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  • 1
    Online Resource
    Online Resource
    Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient‐Level Analysis from the EXTEND‐IA Trials, INSPIRE , and SELECT Studies
    Wiley ; 2022
    In:  Annals of Neurology Vol. 91, No. 5 ( 2022-05), p. 629-639
    Details
    In: Annals of Neurology, Wiley, Vol. 91, No. 5 ( 2022-05), p. 629-639
    Abstract: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. Methods In a pooled, patient‐level analysis of 3 randomized controlled trials (EXTEND‐IA, EXTEND‐and IA‐TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90‐day functional independence (modified Rankin Scale [mRS] = 0–2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. Results We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8–19) in EVT versus 10 (6–15) in MM, p   〈  0.001. Pretreatment ischemic core did not differ (EVT = 10 [0–24] ml vs MM = 9 [3–21] ml, p  = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI]  = 1.25–4.67, p  = 0.008, inverse probability of treatment weights [IPTW]‐OR = 1.75, 95% CI = 1.00–3.75, p  = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23–3.29, p  = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12–0.87, p  = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09–4.79, p  = 0.029, IPTW‐OR = 2.02, 1.08–3.78, p  = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p  = 0.17, IPTW‐OR: 0.71, 95% CI = 0.18–2.78, p  = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. Interpretation In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629–639
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v91.5
    DOI: 10.1002/ana.26331
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2037912-2
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  • 2
    Online Resource
    Online Resource
    Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient‐Level Analysis of EXTEND‐IA Trials and SELECT Prospective Cohort
    Wiley ; 2023
    In:  Annals of Neurology Vol. 93, No. 4 ( 2023-04), p. 793-804
    Details
    In: Annals of Neurology, Wiley, Vol. 93, No. 4 ( 2023-04), p. 793-804
    Abstract: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. Methods In a pooled, patient‐level analysis of the EXTEND‐IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. Results A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8–48.4), and median midline shift was 0mm (IQR = 0–2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89–4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (β = −1.19, 95% confidence interval [CI] = −1.51 to −0.88, p   〈  0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23–0.57, p   〈  0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86–3.88, p   〈  0.001) became insignificant (acOR = 1.39, 95% CI = 0.95–2.04, p  = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. Interpretation In this mediation analysis from a pooled, patient‐level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793–804
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v93.4
    DOI: 10.1002/ana.26587
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2037912-2
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  • 3
    Online Resource
    Online Resource
    Thrombectomy Outcomes With General vs Nongeneral Anesthesia : A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Neurology Vol. 100, No. 3 ( 2023-01-17), p. e336-e347
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 3 ( 2023-01-17), p. e336-e347
    Abstract: 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 〉 10 seconds/Tmax 〉 6 seconds (good collaterals – HIR 〈 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 〈 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 〈 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), p interaction : 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 ( p interaction : 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).
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000201384
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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