Mechanical thrombectomy for acute ischemic stroke
Mechanical thrombectomy with a stent retriever is recommended when all criteria met (Level I 1)):
● prestrokemodified Rankin Scale (mRS) of 0–1
● causative occlusion of ICA or M1 segment of MCA
● age ≥ 18 years
● NIHSS score ≥ 6
● ASPECTS ≥ 6
● treatment can be initiated (groin puncture) ≤ 6 hours of onset Benefits uncertain, but mechanical thrombectomy may be reasonable for (Level II 2))
● carefully selected patients with causative occlusion of M2 or M3 segment of MCA, or anterior cerebral, vertebral, basilar or posterior cerebral arteries
● or pre-stroke mRS > 1, ASPECTS < 6 and causative occlusion of ICA or M1 segment; however, additional randomized trials are needed
● when treatment can be initiated (groin puncture) ≤ 6 hours after onset
Mechanical thrombectomy is recommended for selected patients 6–16 hours from onset with large vessel occlusion (LVO) in the anterior circulation who meet other DAWNa or DEFUSE-3a eligibility criteria (Level I 3)).
Mechanical thrombectomy is reasonable in selected patients 16–24 hours from onset with anterior circulation LVO who meet other DAWNa eligibility criteria (Level II 4)).
The goal of thrombectomy should be reperfusion to a mTICI 2b/3 angiographic result and to minimize the time to treatment in order to maximize the chances of good functional outcome (Level I 5)) a DAWN 6) & DEFUSE-3 7) are the only randomized controlled trials that showed a benefit of mechanical thrombectomy > 6 hours from onset. CTP, DW-MRI or MRI perfusion can aid in patient selection when RCT eligibility criteria are strictly met. Trial eligibility can be found online at http://stroke.aha- journals.org/lookup/suppl/doi:10.1161/STR.0000000000000158/-/DC1 DEFUSE-3 used perfusion/core mismatch & maximum core size (< 70 ml) to select patients 6–16 hrs from onset. Proprietary software (such as iSchemaView’s RAPIDTM) can quickly analyze scans to determine the mismatch. DAWN: used clinical/imaging mismatch (combination of NIHSS score and imaging findings on CTP or DWI-MRI) to select patients 6–24 hrs from the onset.
The indications for mechanical thrombectomy (MT) have expanded since the American Heart Association/American Stroke Association (AHA/ASA) published its first guideline on MT in 2013. Multiple subsequent randomized clinical trials of MT have proven its efficacy, including the DAWN and DEFUSE 3 trials. The current guideline from AHA/ASA provides Class I support for the use of MT for the following indications:
1. Internal carotid artery occlusion/M1 Middle Cerebral Artery (MCA) occlusion, <6h, National Institutes of Health Stroke Scale (NIHSS) score ≥6, Alberta Stroke Program Early CT Score (ASPECTS) ≥6;
2. Large vessel occlusions (LVO) in the anterior circulation, between 6-16h, and meet DAWN or DEFUSE 3 eligibility criteria. There is also Class IIa evidence for the use of MT for LVO in the anterior circulation, 16-24h, that meet other DAWN eligibility criteria. In clinical practice, these Class I and IIa indications for MT are well followed; however, there are many other potential indications such as 1. M2 or M3 MCA occlusion, < 6 hours; 2. ASPECTS <6, ICA or M1 MCA occlusion, <6 hours;
3. NIHSS score <6, ICA or M1 occlusion , <6 hours;
4. Tandem occlusions;
5. Posterior circulation occlusion < 6 hr. 8).
The use of mechanical thrombectomy in the management of acute ischemic stroke is becoming increasingly popular.
see Mechanical thrombectomy for large vessel occlusion.
The benefits of mechanical thrombectomy for emergent large vessel occlusion (ELVO) have been established. Combined mechanical/aspiration (Solumbra) and a direct aspiration as a first pass technique (ADAPT) are valid procedures requiring an intermediate catheter for clot suction. SOFIA (Soft torqueable catheter Optimized For Intracranial Access) was developed as a single lumen flexible catheter with coil and braid reinforcement.
