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  • Ovid Technologies (Wolters Kluwer Health)  (16)
  • Yassi, Nawaf  (16)
  • 1
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    Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 3 ( 2023-03), p. 706-714
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 706-714
    Abstract: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Methods: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or 〉 50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Results: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%] , adjusted odds ratio [aOR], 2.18 [95% CI, 1.03–4.63] ). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%] , aOR, 3.93 [95% CI, 1.50–10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16–2.06] ; P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00–8.05] versus absent: aOR, 1.98 [95% CI, 0.65–6.03] ; P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%] , aOR, 3.73 [95% CI, 1.25–11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01–3.83] ; P interaction =0.16). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.041061
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 2
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    Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke : A Post Hoc Analysis of the EXTEND-IA TNK Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Neurology Vol. 100, No. 18 ( 2023-05-2), p. e1900-e1911
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 18 ( 2023-05-2), p. e1900-e1911
    Abstract: The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs. Methods We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK. Results Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28–17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44–5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08–0.21) and 0.09 (95% CI 0.04–0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03–0.20) and an sICH rate of 0.07 (95% CI 0.02–0.17) in TNK-treated patients, no significant difference was observed. Discussion Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase. Classification of Evidence This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. Trial Registration Information clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000207138
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 3
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    Response to Late-Window Endovascular Revascularization Is Associated With Collateral Status in Basilar Artery Occlusion
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Stroke Vol. 50, No. 6 ( 2019-06), p. 1415-1422
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 6 ( 2019-06), p. 1415-1422
    Abstract: The benefit of endovascular therapy in extended time windows has been demonstrated in patients with anterior circulation large vessel occlusion ischemic stroke and favorable imaging profile. We evaluated whether collaterals and thrombus burden influence the associations between revascularization, time-to-treatment, and outcome in endovascular therapy-treated patients with basilar artery occlusion. Methods— We retrospectively analyzed clinical and imaging data of consecutive endovascular therapy-treated patients with basilar artery occlusion included in the multicenter Basilar Artery Treatment and Management Collaboration. The BATMAN (Basilar Artery on Computed Tomography Angiography score, which evaluates thrombus burden and collaterals) and the PC-CS (Posterior Circulation Collateral score, which evaluates collaterals) were assessed on computed tomography angiography, blinded to clinical outcome. Good outcome was defined as modified Rankin Scale score of ≤3 within 3 months; revascularization (successful reperfusion) as modified Thrombolysis in Cerebral Infarction 2b–3 (or TIMI [Thrombolysis in Myocardial Infarction] 2–3 in the BASICS [Basilar Artery International Cooperation Study] registry). Results— We included 172 patients with basilar artery occlusion treated with endovascular therapy (124 with mechanical thrombectomy): mean (SD) age 65 (13) years, median National Institutes of Health Stroke Scale 22 (interquartile range 12–30), 64 (37%) treated 〉 6 hours. Revascularization (achieved in 79% of patients) was associated with good outcome ( P =0.003). The use of new generation thrombectomy devices was associated with good outcome ( P =0.03). In patients who achieved revascularization, 29/46 (63%) of patients with a favorable BATMAN score and 26/51 (51%) with favorable PC-CS had good outcomes. In logistic regression analysis (adjusted for age, National Institutes of Health Stroke Scale, and time-to-treatment ≤6/ 〉 6 hours), revascularization was associated with good outcome in patients with favorable BATMAN score (odds ratio, 15.8; 95% CI, 1.4–175; P =0.02) or PC-CS (odds ratio, 9.4; 95% CI, 1.4–64; P =0.02). In patients who achieved revascularization, early (time-to-treatment ≤6 hours) but not late treatment was associated with improved outcome in patients with unfavorable BATMAN score (18/52 [35%]; odds ratio, 15; 95% CI, 1.9–124; P =0.01) or PC-CS (16/44 [36%]; odds ratio, 5.5; 95% CI, 1.4–21; P =0.01). Conclusions— Revascularization is associated with good outcome in patients with basilar artery occlusion with good collaterals and less extensive occlusion, even 〉 6 hours after onset.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.118.023361
