganglia (figure 1) [18,20].

●The ASPECTS method divides the middle cerebral artery (MCA) territory into 10 regions of interest.

●Subcortical structures are allotted three points: one each for caudate, lentiform nucleus, and internal capsule.

●MCA cortex is allotted seven points:

•Four of these points come from the axial CT cut at the level of the basal ganglia, with one point for insular cortex and one point each for M1, M2, and M3 regions (anterior, lateral, and posterior MCA cortex).

•Three points come from the CT cut just rostral to the basal ganglia, with one point each for M4, M5, and M6 regions (anterior, lateral, and posterior MCA cortex).

One point is subtracted for an area of early ischemic change, such as focal swelling or parenchymal hypoattenuation, for each of the defined regions.

Therefore, a normal CT scan without ischemic change has an ASPECTS value of 10 points, while diffuse ischemic change throughout the MCA territory gives a value of 0.

Posterior circulation ASPECTS — The pc-ASPECTS subtracts one point for each ischemic lesion (right or left) of the thalamus, cerebellar hemisphere, or posterior cerebral artery territory, and two points for each lesion in the mesencephalon or pons [21,22]. A normal pc-ASPECTS has a value of 10 points; lower scores indicate greater extent of infarction.

EFFICACY OF MECHANICAL THROMBECTOMY — Early (within 24 hours) intra-arterial treatment with second-generation mechanical thrombectomy (MT) devices is safe and effective for reducing disability and is superior to standard treatment with intravenous thrombolysis alone for the treatment of acute ischemic stroke caused by a documented large artery occlusion in the proximal anterior circulation (figure 2 and figure 3).

Anterior circulation stroke

Benefit of early (within 6 hours) treatment

●Landmark trials demonstrating benefit – Five multicenter, open-label randomized controlled trials (MR CLEAN [23,24], ESCAPE [25], SWIFT PRIME [26], EXTEND-IA [27], and REVASCAT [28]) demonstrated that early intra-arterial treatment with second-generation MT devices is safe and effective for reducing disability and is superior to standard treatment with intravenous thrombolysis alone for ischemic stroke caused by a documented large artery occlusion in the proximal anterior circulation [1,29-35]. The number needed to treat (NNT) for one additional person to achieve functional independence in these trials ranged from approximately 3 to 7.5 [23-28,36].

When the positive results of the MR CLEAN trial were announced in late 2014 [23], the remaining trials (ESCAPE [25], SWIFT PRIME [26], EXTEND-IA [27], and REVASCAT [28]) were stopped early on the basis of positive interim efficacy analyses. All these trials enrolled overlapping but not identical patient populations and had generally similar results.

These trials included patients with a proximal large artery occlusion in the anterior circulation as the cause of the ischemic stroke who could start treatment (femoral puncture) within 6 hours of symptom onset. They excluded patients with large core infarcts, restricting eligibility to patients with an Alberta Stroke Program Early CT Score (ASPECTS) ≥6 or an infarct core volume <50 mL as determined by CT perfusion (CTP) or diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI). However, subsequent randomized trials have shown that MT also leads to better functional outcomes for patients with a large ischemic core. (See 'Benefit for large core infarcts' below.)

●HERMES meta-analysis – In the HERMES meta-analysis of these trials, with pooled patient-level data for 1287 subjects, the rate of functional independence (ie, a 90-day modified Rankin Scale [mRS] score of 0 to 2) was significantly greater for the intervention group compared with the control group (46 versus 27 percent, odds ratio [OR] 2.35, 95% CI 1.85-2.98) [29]. Similarly, MT led to significantly reduced disability as indicated by an improvement of ≥1 point on the mRS at 90 days (adjusted OR 2.49, 95% CI 1.76-3.53). MT was beneficial across a wide range of patient subgroups, including age ≥80 years, high initial stroke severity, and those not treated with intravenous thrombolytic therapy. There was no significant difference between the MT and control groups for rates of symptomatic intracranial hemorrhage or 90-day mortality.

●Other trials demonstrating benefit – Several additional trials (THERAPY [37], PISTE [38], EASI [39], and RESILIENT [40]) also had point estimates suggesting improved functional outcomes for patients treated with MT. The RESILIENT trial, conducted in 12 public hospitals in Brazil, showed that MT can be efficacious in a country with limited health care resources [40].

●Earlier trials failed to show benefit – Earlier trials (SYNTHESIS Expansion [41], IMS III [42], and MR RESCUE [43]) failed to show benefit for intra-arterial treatment of acute ischemic stroke, in part because they used older-generation thrombectomy devices, which were less likely to achieve reperfusion (see 'Devices' below), and because they did not require routine vessel imaging to confirm a large artery occlusion as the cause of the stroke [44].

Benefit of later (6 to 24 hours) treatment — MT is also effective when used from 6 to 24 hours for patients selected by several different strategies. These strategies include imaging that confirms either the presence of salvageable brain tissue (eg, a tissue mismatch as defined by DAWN or DEFUSE 3 criteria), or demonstrates a large core infarct, or demonstrates collateral flow (by CTA [CT angiography]) ipsilateral to the ischemic hemisphere.

