Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax \u3e 10 seconds/Tmax \u3e 6 seconds (good collaterals - HIR \u3c 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. RESULTS: Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13-22], non-GA: 16 [11-20], DISCUSSION: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score-matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. TRIAL REGISTRATION INFORMATION: EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587)

Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study

Background and Objectives The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) – Tmax \u3e 10 seconds/Tmax \u3e 6 seconds (good collaterals – HIR \u3c 0.4, poor collaterals – HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. Results Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13–22], non-GA: 16 [11–20], p \u3c 0.001) and ischemic core volume (GA: 15.0 mL [3.2–38.0] vs non-GA: 9.0 mL [0.0–31.0], p \u3c 0.001). In addition, GA was associated with longer last known well to arterial access (203 minutes [157–267] vs 186 minutes [138–252], p = 0.002), but similar procedural time (35.5 minutes [23–59] vs 34 minutes [22–54], p = 0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the propensity score–matched pairs, GA was independently associated with worse functional outcomes (adjusted common odds ratio [adj. cOR]: 0.64, 95% CI: 0.44–0.93, p = 0.021) and higher neurologic worsening (GA: 14.9% vs non-GA: 8.9%, aOR: 2.10, 95% CI: 1.02–4.33, p = 0.045). Patients with poor collaterals had worse functional outcomes with GA (adj. cOR: 0.47, 95% CI: 0.29–0.76, p = 0.002), whereas no difference was observed in those with good collaterals (adj. cOR: 0.93, 95% CI: 0.50–1.74, p = 0.82), pinteraction: 0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate (pinteraction: 0.020). Discussion GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score–matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. Classification of Evidence This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. Trial Registration Information EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587)

A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke).

BACKGROUND: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. METHODS: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. RESULTS: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures. CONCLUSIONS: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337

Delayed Functional Independence After Neurothrombectomy (DEFIANT) score: analysis of the Trevo Retriever Registry.

BACKGROUND: Chronological heterogeneity in neurological improvement after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) stroke is commonly observed in clinical practice. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence in patients who do not improve early, is essential for prognostication and rehabilitation. We aim to determine the incidence of early functional independence (EFI) and delayed functional independence (DFI), identify associated predictors after EVT, and develop the Delayed Functional Independence After Neurothrombectomy (DEFIANT) score. METHODS: Demographic, clinical, radiological, treatment, and procedural information were analyzed from the Trevo Registry (patients undergoing EVT due to anterior LVO using the Trevo stent retriever). Incidence and predictors of EFI (modified Rankin Scale (mRS) score 0-2 at discharge) and DFI (mRS score 0-2 at 90 days in non-EFI patients) were analyzed. RESULTS: A total of 1623 patients met study criteria. EFI was observed in 45% (730) of patients. Among surviving non-EFI patients (884), DFI was observed in 35% (308). Younger age (p=0.003), lower discharge National Institutes of Health Stroke Scale (NIHSS) score (p CONCLUSION: Approximately 45% of patients experience EFI. About one-third of non-early improvers experience DFI. Younger age, lower discharge NIHSS score, and absence of any hemorrhage were independent predictors of DFI among non-early improvers

First pass effect in patients with large vessel occlusion strokes undergoing neurothrombectomy: insights from the Trevo Retriever Registry.

BACKGROUND: First pass effect (FPE), defined as near-total/total reperfusion of the territory (modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3) of the occluded artery after a single thrombectomy attempt (single pass), has been associated with superior safety and efficacy outcomes than in patients not experiencing FPE. OBJECTIVE: To characterize the clinical features, incidence, and predictors of FPE in the anterior and posterior circulation among patients enrolled in the Trevo Registry. METHODS: Data were analyzed from the Trevo Retriever Registry. Univariate and multivariable analyses were used to assess the relationship of patient (demographics, clinical, occlusion location, collateral grade, Alberta Stroke Program Early CT Score (ASPECTS)) and device/technique characteristics with FPE (mTICI 2c/3 after single pass). RESULTS: FPE was achieved in 27.8% (378/1358) of patients undergoing anterior large vessel occlusion (LVO) thrombectomy. Multivariable regression analysis identified American Society of Interventional and Therapeutic Neuroradiology (ASITN) levels 2-4, higher ASPECTS, and presence of atrial fibrillation as independent predictors of FPE in anterior LVO thrombectomy. Rates of modified Rankin Scale (mRS) score 0-2 at 90 days were higher (63.9% vs 53.5%, p CONCLUSION: Twenty-eight percent of patients undergoing anterior LVO thrombectomy and 24% of patients undergoing basilar artery occlusion thrombectomy experience FPE. Independent predictors of FPE in anterior circulation LVO thrombectomy include higher ASITN levels, higher ASPECTS, and the presence of atrial fibrillation