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 4
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    Abstract 42: The Effect Of Anesthesia On Thrombectomy Outcomes Is Modified By Collateral Flow: Pooled Patient Level Analysis From EXTEND-IA, EXTEND-IA TNK Part I And II, And SELECT
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. Suppl_1 ( 2022-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: Background: 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 (mRS distribution) were compared between general anesthesia (GA) vs non-general anesthesia (non-GA). Further, we assessed the impact of collateral flow on perfusion imaging evaluated by hypoperfusion intensity ratio (HIR) - Tmax10 sec/Tmax6 sec) on the association between anesthesia type and EVT outcomes. Results: Of 731 treated with EVT, 305 (42%) received GA and 426 (58%) non-GA. The baseline characteristics were similar, except for presentation NIHSS (median [IQR] GA 18 [13-22] , non-GA 16[11-20], p 〈 0.001) and ischemic core volume (GA 14.1mL [3-37] vs non-GA 9mL [0-31] , p=0.002). GA was associated with longer LKW to arterial access (203min [158-267] vs 186min [138-252] , p=0.002), but similar procedural time (36min [23-59] vs 34min [22-54] , p=0.36). Non-GA was independently associated with improved functional outcomes (adj cOR 1.42, 95%CI 1.05-1.93, p=0.024) and lower mortality (17% vs 11.3%, p=0.025). Patients with poor collaterals (HIR≥0.4) had improved functional outcomes with non-GA (adj cOR 1.53, 95%CI 1.02-2.29, p=0.038), while no difference was observed in those with good collaterals-HIR 〈 0.4 (adj cOR 1.38, 95% CI 0.84-2.27, p=0.21). Conclusion: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals. These findings have implications for randomized trials of GA vs non-GA.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.53.suppl_1.42
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 5
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    Microvascular Dysfunction in Blood-Brain Barrier Disruption and Hypoperfusion Within the Infarct Posttreatment Are Associated With Cerebral Edema
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 5 ( 2022-05), p. 1597-1605
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 5 ( 2022-05), p. 1597-1605
    Abstract: Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24–72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy. Methods: We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible ( 〈 1 mm), mild (≥1 to 〈 5 mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere. Results: Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00–1.028), 1.03 (IQR, 1.01–1.077), and 1.15 (IQR, 1.08–1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days ( P 〈 0 .002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 [95% CI, 1.03–1.20], P =0.005; rHV β, 0.39 [95% CI, 0.24–0.55], P 〈 0.0001), as was reduced cerebral blood flow (MLS cOR, 0.25 [95% CI, 0.10–0.58], P =0.001; rHV β, −2.95 [95% CI, −4.61 to −11.29], P =0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 [95% CI, 0.14–0.98], P =0.045; rHV β, −2.59 [95% CI, −4.32 to −0.86], P =0.004). Conclusions: BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.121.036104
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 6
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    Reduced Severity of Tissue Injury Within the Infarct May Partially Mediate the Benefit of Reperfusion in Ischemic Stroke
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. 6 ( 2022-06), p. 1915-1923
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 6 ( 2022-06), p. 1915-1923
    Abstract: Emerging data suggest tissue within the infarct lesion is not homogenously damaged following ischemic stroke but has a gradient of injury. Using blood-brain-barrier (BBB) disruption as a marker of tissue injury, we tested whether therapeutic reperfusion improves clinical outcome by reducing the severity of tissue injury within the infarct in patients with ischemic stroke. Methods: In a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) and EXTEND-IA part-2 (Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke) trials, post-treatment BBB permeability at 24 hours was calculated based on the extent of T1-brightening by extravascular gadolinium on T2* perfusion-weighted imaging and measured within the diffusion-weighted-imaging lesion. First, to determine the clinical significance of BBB disruption as a marker of severity of tissue injury, we examined the association between post-treatment BBB permeability and functional outcome. Second, we performed an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis to estimate the proportion of the reperfusion-outcome