Thus, selection of patients for MT in the late time window (6 to 24 hours) may be done using noncontrast CT alone as an alternative to advanced imaging with CTP or DWI/PWI [45-47].

Benefit with a clinical or tissue mismatch defined by imaging — MT improves outcomes for patients with acute ischemic stroke due to occlusion of the intracranial carotid or proximal middle cerebral artery (MCA) who fulfill either the DAWN trial criteria for a clinical mismatch profile or the DEFUSE 3 trial criteria for a target perfusion mismatch profile [48].

●DAWN trial – The open-label DAWN trial enrolled 206 adults with acute ischemic stroke who were last known to be well 6 to 24 hours earlier; all had a stroke caused by occlusion of the intracranial internal carotid artery (ICA) or the proximal MCA and had a clinical mismatch between the severity of the neurologic deficit, as measured by the National Institutes of Health Stroke Scale (NIHSS; median score 17 at baseline), and the infarct volume, as measured by automated software analysis using DWI/PWI or CTP (median approximately 8 mL) [49]. Approximately 55 percent of the patients in the trial had a "wake-up" stroke (ie, they were last known to be well before going to bed and stroke symptoms were first noted upon awakening). Patients were randomly assigned to thrombectomy plus standard care or to standard care alone (control). The trial was stopped early for efficacy at the first interim analysis. The following observations were noted:

•At 90 days, the rate of functional independence, as defined by a score of 0 to 2 on the mRS, was greater for the thrombectomy group compared with the control group (49 versus 13 percent, adjusted difference 33 percent, 95% CI 24-44). The NNT for one additional patient to achieve functional independence was 3. All other efficacy outcome measures also favored thrombectomy.

•There was no significant difference between the thrombectomy and control groups in the rate of symptomatic intracranial hemorrhage (6 and 3 percent) or mortality (19 and 18 percent).

Eligibility criteria for the DAWN trial were as follows [49]:

•Treatment could be started (femoral puncture) within 6 to 24 hours of time last known to be well

•Failed or contraindicated for intravenous thrombolytic therapy with alteplase or tenecteplase

•A deficit on the NIHSS (table 2) of ≥10 points (calculator 1)

•No significant prestroke disability: baseline mRS score ≤1

•Baseline infarct involving less than one-third of the territory of the MCA on CT or MRI

•Intracranial arterial occlusion of the ICA or the M1 segment of the MCA

•A clinical-core mismatch according to age:

-Age ≥80 years: NIHSS ≥10 and an infarct volume <21 mL

-Age <80 years: NIHSS 10 to 19 and an infarct volume <31 mL

-Age <80 years: NIHSS ≥20 and an infarct volume <51 mL

●DEFUSE 3 trial – The open-label DEFUSE 3 trial enrolled patients with ischemic stroke due to occlusion of the proximal MCA or ICA who were last known to be well 6 to 16 hours earlier [50]. Patients were required to have a target perfusion mismatch characterized by an infarct size of <70 mL and a ratio of ischemic tissue volume to infarct volume of ≥1.8, as measured by automated software processing of DWI/PWI or CTP imaging. The DEFUSE 3 trial was stopped early for efficacy after randomly assigning 182 patients to thrombectomy plus standard care or to standard care alone. Approximately one-half of the patients in the trial had a "wake-up" stroke. Patients assigned to thrombectomy were treated with stent retrievers or aspiration catheters. At 90 days, the percentage of patients who were functionally independent, defined as an mRS score of 0 to 2, was higher with endovascular therapy compared with medical therapy alone (45 versus 17 percent, difference 28 percent), and therefore the NNT for one additional patient to achieve functional independence was 3.6. There was also a trend to lower mortality with endovascular therapy (14 versus 26 percent). There was no significant difference between groups in the rate of symptomatic intracranial hemorrhage (7 and 4 percent) or serious adverse events (43 and 53 percent).

Eligibility criteria for DEFUSE 3 were as follows [50]:

•Treatment could be started (femoral puncture) within 6 to 24 hours of time last known to be well

•A deficit on the NIHSS (table 2) of ≥6 points (calculator 1)

•Only slight or no prestroke disability: baseline mRS score ≤2

•Arterial occlusion of the cervical or intracranial ICA (with or without tandem MCA lesions) or the M1 segment of the MCA demonstrated on MR angiography (MRA) or CTA

•A target mismatch profile on CTP or DWI/PWI defined as an ischemic core volume <70 mL, a mismatch ratio (the volume of the perfusion lesion divided by the volume of the ischemic core) >1.8, and a mismatch volume (volume of perfusion lesion minus the volume of the ischemic core) >15 mL

•Age 18 to 90 years

●AURORA study – The AURORA study analyzed pooled patient-level data from 505 individuals from six randomized controlled trials of MT, including DAWN and DEFUSE 3, that included patients enrolled beyond 6 hours after they were last known to be well and who received treatment with a second-generation stent retriever [51]. At 90 days, MT led to higher rates of independence in activities of daily living, defined by an mRS of 0 to 2, compared with best medical therapy alone (45.9 versus 19.3 percent, adjusted relative risk [RR] 2.19, 95% CI 1.44-3.34, absolute risk reduction 26.6 percent). The NNT for one additional person to achieve functional independence in AURORA was approximately 4. The MT and best medical treatment groups had similar rates of mortality (16.5 versus 19.3 percent) and symptomatic intracerebral hemorrhage (5.3 versus 3.3 percent).