The effectiveness of mechanical thrombectomy was confirmed in several randomised clinical trials conducted at University at Buffalo and elsewhere by a team of researchers including Elad Levy. 9)
The reported superiority of mechanical thrombectomy to intravenous thrombolytics has jettisoned endovascular intervention into the forefront of acute ischemic stroke (AIS) management. These successes have allowed a chance for recanalization for patients not meeting the strict eligibility criteria for intravenous thrombolytics. Retrievable Stents and aspiration have emerged as two of the most popular and effective approaches for AIS thrombectomy. Since the beginning of mechanical thrombectomy with the Merci device (Stryker) and first-generation Penumbra aspiration system (Penumbra Inc), contemporary techniques have demonstrated reliable recanalization and improved clinical outcomes 10)
Patients in the positive trials were treated at hospitals with complex, efficient, resource-rich, team-based stroke systems in place. To ensure attainment of trial results in actual practice, patients should receive treatment at facilities certified as having the resources, personnel, organization, and continuous quality improvement processes characteristic of trial centers. It is our hope that, through greater education initiatives, robust resource investment, and developing quality-based certification processes, the results demonstrated by these trials may be extrapolated to greater numbers of centers - in turn allowing greater access for patients to high-quality, advanced stroke care 11).
Endovascular thrombectomy (ET) is the standard of care for treatment of acute ischemic stroke (AIS) secondary to large vessel occlusion.
Endovascular thrombectomy (EVT) achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group 12).
Endovascular thrombectomy has become the gold standard for acute ischemic stroke intervention in appropriate patients. Occasionally, thrombectomy through the standard craniocervical artery related to the affected territory is not technically feasible due to patient specific anatomical issues.
Thrombectomy across the Circle of Willis is a potential bailout technique for select, complex cases. Further investigation is warranted 13).
Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms. Methods We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90. Results The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18).
Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .) 14).
Intravenous recombinant tissue plasminogen activator had been the only approved treatment for acute ischemic stroke since its approval in 1995. However, the restrictive time window, numerous contraindications, and its low recanalization rate were all limitations of this modality. Under those circumstances, endovascular stroke therapy went through a great evolution during the past two decades of intravenous thrombolysis. The results of the 2013 randomized trials for endovascular stroke therapy were neutral, although they were limited by insufficient imaging screening at enrollment, early-generation devices with less efficacy, and treatment delays. Huge progress was made in 2015, as there were five randomized clinical trials which all demonstrated the safety and efficacy of endovascular stroke treatment. Despite differences in detail patient enrollment criteria, all 5 trials employed key factors for good functional recovery; (1) screening with non-invasive imaging to identify the proximal occlusion and exclude a large infarct core, (2) using highly effective modern thrombectomy devices mainly with stent retriever, and (3) establishment of a fast workflow to achieve effective reperfusion. The results of those trials indicate that modern thrombectomy devices can allow for faster and more effective reperfusion, which can lead to improved clinical outcomes compared to intravenous thrombolysis alone. These advances in mechanical thrombectomy are promising in the global fight against ischemic stroke-related disability and mortality. Two current mainstreams among such mechanical thrombectomy techniques, “stent retriever thrombectomy” and “direct clot aspiration”, are the topic of this review. Stent retriever thrombectomy using Solitaire and Trevo retriever will be firstly discussed. And, the commonalities and the differences between two major clot aspiration thrombectomy techniques; a direct aspiration first pass technique (ADAPT) and forced arterial suction thrombectomy (FAST), will be additionally explained. Finally, details regarding the combination of direct clot aspiration and stent retriever thrombectomy, the switching strategy and the Solumbra technique, will be described 15).
Primary suction thrombectomy produced higher recanalization and good clinical outcome rates than did stent retriever thrombectomy. Larger-scale studies are necessary that consider factors such as occlusion site, stroke severity, and concomitant use of endovascular devices 16).
Case series
A multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR.
Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR.
In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women 17).