relationship that is mediated by change in BBB permeability. Results: In the 238 patients analyzed, an increased BBB permeability measured within the infarct at 24 hours was associated with a reduced likelihood of favorable outcome (90-day modified Rankin Scale score of ≤2) after adjusting for age, baseline National Institutes of Health Stroke Scale, premorbid modified Rankin Scale, infarct topography, laterality, thrombolytic agent, sex, parenchymal hematoma, and follow-up infarct volume (adjusted odds ratio, 0.86 [95% CI, 0.75–0.98]; P =0.023). Mediation analysis suggested reducing the severity of tissue injury (as estimated by BBB permeability) accounts for 18.2% of the association between reperfusion and favorable outcome, as indicated by a reduction in the regression coefficient of reperfusion after addition of BBB permeability as a covariate. Conclusions: In patients with ischemic stroke, reduced severity of tissue injury within the infarct, as determined by assessing the integrity of the BBB, is independently associated with improved functional outcome. In addition to reducing diffusion-weighted imaging-defined infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.121.036670
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 7
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    Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion : A Pooled Analysis of the EXTEND-IA TNK Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Neurology Vol. 98, No. 12 ( 2022-03-22), p. e1292-e1301
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 98, No. 12 ( 2022-03-22), p. e1292-e1301
    Abstract: Detailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion. Methods We performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age ( 〉 80 years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results In patients 〉 80 years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23–5.94) and reduced mortality (acOR 0.34, 95% CI 0.13–0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03–5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg. Discussion TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients. Trial Registration Information NCT02388061, NCT03340493. Classification of Evidence This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients 〉 80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000013302
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 8
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    Utility of Severity-Based Prehospital Triage for Endovascular Thrombectomy : ACT-FAST Validation Study
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 1 ( 2021-01), p. 70-79
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 1 ( 2021-01), p. 70-79
    Abstract: Severity-based assessment tools may assist in prehospital triage of patients to comprehensive stroke centers (CSCs) for endovascular thrombectomy (EVT), but criticisms regarding diagnostic inaccuracy have not been adequately addressed. This study aimed to quantify the benefits and disadvantages of severity-based triage in a large real-world paramedic validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) algorithm. Methods: Ambulance Victoria paramedics assessed the prehospital ACT-FAST algorithm in patients with suspected stroke from November 2017 to July 2019 following an 8-minute training video. All patients were transported to the nearest stroke center as per current guidelines. ACT-FAST diagnostic accuracy was compared with hospital imaging for the presence of large vessel occlusion (LVO) and need for CSC-level care (LVO, intracranial hemorrhage, and tumor). Patient-level time saving to EVT was modeled using a validated Google Maps algorithm. Disadvantages of CSC bypass examined potential thrombolysis delays in non-LVO infarcts, proportion of patients with false-negative EVT, and CSC overburdening. Results: Of 517 prehospital assessments, 168/517 (32.5%) were ACT-FAST positive and 132/517 (25.5%) had LVO. ACT-FAST sensitivity and specificity for LVO was 75.8% and 81.8%, respectively. Positive predictive value was 58.8% for LVO and 80.0% when intracranial hemorrhage and tumor (CSC-level care) were included. Within the metropolitan region, 29/55 (52.7%) of ACT-FAST-positive patients requiring EVT underwent a secondary interhospital transfer. Prehospital bypass with avoidance of secondary transfers was modeled to save 52 minutes (95% CI, 40.0–61.5) to EVT commencement. ACT-FAST was false-positive in 8 patients receiving thrombolysis (8.1% of 99 non-LVO infarcts) and false-negative in 4 patients with EVT requiring secondary transfer (5.4% of 74 EVT cases). CSC bypass was estimated to over-triage 1.1 patients-per-CSC-per-week in our region. Conclusions: The overall benefits of an ACT-FAST algorithm bypass strategy in expediting EVT and avoiding secondary transfers are estimated to substantially outweigh the disadvantages of potentially delayed thrombolysis and over-triage, with only a small proportion of EVT patients missed.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.031467