The AURORA investigators also compared outcomes among three subgroups: first, patients (n = 295) who met criteria for a clinical mismatch profile as used in the DAWN trial; second, patients (n = 359) who met criteria for a target perfusion mismatch profile as used in the DEFUSE 3 trial; and third, patients (n = 132) with an undetermined mismatch profile due to the absence of an adequate CT or MRI perfusion study [52]. At 90 days, MT led to reduced disability for both the clinical mismatch subgroup (OR 3.57, 95% CI 2.29-5.57) and the target perfusion mismatch subgroup (OR 3.13, 95% CI 2.10-4.66). Importantly, the benefit was significant in both subgroups for the entire 6- to 24-hour time window. There was a trend toward benefit for patients with an undetermined profile that did not reach statistical significance (OR 1.59, 95% CI 0.82-3.06).

Limitations to these trials include stopping early, which can overestimate treatment effects. However, this drawback is at least partially offset by the relatively large effect size demonstrated in the trials and meta-analysis [49-51].

Although not definitive, evidence from a retrospective study of patients with anterior circulation large vessel occlusion presenting in the 6- to 24-hour time window who did not meet DAWN or DEFUSE 3 inclusion criteria found that treatment with MT (n = 102), performed at the discretion of the treating neurointerventionalist, was associated with higher odds of an improved functional outcome at three months compared with medical treatment alone (n = 88) as measured by a shift in the mRS score (adjusted common OR 1.46, 95% CI 1.02-2.10) [53].

Benefit for large core infarcts — MT improves outcomes for patients with acute anterior circulation ischemic stroke due to large vessel occlusion who have a large ischemic core (eg, defined by an ASPECTS 3 to 5 or by a core volume ≥50 mL), as shown by randomized controlled trials including RESCUE-Japan LIMIT [54], SELECT2 [55], and ANGEL-ASPECT [56]. Despite differences in design, patient ethnicity, geographic location, and imaging criteria, all three trials showed benefit of thrombectomy for patients with large ischemic strokes treated within 24 hours from the time they were last known to be well [57].

Positive results from the RESCUE-Japan LIMIT trial prompted interim analyses that determined efficacy of the SELECT2 and ANGEL-ASPECT trials [54-56]. Both trials were then stopped early, which can result in overestimation of treatment effects. However, this concern is partially mitigated by the consistent benefit of thrombectomy shown in all three trials. In a 2023 meta-analysis of these three trials, functional independence (ie, an mRS score of 0 to 2) was more likely with thrombectomy compared with medical management alone (23.5 versus 9.0 percent, RR 2.59, 95% CI 1.89-3.57) [58]. The NNT for one additional person to achieve functional independence (ie, an mRS score of 0 to 2) was approximately 7.

Note that all three trials enrolled patients who had very severe stroke deficits at baseline and enrolled very few octogenarians or excluded them entirely. Despite the benefit of MT, most of these patients were left with substantial disability; in the MT arms in SELECT2 and ANGEL-ASPECT at 90 days, the median mRS score was 4. Nevertheless, MT should now be considered the standard for patients with very disabling deficits, even if they have large ischemic core.

●RESCUE-Japan LIMIT trial – The earlier requirement for a small infarct core as a criterion for MT eligibility was first challenged in 2022 by results from the RESCUE-Japan LIMIT trial, which enrolled 203 patients (18 years of age or older) with acute ischemic stroke due to a proximal MCA or ICA occlusion and a low ASPECTS of 3 to 5 on CT or DWI, consistent with a large infarct core (see 'Role of ASPECTS method' above) [54]. Patients were randomly assigned in a 1:1 ratio to endovascular therapy with medical care or medical care alone; enrolled patients were within 6 hours after the time last known to be well (n = 145) or within 6 to 24 hours after the time last known to be well if fluid-attenuated inversion recovery (FLAIR) MRI showed no signal change (n = 58), suggesting very recent infarction.

At 90 days, more patients had a "good" outcome, defined by an mRS score of 0 to 3, in the endovascular therapy group compared with the medical care group (31.0 versus 12.7 percent, RR 2.43, 95% CI 1.35-4.37) [54]. For the outcome of an mRS of 0 to 2 (ie, functional independence), there was a trend towards benefit with endovascular therapy (14 versus 7.8 percent, RR 1.79, 95% CI 0.78-4.07). The endovascular group had a nonsignificantly higher rate of symptomatic intracranial hemorrhage (9 versus 4.9 percent, RR 1.84, 95% CI 0.64-5.29) and a higher rate of any intracranial hemorrhage (58 versus 31.4 percent, RR 1.84, 95% CI 1.33-2.58).

