Intro:

Mechanical thrombectomy has revolutionized stroke care for patients with large vessel occlusions (LVOs). LVOs account for ~40% of all AIS, and prior to endovascular therapy more than half of these patients suffered significant post-stroke disability (modified Rankin Scale (mRS) 4-5) or death (mRS 6).

The HERMES collaboration pooled patient-level data collected between December 2010 and December 2014 from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) and included 1287 patients (634 assigned to endovascular thrombectomy; 653 assigned to control); this meta-analysis demonstrated that endovascular thrombectomy within 6 hours from last seen well (LSW) led to significantly reduced disability at 90 days compared with controls (adjusted cOR 2·49, 95% CI 1·76–3·53; p<0·0001).

The number of patients with an LVO needed to treat with endovascular thrombectomy to reduce disability by at least one level on the modified Rankin Scale for one patient was 2·6.

This post reviews who qualifies for mechanical thrombectomy, the process of screening, and how the field of interventional neurology continues to evolve.

Sections: 

• Steps to Qualify for Mechanical Thrombectomy
  • Considerations when <6 hours from last seen well (LSW)
  • Considerations when 6-24 hours from LSW
• Ongoing Investigations
  • Low ASPECT Score
  • Posterior Circulation
  • Bridging
  • IA + mechanical thrombectomy
• Summary and Rapid Reference

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Steps to Qualify for Mechanical Thrombectomy

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Not all stroke patients qualify for Mechanical Thrombectomy (MT) which is also called endovascular therapy (EVT).

Step 1:

Is there a large vessel occlusion (LVO)?

An LVO is an occlusion in the Internal Carotid Artery (ICA) or first portion of the Middle Cerebral Artery (M1) or the Basilar Artery.

Step 2:

Baseline status matters which is commonly communicated using the modified Rankin Scale (mRS). An mRS of 0-1 was included in trials.  Discuss higher mRS baselines with the proceduralists, as they may be considered on a case-by-case basis.

Step 3:

<6 hours since LSW

• Data supports using just the Albert Stroke Program Early CT (ASPECT) Score as a screening tool for patients in the early window (PMID: 34844423).  The criteria for inclusion into thrombectomy trials was an ASPECT Score ≧6.
  • Part 1 of AIS covered how to calculate ASPECT Score; there is also a wealth of educational materials here
• Any patient with LSW within 6 hours, ASPECT Score ≧6, an anterior circulation (M1 or ICA) LVO, and reasonable functional baseline should be expedited to thrombectomy

6-24 hours since LSW

• DAWN (PMID: 29129157) and DEFUSE 3 (PMID: 29364767) trials were the landmark trials demonstrating efficacy of thrombectomy in appropriately selected patients beyond the 6 hour window
• Selection depends on imaging characteristics:
  • The trials required patients have advanced neuroimaging (either CT Perfusion or MR Perfusion). The degree of infarcted territory and territory at risk (penumbra) was characterized as the “mismatch ratio.”
  • In these trials, patients were considered for mechanical thrombectomy if the cerebral blood flow (CBF) <30% tissue (🟣purple in the image below = ischemic tissue, “core”) was <51cc (DAWN) or <70cc (DEFUSE3) and there was significant tissue at risk (🟢green = penumbra) or there was a significant clinical mismatch (see the image ⬇️).
• The numbers are less important than the gestalt here — you can be a long way out from LSW and if you still have tissue that is not infarcted and an LVO, there is potential benefit for thrombectomy.  
• Discussions about “matched” or “mismatched” refer to:
  • The green and purple perfusion images are “matched.”  This is a poor thrombectomy candidate because there is likely no tissue to salvage.
  • “Matched” may also mean the patient's stroke deficits “match” the the tissue infarcted (either by ASPECTS or perfusion); again, that's a patient that is unlikely to benefit from reperfusion.
  • “Mismatched” means there is significant tissue to save.
• In both trials, performing thrombectomy in the appropriately selected patients resulted in a very small number needed to treat (~2.8 people, DAWN) for functional independence at 90 days

A key to the Perfusion Images

Purple: Ischemic Tissue, “core” CBF<30%

Green: Penumbra (delayed transit time). This tissue is at risk for stroke, but is not yet ischemic.

Do you have to have the fancy advanced neuroimaging?