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 9
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    Abstract 44: Safety Of Tenecteplase And Alteplase In Tandem Lesion Stroke: A Pooled Analysis Of The Extend-IA TNK Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Stroke Vol. 53, No. Suppl_1 ( 2022-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. Suppl_1 ( 2022-02)
    Abstract: Introduction: The efficacy of tenecteplase (TNK) in patients with tandem lesions (TL) in the anterior circulation is unknown. The longer half-life of TNK could potentially lead to increased hemorrhage, especially in patients who require stenting of the extracranial internal carotid artery (eICA) and subsequent antiplatelet therapy. We assessed the efficacy and safety of TNK in a pooled analysis of the EXTEND-IA TNK trials. Methods: We compared the treatment effect of TNK (pooled analysis of 0.25 and 0.40mg/kg dosing) with alteplase (tPA), stratifying for TL presence. A TL was defined as a combination of eICA pathology (ipsilateral stenosis 〉 70% or occlusion) and intracranial LVO. Outcomes evaluated include 90-day mRS, intracranial reperfusion at initial angiographic assessment, mortality, ICH (symptomatic [sICH] and parenchymal hematoma [PH] ). Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results: Of 483 patients with an anterior circulation occlusion, 71/483 (15%) patients had a TL and 43/71 (61%) patients required eICA stenting. In TL patients, reperfusion at initial angiographic assessment was observed in 11/56 (20%) of patients treated with TNK vs. 1/15 (7%) patients treated with tPA (aOR:3.71; 95% CI:0.42-32.75). sICH was observed in 4/71(6%) TL vs 7/412 (2%) nonTL patients (p=0.04). Among TL patients, sICH occurred in 4/56 (7%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.57); sICH occurred in 2/40 (5%) of the 0.25mg/kg TNK group and 2/16 (12.5%) of the 0.40mg/kg TNK group. PH was observed in 6/56 (11%) patients treated with TNK vs 0/15 (0%) tPA treated patients (p=0.33). 90-day mRS (TNK median 2 vs. tPA median 4, acOR:1.21; 95% CI:0.42-3.48), mortality (TNK: 5 [9%] vs. tPA: 3 [20%] , aOR:0.45; 95% CI:0.08-2.50), and eICA stenting (TNK: 35 [64%] vs. tPA: 8 [57%] , p=0.65) rates did not differ between the two treatment groups. Conclusions: Although patients with TL in the anterior circulation were at higher risk of hemorrhagic complications, these did not significantly differ between the TNK and tPA groups. A numeric increase in bleeding with TNK was not accompanied by an increase in mortality or worse functional outcome.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.53.suppl_1.44
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 10
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    Abstract 92: Tenecteplase Treatment And Thrombus Characteristics Associated With Early Reperfusion - An EXTEND-IA TNK Trials Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. Suppl_1 ( 2023-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Background: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trials. Methods: Patients with large vessel occlusion (LVO) were randomized to treatment with tenecteplase (0.25mg/kg or 0.4mg/kg) or alteplase (0.9mg/kg) prior to thrombectomy. The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or 〉 50% reperfusion on initial angiographic assessment. We compared the treatment effect of tenecteplase versus alteplase overall, and in subgroups based on intracranial occlusion site, the presence of contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores), whilst adjusting for relevant covariates using mixed effects logistic regression models. Results: Among the 465 patients in the primary analysis, early reperfusion occurred in 18% (84/465). Tenecteplase was associated with a higher odds of early reperfusion (tenecteplase: 75/369 [20%] vs. alteplase: 9/96 [9%] , aOR: 2.18 [95%CI: 1.03-4.63]). The difference between thrombolytics was most notable in distal M1 or M2 occlusions (tenecteplase: 53/176 [30%] vs. alteplase: 4/42 [10%], aOR: 3.73 [95%CI: 1.25-11.11] ), thrombi with contrast permeability (tenecteplase: 38/160 [24%] vs. alteplase: 5/48 [10%] , aOR: 2.83 [95%CI: 1.00-8.05]), and in low clot burden occlusions (tenecteplase: 66/261 [25%] vs. alteplase: 5/67 [7%], aOR: 3.93 [95%CI: 1.50-10.33] ). Both thrombolytics had limited early reperfusion efficacy in proximal occlusions (ICA: tenecteplase 1/73 [1%] vs. alteplase 1/19 [5%] ) and in high clot burden occlusions (tenecteplase: 9/108 [8%] vs. alteplase: 4/29 [14%] , aOR: 0.58 [95%CI: 0.16-2.06]). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in distal LVO, in contrast-permeable thrombi, and in lesions with low clot burden. Reperfusion efficacy remains limited in ICA occlusions and lesions with high clot burden. Further improvements in intravenous thrombolytics are required.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.54.suppl_1.92
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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