Limitations of this trial include concerns about generalizability beyond the Japanese population, and relatively small patient numbers in the 6- to 24-hour treatment subgroup [54].

●SELECT2 trial – This trial enrolled adult patients 18 to 85 years of age with a large ischemic core, defined by an ASPECTS of 3 to 5 or a core volume of ≥50 mL [55]. There were 31 participating sites across the United States, Canada, Europe, Australia, and New Zealand. Patients were randomly assigned to thrombectomy plus medical care (n = 178) or medical care only (n = 174) within 24 hours of the time last known to be well. The median age was 66.5 years, the median NIHSS was 19, and the median time to randomization was 9.3 hours. The trial was stopped early for efficacy. At 90 days, there was a shift in the distribution of the mRS scores toward better outcomes for the thrombectomy group (OR 1.51, 95% CI 1.20-1.89). Functional independence (ie, an mRS score of 0 to 2) was also more likely with thrombectomy (20 percent, versus 7 percent with medical care, RR 2.97, 95% CI 1.60-5.51). Mortality was similar for the thrombectomy and medical care groups (38.4 versus 41.5 percent). Symptomatic intracranial hemorrhage occurred in only one patient in the thrombectomy group and two in the medical care group. Early neurologic worsening was more frequent with thrombectomy (24.7 versus 15.5 percent) and was associated with larger baseline infarct size and worse outcomes. Procedural complications, including dissection and cerebral vessel perforation, affected approximately 20 percent of patients in the thrombectomy group.

●ANGEL-ASPECT trial – This trial enrolled patients 18 to 80 years of age with a large ischemic core, defined by an ASPECTS of 3 to 5 or an infarct core volume of 70 to 100 mL [56]. The trial was conducted at 46 stroke centers in China. Patients were randomly assigned to thrombectomy plus medical management (n = 231) or medical management alone (n = 225). The median age was 68 years, the median NIHSS was 16, and the median time to randomization was 7.6 hours. The trial was stopped early for efficacy. At 90 days, there was a shift in the distribution of the mRS scores toward better outcomes for the thrombectomy group (OR 1.37, 95% CI 1.11-1.69). Functional independence (ie, an mRS score of 0 to 2) was more likely for the thrombectomy group compared with the medical treatment group (30.0 versus 11.6 percent, OR 2.62, 95% CI 1.69-4.06). Mortality was similar for the thrombectomy and medical care groups (21.7 versus 20 percent). The thrombectomy group had a higher numerical rate of symptomatic intracranial hemorrhage (6.1 versus 2.7 percent, OR 2.07, 95% CI 0.79-5.41), but the difference was not statistically significant.

Benefit with collateral flow — MT improves outcomes for patients who have preserved collateral flow by CTA in the ischemic territory, as shown by the MR CLEAN-LATE trial [59]. The trial enrolled 535 adults presenting in the 6- to 24-hour time window with an acute anterior circulation stroke due to large vessel occlusion who had some degree of collateral flow in the MCA territory of the affected hemisphere by single-phase CTA or the arterial phase of multiphase CTA; patients eligible for MT by DAWN or DEFUSE 3 trials were excluded. Enrolled patients were randomly assigned in a 1:1 ratio to MT or no MT (control). The median age was 74 years, the median NIHSS score was 10, the median ASPECTS was 9 and 8 in the treatment and control groups, respectively, and the median time to randomization was approximately 11.5 hours. At 90 days, functional independence (an mRS score of 0 to 2) was achieved by more patients in the thrombectomy group compared with the control group (39 versus 34 percent), but the difference just missed statistical significance (OR 1.54, 95% CI 0.98-2.43). The thrombectomy group had improved outcomes compared with the control group by the median mRS (3 versus 4) and a shift in the distribution of the mRS scores favoring thrombectomy (OR 1.67, 95% CI 1.20-2.32). Mortality was lower in the thrombectomy group, but the difference was not statistically significant (24 versus 30 percent, OR 0.72, 95% CI 0.44-1.18), while symptomatic intracranial hemorrhage was more frequent in the thrombectomy group (7 versus 4 percent, OR 4.59, 95% CI 1.49-14.10).

Earlier studies also suggested that moderate to good collateral flow status on CTA is useful for identifying patients who are likely to benefit from MT [8,25,60,61].

Posterior circulation stroke — MT within 24 hours of the time last known to be well may be a reasonable treatment option for patients with acute ischemic stroke caused by occlusion of the basilar artery, when performed at centers with appropriate expertise. The value of MT for occlusions of the vertebral arteries and posterior cerebral arteries is uncertain [8,62-68].

Basilar artery occlusion — There is moderate-quality evidence that MT is beneficial for patients of Chinese ancestry who can be treated within 24 hours of moderate to severe stroke (an NIHSS score ≥10) caused by a basilar artery occlusion if the posterior circulation ASPECTS (pc-ASPECTS) score is consistent with a limited extent of ischemia [69,70]. (See 'Posterior circulation ASPECTS' above.)