• No
• The recently published The CLEAR study demonstrated that for patients with LVO in late window, the mRS scores at 90 days were equivalent for patients selected by NCHCT (ASPECT Score, see part 1) compared with patients selected by CTP or MRI (PMID: 34747975)

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Ongoing Investigations

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What if the ASPECT Score is <6?

• Retrospective studies looking at ASPECT 2-5 have demonstrated a signal of benefit with EVT (PMID: 34878550)
• A randomized trial, RESCUE-Japan LIMIT was just presented at #ISC2022 which demonstrated that EVT could double the number of patients with an mRS of 0-3 at 90 days. There were more ICHs in the EVT group but the symptomatic ICH rate remained the same.
• This trial paves the way for expansion of EVT to patients who were previously thought to be poor candidates
• For now, ASPECT Score ≧6 remains the standard to qualify for EVT in most centers.  Lower ASPECT Scores can be discussed with the proceduralist on a case-by-case basis

Posterior Circulation

• Devastating outcomes occur in about 80% of untreated basilar occlusions (PMID: 19577962)
• Enrollment into clinical trials has been slowed by the lack of equipoise: real-world experience and registry data has demonstrated improved outcome in patients with posterior circulation occlusions (PMID: 34753304).
• Similar to anterior LVOs, patients with Basilar Occlusions can be screened with a posterior circulation ASPECT score (pc-ASPECTS).  10 is a perfect score, and points are subtracted for evidence of early ischemic changes in the posterior circulation territory.
• Recent analysis suggest that pc-ASEPCTS ≧ 5 may benefit from thrombectomy.
• Subgroup analysis and refining patient selection to those who have the most to gain are current topics of research
• For now, if a patient presents with an acute basilar artery occlusions within 24 hours since symptoms onset, it is reasonable to discuss treatment with an endovascular capable center. Advanced neuroimaging may be requested on a case-by-case basis.

Bridging

“Bridging” is the term used for giving thrombolysis to patients who are bound for mechanical thrombectomy

• Three trials (DEVT, DIRECT-MT, and SKIP) came out in early 2021 that looked for non-inferiority of mechanical thrombectomy (MT) alone when compared to IV tPA+MT (tPA+MT). DEVT and DIRECT-MT hit their non-inferiority targets. SKIP did not. All were completed in Asian populations. Each trial had peculiarities which limited their generalizability and many considered the non-inferiority targets too broad.
• MR CLEAN-NO IV was recently published as a randomized open label trial demonstrating overlapping interquartile results between the tPA+MT vs MT alone group, but did not demonstrate superiority or noninferiority of MT alone.
• Importantly these trials were in endovascular capable centers. Results cannot be generalized to patients who present to a non-thrombectomy capable center.
• Future studies will be aimed at determining subsets of patients that are at higher risk for harm with tPA or higher risk when tPA is withheld
• For now, IV thrombolysis is still the standard of care for all patients presenting within the appropriate window.

IA treatment with thrombolytics after LVO removal?

• Another exciting trial released at #ISC22 was the CHOICE trial, a phase 2b trial conducted in Spain, which showed that intra-arterial (IA) alteplase, when given after successful reperfusion, improved excellent outcomes (mRS 0-1) with no increased risk of bleeding.
• The idea is that residual deficits are caused by microthrombi and residual clot burden and that these might be dissolved with the IA alteplase administration following thrombectomy.
• In the trial, alteplase 0.225mg/kg (max 22.5mg) was either selectively administered to vessels with residual thrombus or non-selectively to the involved side.
• This work will need to be confirmed and replicated before wide-adoption, but this offers another potential way to improve outcomes in the LVO population.

Research in acute ischemic stroke moves quickly, but the general trend continues to be in making thrombectomy more accessible and that exclusions are minimized.

Building more reliable networks and the continuing refinement of triage/transfer processes are other significant areas of research that have the potential to dramatically improve outcomes.  Mobile Stroke Units (MSUs) are another way that stroke care is being transformed.  In 2021, 2 large, controlled clinical trials (B_PROUD and BEST-MSU) demonstrated that as compared with conventional emergency care, treatment in MSUs was safe and resulted in improved functional outcomes in stroke patients.  There is still work to be done to establishing these as a standard care where they are available and to investigate their optimal use and cost effectiveness (PMID 35331008).

For now, mastering each step that you have direct control of at the bedside is the best way frontline providers can save neurons.

For this, see ⬇️: a quick access, downloadable checklist to help you master the Code Stroke!

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Summary and Rapid Reference

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