A Decade of Improvement in Door‐to‐Puncture Times for Mechanical Thrombectomy But Ongoing Stagnation in Prehospital Care

Background Systems of care surrounding endovascular therapy for stroke have garnered much attention in recent years. In‐hospital metrics, such as “door‐to‐puncture” and procedure times have been areas for quality improvement. The temporal trend and clinical significance of prehospital “onset‐to‐door” time, however, remains unknown. Methods We performed a systematic review of time metric data from all published randomized controlled and investigational device exemption trials involving endovascular therapy for stroke between 2005 and 2019 (n=26). Second, we conducted a record‐level observational analysis on a total of 3512 patients from 3 real‐world registries (Mechanical Embolus Removal in Cerebral Ischemia [MERCI], Thrombectomy REvascularization of Large Vessel Occlusions in Acute Ischemic Stroke [TREVO], and TREVO Stent‐Retriever Acute Stroke [TRACK]), together with 4 prospective trials (MERCI trial, Multi‐MERCI, TREVO‐EU, and TREVO‐2). Only patients receiving mechanical thrombectomy within 9 hours from onset‐to‐puncture time were included. Predictors of good outcome were identified using generalized linear mixed modeling. Results Door‐to‐puncture times (slope=−5.83 min/y; R2=0.25; P=0.046), procedure times (slope=−3.78 min/y; R2=0.54; P<0.001), and onset‐to‐reperfusion times (slope=−11.82 min/y; R2=0.57; P<0.001) improved over the years among previously published randomized controlled trials/investigational device exemption trials from 2005 to 2019. The prehospital metric of onset‐to‐door time, however, remained statistically unchanged (slope=1.03 min/y; R2<0.01; P=0.806). Pooled analysis from record‐level data demonstrated a similar temporal trend where door‐to‐puncture, procedure, and onset‐to‐reperfusion times declined by an average of 12 minutes (R2=0.45; P<0.0001), 6 minutes (R2=0.27; P<0.0001), and 8 minutes per year (R2=0.18; P<0.0001), respectively, over a similar time period. Time from onset to door, however, did not improve (3.6 min/y; R2=0.34; P=0.005). In a backward‐selection regression model, onset‐to‐door time was found to be a significant predictor of patient outcomes, where every hour delay in hospital arrival correlated with a 14% reduction in the odds of a good outcome. Conclusions “Door‐to‐puncture” and procedure times have seen significant improvements over the past decade. The prehospital component of “onset‐to‐door” time, however, has remained stagnant. This presents an unrealized opportunity to enhance patient outcomes through improved systems of care in the prehospital setting

Carotid I's, L's and T's: collaterals shape the outcome of intracranial carotid occlusion in acute ischemic stroke

BACKGROUND: Collaterals may affect revascularization, ischemic severity, and clinical outcomes in acute stroke owing to internal carotid artery (ICA) occlusion. OBJECTIVE: To examine the hypothesis that morphology of occlusive thrombus and collateral flow patterns may influence the outcome of ICA occlusions after mechanical thrombectomy. METHODS: Pooled analyses of ICA occlusions in the MERCI and Multi-MERCI trials employed central angiography review readings to categorize lesions as I, L, or T clots and functional lesions based on collateral flow patterns. Demographic variables, procedural details, and clinical outcomes were compared across ICA lesion types. RESULTS: A total of 72 subjects (mean age 67 years (SD 16), 51% female, median National Institutes of Health Stroke Scale 20 (range 8–35)) were included, with 90-day modified Rankin score ≤2 in 28% and 51% mortality. Clots were categorized as an I lesion in 9/72 (12.5%), L lesion in 12/72 (16.7%), and T lesion in 51/72 (70.8%). Based on collateral flow patterns, cases were categorized as having a functional I lesion in 7/72 (9.7%), functional L in 38/72 (52.8%), and functional T in only 27/72 (37.5%). Multivariate analyses showed that a functional T lesion, with insufficient collateral flow to ipsilateral anterior cerebral arteries via the contralateral ICA, was a strong predictor of both revascularization success and subsequent clinical outcomes. CONCLUSIONS: Collateral flow patterns distinguish the nature and impact of ICA occlusions on expected revascularization and subsequent clinical outcomes in acute ischemic stroke. The nomenclature of terminal ICA occlusions introduced here (carotid I’s, L’s, and T’s) may enhance future endovascular trials targeting such proximal occlusions