●ATTENTION trial – The ATTENTION trial evaluated patients from China with moderate to severe stroke (with an NIHSS ≥10) due to basilar artery occlusion who were within 12 hours of the estimated time of stroke onset and had a limited degree of early ischemic change, as quantified by the pc-ASPECTS [69]. Patients were randomly assigned in a 2:1 ratio to medical care plus endovascular thrombectomy or medical care alone (control). At baseline, the median NIHSS score was 24 in each group. Approximately one-third of patients in each group received intravenous thrombolysis. At 90 days, the rate of good functional status (ie, an mRS score of 0 to 3) was higher in the thrombectomy group compared with the control group (46 versus 23 percent, adjusted RR 2.06, 95% CI 1.46-2.91) and the mortality rate was lower in the thrombectomy group (37 versus 55 percent, RR 0.66, 95% CI 0.52-0.82). The rate of functional independence (ie, an mRS score of 0 to 2) was also higher in the thrombectomy group (33 versus 11 percent, RR 3.17, 95% CI 1.84-5.46), and results for most secondary outcomes favored thrombectomy. Symptomatic intracranial hemorrhage occurred in 5 percent of cases in the thrombectomy group versus none in the control group. MT was associated with procedural complications in 14 percent of patients, including one death caused by arterial perforation.

●BAOCHE trial – The BAOCHE trial from China evaluated patients within 6 to 24 hours after stroke onset due to basilar artery occlusion [70]. Patients were randomly assigned in a 1:1 ratio to MT plus medical care with medical care alone. The trial was stopped early after an interim analysis suggested superiority of thrombectomy. At baseline, the median NIHSS was 20 for the thrombectomy group and 19 for the control group. The rate of intravenous thrombolysis was 14 percent in the thrombectomy group and 21 percent in the control group. At 90 days, the rate of good functional status (ie, an mRS score of 0 to 3) was higher in the thrombectomy group compared with the control group (46 versus 24 percent, RR 1.81, 95% CI 1.26-2.60), and the rate of functional independence (ie, an mRS score of 0 to 2) was also higher in the thrombectomy group (39 versus 14 percent, RR 2.64, 95% CI 1.54-4.50). There was a trend for lower mortality at 90 days favoring the thrombectomy group (31 versus 42 percent, RR 0.75, 95% CI 0.54-1.04). Symptomatic intracranial hemorrhage occurred more often in the thrombectomy group (6 versus 1 percent, RR 5.18, 95% CI 0.64-42.18). Procedural complications occurred in 11 percent of the thrombectomy group.

The ATTENTION and BAOCHE trial results are not generalizable to all patients with basilar artery stroke. The Chinese population has higher rates of large artery intracranial atherosclerotic disease relative to other populations, and many patients in the thrombectomy groups of both trials were also treated with angioplasty and/or stenting of the basilar artery. The low rates of treatment with intravenous thrombolysis in both trials may have reduced the rates of good outcomes particularly affecting the control groups and biased the results in favor of thrombectomy.

Earlier trials were also limited by methodologic issues. A randomized trial (BEST) comparing endovascular treatment (MT) with standard medical care for patients with acute vertebrobasilar occlusion who could be treated within eight hours was stopped early for slow recruitment and high crossover rate after enrolling 131 patients [62]. Compared with standard medical care, patients assigned to endovascular therapy had similar rates of favorable outcome and 90-day mortality by intention-to-treat analysis. The BASICS trial of 300 patients with acute ischemic stroke attributed to basilar artery occlusion found no statistically significant difference in outcomes for endovascular therapy compared with medical therapy [64]. However, there was a nonsignificant trend of benefit with endovascular treatment in both trials [62,64].

Larger randomized controlled trials in more diverse populations are needed to assess the efficacy of endovascular therapy for posterior circulation stroke due to large artery occlusion.

PROCEDURE

Overview — General anesthesia or conscious sedation may be used for the procedure, depending upon local preference and experience. (See 'Anesthesia' below.)

Catheterization is commonly performed with femoral artery puncture. The catheter is guided to the internal carotid artery (ICA) and beyond to the site of the intracranial large artery occlusion. The stent retriever is then inserted through the catheter to reach the clot. The stent retriever is deployed and grabs the clot, which is removed as the device is pulled back. The initial goal is to achieve reperfusion, defined by a modified Thrombolysis in Cerebral Infarction (mTICI) perfusion grade 2b (anterograde reperfusion of more than half in the downstream target arterial territory) or grade 3 (complete anterograde reperfusion of the downstream target arterial territory) (table 4), as early as possible [8,71]. In a meta-analysis of five trials that evaluated treatment within 6 hours of symptom onset, over 500 patients received mechanical thrombectomy (MT), and substantial reperfusion (mTICI score of 2b or 3) was achieved in 71 percent of this group [35].

Following the procedure, most centers monitor patients in an intensive care unit setting until stable.

Devices — Both second-generation stent retrievers and catheter aspiration devices can be used for MT. The choice between them depends mainly upon local expertise and availability [72]. In some cases, treatment using stent retrievers and aspiration techniques in combination may be appropriate.