Javed et al. included all eligible adult acute ischemic stroke (AIS) patients treated with endovascular thrombectomy (EVT) at the Montefiore Medical Center from June 2016 to January 2020. Data was systematically collected via chart review including pre-, intra- and post-procedural variables. The outcome was the Modified Rankin Scale (mRS) at 90 days post-EVT where a poor outcome was defined as mRS 3-6: 3-5 for functional dependency and 6 for death. Model selection methods including stepwise and Lasso were evaluated via cross-validation where the final multivariable logistic regression model was chosen by optimizing the Area Under the Receiver Operating Characteristic Curve (ROC AUC).
They included 224 patients (mean age: 65 years old, male: 55%, 90-day poor outcome: 60%). The final model achieved a median AUC of 0.84, IQR: (0.80, 0.87). A 7-point score, called Bronx Endovascular Thrombectomy (BET) score, was developed with more points indicating higher likelihood of 90-day poor outcome (0 point: ≤21% risk; 1-2: 24%; 3: 61%; 4: 86%; 5: 96%; 6-7: ≥99%). One point was awarded for the following variables: current smoker, diabetic, general anesthesia received, puncture to perfusion time ≥45 minutes, and Thrombolysis in Cerebral Infarction (TICI) score <3. Two points were awarded for a post-EVT National Institute of Health Stroke scale (NIHSS) of ≥10.
Incorporating peri-procedural data they developed the competitive BET score predicting 90-day functional dependency and death, which may help providers, patients and caregivers manage expectations and organize early rehabilitative services 18).
Strokes in patients aged ≥80 years are common, and advanced age is associated with relatively poor poststroke functional outcome. The current guidelines do not recommend an upper age limit for endovascular thrombectomy (EVT). The purpose of this study is to evaluate the effectiveness of EVT in acute stroke because of large vessel occlusion for elderly patients >age 80 years. Methods- A Markov decision analytic model was constructed from a societal perspective to evaluate health outcomes in terms of quality-adjusted life years (QALYs) after EVT for acute ischemic stroke because of large vessel occlusion in patients above age 80 years. Age-specific input parameters were obtained from the most recent/comprehensive literature. Good outcome was defined as a modified Rankin Scale score ≤2. Probabilistic, 1-way, and 2-way sensitivity analyses were performed for both healthy patients and patients with disability at baseline. Results- Base case calculation showed in functionally independent patients at baseline, intravenous thrombolysis (IVT) with tPA (tissue-type plasminogen activator) only to be the better strategy with 3.76 QALYs compared to 2.93 QALYs for patients undergoing EVT. The difference in outcome is 0.83 QALY (equivalent to 303 days of life in perfect health). For patients with baseline disability, IVT only yields a utility of 1.92 QALYs and EVT yields a utility of 1.65 QALYs. The difference is 0.27 QALYs (equivalent to 99 days of life in perfect health). Multiple sensitivity analyses showed that the effectiveness of EVT is significantly determined by the morbidity and mortality after both IVT and EVT strategies, respectively. Conclusions- Our study demonstrates the impact of relevant factors on the effectiveness of EVT in patients above 80 years of age. Morbidity and mortality after both IVT and EVT strategies significantly influence the outcomes in both healthy and disabled patients at baseline. Better identification of patients not benefiting from IVT would optimize the selective use of EVT thereby improving its effectiveness 19).
Outcome
Mechanical thrombectomy (MT) became a standard of care for stroke patients after the positive results of five randomized trials in 2015. However, elderly patients > 65 were excluded from those trials. Recent studies and clinical trials examining the efficacy of MT in patients over the age of 85 have shown that good outcomes can be achieved with careful patient selection.
Modern MT in elderly patients with acute ischemic stroke is safe and effective compared to younger patients despite a lower favorable clinical outcome. Findings may suggest that an appropriate MT strategy with respect to the location of the target occlusion and vascular tortuosity might be helpful to achieve fast reperfusion and improved outcomes for elderly patients 20).
NIHSS score <10 at 24 hours after stroke onset is a strong predictor of favorable outcomes at 90 days in patients treated with mechanical thrombectomy 21).