●Stent retrievers – Several MT devices are approved in the United States and Europe for clot removal in patients with acute ischemic stroke due to large artery occlusion. These include the first-generation Merci Retriever and Penumbra System devices, the second-generation Solitaire Flow Restoration Device and Trevo Retriever, and the third-generation Tigertriever. The first-generation Merci and Penumbra devices may increase recanalization rates in carefully selected patients, but their clinical utility for improving outcomes after stroke is unproven [73-75]. When compared directly with the Merci retriever in small randomized trials, the second-generation Solitaire and Trevo neurothrombectomy devices achieved significantly higher reperfusion rates and better patient outcomes [76,77]. In a single-arm study, the Tigertriever device achieved higher reperfusion rates, improved patient outcomes, and had similar safety outcomes compared with historical controls from studies of the Solitaire and Trevo devices [78].

In light of these data and the positive thrombectomy trials discussed above [23,25-28], which preferentially used the second-generation devices, only the second-generation or later devices should be used to treat patients with acute ischemic stroke.

●Catheter aspiration devices – Catheter aspiration devices are another option for MT. This method employs a catheter to aspirate the thrombus as the first approach to performing thrombectomy; if aspiration alone does not achieve reperfusion after one or more passes, a stent retriever can be inserted through the catheter to complete the thrombectomy.

Mounting evidence suggests that catheter aspiration devices can attain rates of revascularization [37,79] and good functional outcome [80,81] that are similar to the rates achieved with second-generation stent retrievers. The open-label, multicenter COMPASS trial randomly assigned 270 patients within 6 hours of symptom onset to MT with either catheter aspiration as first-pass treatment or stent retriever first-line [80]. At 90 days, a good functional outcome (modified Rankin Scale [mRS] score of 0 to 2) was achieved by a similar number of patients in each treatment group (52 versus 50 percent for aspiration first-pass and stent retriever first-line, respectively), indicating that aspiration first-pass was noninferior to stent retriever first-line treatment. In addition, secondary efficacy and angiographic outcome measures did not differ between treatment groups, and there were no significant differences in mortality, symptomatic intracranial hemorrhage, or other safety outcomes.

One trial found a trend to higher rates of near-total or total reperfusion for combined stent retriever plus aspiration compared with stent retriever alone, but the difference did not achieve statistical significance (64.5 versus 57.9 percent, risk difference 6.6 percent, 95% CI -3.0 to 16.2) [82].

Anesthesia — Either monitored anesthesia care (also called conscious sedation) or general anesthesia may be used for procedural sedation during MT. The anesthetic technique should be chosen based upon individual patient risk factors, preferences, and institutional experience [8]. (See "Anesthesia for endovascular therapy for acute ischemic stroke in adults", section on 'Choice of anesthetic technique: General anesthesia versus monitored anesthesia care'.)

The type of anesthesia used for MT in patients with ischemic stroke may have some impact on short- and long-term outcomes, as reviewed in detail separately. (See "Anesthesia for endovascular therapy for acute ischemic stroke in adults", section on 'Literature comparing general anesthesia with monitored anesthesia care or conscious sedation'.)

Risk of periprocedural antithrombotics — There is no indication for the routine use of periprocedural antithrombotic agents. Based upon the results of the MR CLEAN-MED trial, the use of periprocedural aspirin or unfractionated heparin in patients undergoing endovascular therapy for acute ischemic stroke increases the risk of symptomatic hemorrhagic transformation and may increase the risk of worse outcomes [83]. However, antithrombotic agents may be indicated in specific instances (eg, if a stent gets deployed, or if there is distal embolism).

Blood pressure

●Admission blood pressure – Admission systolic blood pressure (SBP) does not seem to impact the benefit of MT, as shown by the HERMES meta-analysis of seven trials with individual data from 1753 patients randomly assigned to MT or standard care (control) [84]. The meta-analysis found a nonlinear association between admission SBP and functional outcome measured by the mRS, with an inflection point at an SBP of 140 mmHg. Admission SBPs above 140 mmHg were associated with worse functional outcomes and higher mortality rates. However, there was no interaction between admission SBP and the effect of MT. At 90 days, the median mRS was lower (ie, functional outcome was better) with MT for both patients with an admission SBP <140 mmHg (median mRS 2, versus 3 for controls) and patients with an admission SBP ≥140 mmHg (median mRS 3, versus 4 for controls). The benefit of MT for a shift towards a better functional outcome ordinal mRS was also similar for patients with admission SBP <140 mmHg (adjusted common OR 2.06, 95% CI 1.56-2.71) and patients with admission SBP ≥140 mmHg (OR 1.84, 95% CI 1.46-2.31).

●Management prior to reperfusion – We suggest keeping SBP between 150 and 180 mmHg prior to reperfusion; SBP ≥150 mmHg may be useful for maintaining adequate collateral blood flow during the time the large artery remains occluded [8,25]. Some experts suggest no use of antihypertensives prior to reperfusion unless SBP exceeds 200 mmHg for patients not being treated with intravenous thrombolysis, or unless SBP exceeds 185 mmHg for patients who are candidates for intravenous thrombolysis [85].

Many patients undergoing MT will have been treated with intravenous thrombolytic therapy (recombinant tissue plasminogen activator or tPA) in the first hours after stroke symptom onset and should be managed accordingly, with systolic/diastolic blood pressure maintained at ≤180/105 mmHg during and for 24 hours following alteplase infusion or tenecteplase injection; a higher blood pressure may increase the risk of hemorrhage in ischemic brain regions even when thrombolytic agents are not used. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use", section on 'Management of blood pressure'.)

●Management after reperfusion – We suggest allowing blood pressure to autoregulate for most patients after successful reperfusion therapy, reserving blood pressure intervention for cases with severe hypertension (SBP >180 mmHg) or hypotension [86]. The optimal blood pressure range with MT is not well defined; there is no proven benefit – and possible harm – with aggressive early blood pressure reduction after reperfusion [87-90]. Earlier evidence supported keeping SBP <160 to 170 mmHg for patients with successful reperfusion (ie, mTICI 2b or 3) and targeting SBP of 170 mmHg for patients with less successful reperfusion (ie, mTICI 0 to 2a) [85]. More intensive blood pressure lowering (eg, targeting SBP <140 mmHg) may be harmful, particularly in Asian populations where the prevalence of large artery atherosclerosis is high [90-92].

Adverse effects — In the MR CLEAN trial, clinical signs of a new ischemic stroke in a different vascular territory within 90 days of treatment were more common in the intra-arterial group compared with no endovascular therapy (5.6 versus 0.4 percent) [23]. Device-related serious adverse events are uncommon but include access site hematoma and pseudoaneurysm, arterial perforation, and arterial dissection [25-28]. Transient intraprocedural vasospasm is also uncommon but is sometimes treated.

MT in general is not associated with increased rates of symptomatic intracranial hemorrhage (sICH) or mortality. In a meta-analysis of five trials, with pooled patient-level data for 1287 subjects, there was no significant difference between the intervention population and control population for 90-day sICH (4.4 versus 4.3 percent) or mortality (15 versus 19 percent) [29].

Limited evidence suggests recent anticoagulation with an oral vitamin K antagonist (VKA), but not a direct oral anticoagulant (DOAC), may increase the risk of sICH or mortality for patients undergoing MT [93,94]. In a 2022 meta-analysis of 15 nonrandomized studies, VKA use compared with no oral anticoagulant use was associated with an increased risk of sICH (8.4 versus 6.5 percent, OR 1.49, 95% CI 1.10-2.02) and mortality (32.8 versus 24.2 percent, OR 1.67, 95% CI 1.35-2.06), whereas DOAC use compared with no oral anticoagulant use was associated with no increased risk of sICH (2.7 versus 5.9 percent, OR 0.80, 95% CI 0.45-1.44) or mortality (26.9 versus 23.0 percent, OR 1.27, 95% CI 0.96-1.70) [93].

Approach to tandem lesions — Fifteen to 30 percent of patients eligible for MT present with tandem lesions characterized by extracranial carotid artery stenosis or occlusion and a downstream, ipsilateral intracranial large vessel occlusion [23,25,28,95]. MT is directed at revascularization of the intracranial occlusion, but the best approach to management of the extracranial carotid lesion is uncertain [95,96]. Options include acute treatment of the extracranial carotid lesion with stent placement (anterograde or retrograde), angioplasty alone, or thrombo-aspiration alone, versus deferred or no revascularization of the extracranial carotid artery lesion (figure 4) [97]. Deferred revascularization options include eventual carotid endarterectomy or carotid artery stenting. (See "Management of symptomatic carotid atherosclerotic disease".)

Available data from observational studies suggest that acute carotid stenting for patients with tandem lesions who are undergoing MT is associated with a higher rate of favorable outcomes at 90 days compared with no stenting [98,99]. A subgroup analysis from one study further suggests that stenting is associated with improved outcomes in patients with carotid lesions caused by atherosclerosis but not in patients with carotid lesions caused by dissection [99].

Rescue therapy for failed MT — Approximately 8 to 30 percent of patients fail to achieve substantial reperfusion with MT, with failure defined by mTICI scores (table 4) of 2a or less [29,100-102]. In such cases, urgent rescue therapy with intracranial angioplasty/stenting, intravenous glycoprotein IIb/IIIa inhibitors, or intravenous P2Y12 receptor inhibitors is sometimes attempted [100]. Limited observational data suggest that these interventions are safe [100,103], but prospective studies are lacking, and the optimal approach is uncertain.

Intracranial stenting is the best-studied option [104-106]. The retrospective, multicenter SAINT study of patients who failed MT compared those who received acute rescue stenting (n = 107) with propensity-score matched patients who did not receive rescue stenting (n = 107) [104]. At 90 days, rescue stenting was associated with a shift to lower rates of disability in the overall mRS score distribution (adjusted OR 3.74, 95% CI 2.16-6.57), increased functional independence (34.6 versus 6.5 percent, OR 10.91, 95% CI 4.11-28.92), decreased mortality (29.9 versus 43.0 percent, OR 0.49, 95% CI 0.25-0.94), and comparable rates of symptomatic intracranial hemorrhage (7.5 versus 11.2 percent, OR 0.87, 95% CI 0.31-2.42). These results are limited by retrospective design and wide confidence intervals, and further study is needed to determine the benefit of this intervention for failed MT.

Adjunct intra-arterial thrombolysis — Some patients have poor clinical outcomes after MT despite successful reperfusion (ie, a modified Thrombolysis in Cerebral Infarction [mTICI] 2b or 3) of the target large artery; one possible but controversial explanation is persisting impaired reperfusion of the microcirculation (the "no-reflow" phenomenon) [107,108]. The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial investigated the use of adjunct intra-arterial thrombolysis with alteplase to treat hypothesized persistent thrombi in the microcirculation after angiographically successful MT [109]. At 90 days, more patients achieved an excellent neurologic outcome (an mRS score of 0 to 1) with intra-arterial alteplase compared with placebo (59 versus 40.4 percent, adjusted absolute risk reduction 18.4 percent, 95% CI 0.3-36.4 percent). There was no increased risk of intracranial hemorrhage or mortality with intra-arterial alteplase.

Limitations of the CHOICE trial include early stopping (due to slow recruitment and inability to obtain placebo), which can lead to overestimation of treatment effects, small patient numbers (and resulting wide confidence intervals with a lower limit of only 0.3 percent absolute risk reduction), and the protocol allowing premature stopping (and therefore potential underdosing) of intravenous alteplase infusion started before the onset of thrombectomy [109,110]. Thus, the benefit of this approach requires confirmation in larger trials.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".)

SUMMARY AND RECOMMENDATIONS

●Efficacy of mechanical thrombectomy – Early intra-arterial treatment with mechanical thrombectomy (MT) is safe and effective for reducing disability and is superior to standard treatment with intravenous thrombolysis alone for ischemic stroke caused by a documented large artery occlusion in the proximal anterior circulation. (See 'Efficacy of mechanical thrombectomy' above.)

●Patient selection for anterior circulation stroke

•Who to treat – For patients with acute ischemic stroke, we recommend treatment with intra-arterial MT (algorithm 1), whether or not the patient received treatment with intravenous thrombolytic therapy, if the following conditions are met (Grade 1B):

-Brain imaging using CT without contrast or diffusion-weighted MRI (DWI) excludes hemorrhage and is consistent with an Alberta Stroke Program Early CT Score (ASPECTS) ≥3. (See 'Role of ASPECTS method' above.)

-CT angiography (CTA) or MR angiography (MRA) demonstrates a proximal large artery occlusion in the anterior circulation as the cause of the ischemic stroke.

-The patient has a persistent, potentially disabling neurologic deficit (eg, a National Institutes of Health Stroke Scale [NIHSS] score ≥6).

-The patient can start treatment (femoral puncture) within 24 hours of the time last known to be well.

This recommendation applies when thrombectomy is performed at a stroke center with appropriate expertise in the use of endovascular therapy. Benefit may be most likely when imaging confirms the presence of salvageable brain tissue (eg, a mismatch by DAWN or DEFUSE 3 criteria).

•Who not to treat – We would not treat with MT for patients who have any of the following findings (see 'Who not to treat' above):

-Presence of a large established hypodensity on head CT beyond the more subtle, early ischemic changes assessed by ASPECTS (see 'Role of ASPECTS method' above)

-No ischemic penumbra (ie, no mismatch suggesting no salvageable brain tissue) identified if CT perfusion (CTP) or DWI/PWI (perfusion-weighted MRI) is performed, particularly if the infarct core is large

-Presence of a large core infarct (eg, defined by an ASPECTS <6 or imaging showing a core volume ≥50 mL) and severe prestroke comorbidities (eg, pre-existing severe disability such as modified Rankin Scale [mRS] 4 to 5 or life expectancy less than six months)

•Individualized decisions – The decision to employ MT needs to be carefully individualized for patients with anterior circulation stroke who do not precisely match the inclusion or exclusion criteria as listed above. Examples include patients with imaging evidence of salvageable brain tissue who are beyond the 24-hour time window, medium vessel occlusion (eg, anterior cerebral artery beyond the A1 segment, middle cerebral artery [MCA] beyond the proximal M2 segment), or minor stroke (NIHSS ≤5).

●Use in posterior circulation stroke – MT within 24 hours of the time last known to be well may be a reasonable treatment option for patients with acute ischemic stroke caused by occlusion of the basilar artery, when performed at centers with appropriate expertise. The value of MT for occlusions of the vertebral arteries and posterior cerebral arteries is uncertain. Moderate-quality evidence supports the benefit of MT for patients of Chinese ancestry with basilar artery occlusion who have an NIHSS score ≥10, indicating a moderate to severe stroke; a posterior circulation ASPECTS (pc-ASPECTS) of ≥6, indicating a limited extent of ischemic change on brain imaging; and who can be treated within 24 hours of time last known to be well. (See 'Posterior circulation stroke' above.)

●Procedure – Second-generation stent retriever devices or catheter aspiration devices should be used for MT. Other aspects of the MT procedure, including anesthesia, blood pressure management, and adverse events, are discussed above. (See 'Procedure' above.)